Selected Poster Abstracts from MauiDerm for Dermatologists 2019

A message from the Guest Editor and MauiDerm Program Director, George Martin, MD

Dear Colleagues:

The 2019 edition of the MauiDerm for Dermatologists meeting had a variety of clinical and scientific data presented not only at the podium, but in its poster sessions as well. A wide range of clinically relevant material was presented in poster format. For those of you who were not on hand to review the posters and discuss them with their authors, we have compiled and indexed selected posters from the 2019 meeting. It is my hope that you will find the posters informative and thought provoking.

With aloha,

George Martin, MD

MauiDerm 2019 Program Director; Guest Editor, The Journal of Clinical and Aesthetic Dermatology

J Clin Aesthet Dermatol. 2019;12(5 Suppl):S8–S35

Funding for this supplement was provided by Celgene Corporation.

CONTENT

ACNE

Clinical development of clascoterone (cortexolone 17?-propionate, CB-03-01), 1% cream for the treatment of acne vulgaris
FMX101 4% topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: efficacy and safety from a Phase III randomized, double-blind, vehicle-controlled study
Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris: assessment of safety and tolerability in subgroups
Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a preadolescent population
Safety and efficacy of clascoterone (cortexolone 17? propionate, CB-03-01), 1% cream for the treatment of acne vulgaris: summary of early phase study results

AESTHETICS

Diluted and hyperdiluted calcium hydroxylapatite (Radiesse®) for skin tightening: guidelines from a global consensus panel
Efficacy, safety, and durability of collagenase clostridium histolyticum for the treatment of edematous fibrosclerotic panniculopathy (cellulite)
Escalating doses of incobotulinumtoxinA for extended treatment of glabellar frown lines: Safety and efficacy results from a randomized, double-blind study
A multicenter, open-label, prospective study of cannula injection of large-gel particle hyaluronic acid with lidocaine for cheek augmentation and the correction of age related midface contour deficiencies
Multicenter pivotal study of the safety and effectiveness of Cellfina® for the treatment of cellulite—Five-year update
Multicenter pivotal study of the safety and effectiveness of a tissue stabilized-guided subcision procedure for the treatment of cellulite—Fiver-year update
Optimizing patient outcomes through a customized approach of microfocused ultrasound with visualization treatments: consensus guidelines
A prospective, multicenter, randomized, evaluator-blinded, split-hand study to evaluate the effectiveness and safety of large-gel particle hyaluronic acid with lidocaine for the correction of volume deficits in the dorsal hand
Understanding the Hispanic/Latino facial aesthetic patient

ATOPIC DERMATITIS

Dupilumab efficacy and safety in adolescents with moderate-to-severe atopic dermatitis: results from a multicenter, randomized, placebo-controlled, double-blind, parallel-group, Phase III study
Efficacy and safety of upadacitinib treatment over 32 weeks for patients with atopic dermatitis from a Phase IIb, randomized, placebo-controlled trial
GBR 830 induces progressive and sustained improvements in atopic dermatitis skin biomarkers and clinical parameters
Patient-reported outcomes in subjects with atopic dermatitis treated with tapinarof cream: results from a Phase IIb, randomized parallel-group study
Primary results from a Phase IIb, randomized, placebo-controlled trial of upadacitinib for patients with atopic dermatitis
Tralokinumab significantly reduces Staphylococcus aureus colonization in adult patients with moderate-to-severe atopic dermatitis: results from a Phase IIb, randomized, double-blind, placebo-controlled study

CUTANEOUS ONCOLOGY

Improvement of risk assessment in cutaneous melanoma (CM) by a prognostic 31-gene expression profile (31-GEP) test over AJCC-based staging alone
Phase II study of cemiplimab, a human monoclonal anti-PD-1 antibody, in patients with advanced basal cell carcinoma (BCC) who experienced progression of disease on, or were intolerant of, prior hedgehog pathway inhibitor (HHI) therapy
Primary analysis of Phase II results for cemiplimab, a human monoclonal anti-PD-1 antibody, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC)

HYPERHYDROSIS

Clinical management of anticholinergic adverse events with topical glycopyrronium tosylate, a treatment for primary axillary hyperhidrosis
Short- and long-term efficacy and safety of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: post hoc pediatric subgroup analyses from the Phase III studies

PRURITUS

Impact of serlopitant on prurigo nodularis measured by the prurigo activity score

PSORIASIS

Effects of brodalumab on anxiety and depression in patients with psoriasis: results from a Phase III, randomized, controlled clinical tri al
Efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis of the scalp: results of a Phase III, multicenter, randomized, placebo-controlled, double-blind study
Efficacy and safety of an oral, selective TYK2 inhibitor, BMS-986165, in patients with moderate-to-severe plaque psoriasis: a Phase II, randomized, placebo-controlled trial
Efficacy of risankizumab compared with placebo across subgroups in patients with moderate-to-severe plaque psoriasis: integrated analyses from three Phase III trials
Efficacy of tildrakizumab in patient subgroups across one Phase IIb and two Phase III trials in patients with moderate-to-severe chronic plaque psoriasis
An evaluation of clinical and quality-of-life outcomes with apremilast treatment in clinical studies in patients with moderate-to-severe (ESTEEM) or moderate (UNVEIL) plaque psoriasis and scalp or nail involvement
An evaluation of clinical and quality-of-life outcomes with apremilast treatment for up to 52 weeks in ESTEEM 1 patients with moderate-to-severe plaque psoriasis classified as PASI-75 nonresponders
Impact of prior treatment history on efficacy of risankizumab compared with placebo in patients with moderate-to-severe plaque psoriasis: integrated analyses from three Phase III trials
Incidence of cardiovascular events among tildrakizumab-treated patients with moderate to severe plaque psoriasis: pooled data from 3 large randomized clinical trials
Incidence of infections in clinical trials of tildrakizumab for moderate-to-severe chronic plaque psoriasis
Insights into psoriasis disease severity and treatment efficacy using patient-level Psoriasis Area and Severity Index (PASI) scores from tildrakizumab Phase III clinical trials
Long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion
Maintenance of response with guselkumab for up to three years’ treatment in the Phase III VOYAGE 1 trial of patients with plaque psoriasis
No increased risk of liver dysfunction from tildrakizumab treatment: post-hoc analyses of the tildrakizumab psoriasis clinical program
An open-label, observational study evaluating calcipotriene/betamethasone dipropionate foam in psoriasis patients being treated with biologic agents
Outcomes of pregnancies from tildrakizumab Phases I to III clinical development program
Patient-reported outcomes in subjects with plaque psoriasis treated with tapinarof cream: results from a Phase IIb, randomized parallel-group study
Physician Global Assessment and body surface area composite tool response in patients with plaque psoriasis after 16 and 48 weeks of certolizumab pegol treatment
Rapid and effective itch relief using calcipotriol plus betamethasone dipropionate foam in patients with psoriasis
Response to mirikizumab at Week 52 among patients who did not achieve a PASI 90 response at Week 16
Safety and efficacy of a fixed combination halobetasol and tazarotene lotion in the treatment of moderate-to-severe plaque ssoriasis: subgroup analysis
Safety and efficacy of halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis: a pooled analysis of two Phase III studies
Secukinumab improves GRAPPA-OMERACT core domains of psoriatic arthritis
Secukinumab provides rapid relief from pain and itch in patients with moderate-to-severe psoriasis: diary data from pooled ERASURE and FIXTURE studies
Secukinumab rapidly improves mobility, self-care, and usual activities in patients with psoriasis: pooled analysis from four Phase III trials

ROSACEA

Combined doxycyclin 40mg modified release capsules plus ivermectin 1% cream therapy for severe papulopustular rosacea
Efficacy and safety of FMX103 (1.5% minocycline foam) in the treatment of moderate-to-severe papulopustular rosacea: results from two Phase III randomized, multicenter, double-blind, vehicle-controlled studies

SEBORRHEIC KERATOSES

Assessing patient satisfaction with hydrogen peroxide topical solution, 40% (w/w) treatment of seborrheic keratoses on the face, neck, and décolletage: objectives and design of the Phase IV, open-label SK-FAN study
Safety of hydrogen peroxide topical solution 40% (w/w) in patients with skin of color and seborrheic keratoses: pooled analysis of two Phase III, randomized, double-blind, vehicle-controlled, parallel-group studies

ACNE

Clinical development of clascoterone (cortexolone 17alpha-propionate, CB-03-01) 1% cream for the treatment of acne vulgaris

Presenters: Mazzetti A, Moro L, Gerloni M, Rosette C, Fragasso E, Cartwright M

Affiliations: Cassiopea SpA, Milan, Italy

Background/Objective: Two Phase III investigations of clascoterone (CB-03-01) cream 1% for the treatment of moderate-to-severe acne vulgaris in individuals nine years of age or older recently concluded. The cream’s active ingredient is clascoterone (cortexolone 17alpha-propionate). Clascoterone is a novel, topical androgen receptor (AR) inhibitor whose chemical structure is characterized by a fused, four-ring backbone that is identical to dihydrotestosterone (DHT). It competes with DHT and selectively targets androgen receptors in sebocytes and hair papilla cells within the skin’s pilosebaceous unit (PU). By competing with DHT for AR binding, clascoterone affects multiple acnegenic pathways. Clascoterone selectively binds to AR with high affinity at the site of application and inhibits DHT-stimulated signaling downstream of the AR, exerting a strong antagonistic effect on both sebum (lipid) production and downstream AR activation of inflammatory pathways.

Methods: Clascoterone cream 1% for acne vulgaris investigations included a Phase I single-dose pharmacokinetics (PK) study with 24 healthy volunteers; a randomized, double-blind, vehicle-controlled, single-ascending dose Phase I repeat dose PK study with 24 healthy volunteers; a Phase I steady state PK study with eight subjects with acne vulgaris; a single-center, open-label, pilot, six-week repeat-dose Phase I three-week cumulative skin irritation study with 36 healthy volunteers; a Phase I repeat insult patch test in 202 healthy subjects administered 10 patch applications with vehicle and saline (negative) controls; a Phase II hypothalamic-pituitary-adrenal (HPA)/PK study with 42 subjects with acne vulgaris; an open-label, 14-day repeat-dose Phase II proof-of-concept study with 72 adult subjects with facial acne vulgaris; a randomized, double-blind, vehicle-controlled, active-comparator, tretinoin 0.05% cream, eight-week repeat-dose Phase II dose-escalating study with 363 subjects with facial acne vulgaris; and a multicenter, randomized, double-blind, vehicle controlled, 12-week repeat-dose, evaluation of clascoterone cream (0.1% twice per day [BID], 0.5% BID, 1% daily [QD], or 1% BID) versus vehicle with about 90 subjects per cohort over 12 weeks in subjects with facial acne vulgaris.

Results: The five Phase I studies (n=294) affirmed that topical application of the 1% cream is well tolerated with no measurable systemic side effects. The active ingredient permeates the skin to the dermal levels, with cortexolone 17alpha-propionate and metabolites quantifiable at low plasma levels. The three Phase II studies (n=477) revealed minimal systemic absorption; the active ingredient works locally within the hair follicle. Subjects did not show clinical evidence of adrenal suppression under maximal use conditions. Local side effects were mostly mild. The 1% cream BID, determined to be the ideal concentration and delivery, was selected for the subsequent Phase III clinical trials.

Conclusion: Results of the aforementioned studies have demonstrated that clascoterone cream 1% selected for clinical development is well-tolerated locally, results in minimal systemic exposure when applied topically, has a clinical safety profile similar to the vehicle, and is significantly more effective than the vehicle at reducing inflammatory and noninflammatory lesion counts in adolescents and adults.

FMX101 4% topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: efficacy and safety from a Phase III randomized, double-blind, vehicle-controlled study

Presenters: Raoof J¹, Hooper D², Moore A³, Zaiac M⁴, Sullivan T⁵, Kircik L⁶, Lain E⁷, Jankicevic J⁸, Stuart I⁸

Affiliations: ¹Encino Research Center, Encino, CA; ²Delricht Research, New Orleans, LA; ³Arlington Research Center, Arlington, TX; ⁴Sweet Hope Research Specialty, Inc., Miami Lakes, FL; ⁵Sullivan Dermatology, North Miami Beach, FL; ⁶Icahn School of Medicine at Mount Sinai, New York, NY; ⁷Austin Institute for Dermatology, Austin, TX; ⁸Foamix Pharmaceuticals, Inc, Bridgewater, NJ

Background/Objective: Acne vulgaris is a prevalent chronic inflammatory skin disorder that can affect a majority of the population at some point during their life. Oral minocycline and doxycycline are considered first-line therapies for the treatment of moderate-to-severe acne, but are associated with potentially serious systemic side effects. FMX101 4% is the first stable topical foam formulation of minocycline that has been shown to be an effective and well-tolerated treatment for acne. In addition to a Phase II clinical trial and two double-blind Phase III pivotal studies, a third Phase III study (FX2017-22) was conducted to further evaluate the efficacy and safety of daily topical administration of FMX101 4% versus vehicle foam for a period of 12 weeks for the treatment of moderate-to-severe acne vulgaris.

Methods: FX2017-22, a Phase III multicenter (89 sites), randomized, double-blind, vehicle-controlled, two-arm study, further evaluated the efficacy and safety of topical FMX101 4% in the treatment of moderate-to-severe acne vulgaris. Subjects were randomized 1:1 to receive FMX101 4% or vehicle foam. Foam was self-applied once-daily for 12 weeks.

Results: In total, 1,507 subjects were enrolled in the study. At Week 12, subjects treated with FMX101 4% had a statistically significantly greater reduction in the number of inflammatory lesions from baseline compared with the vehicle treatment group, p<0.0001. At Week 12, the proportion of subjects achieving Investigator’s Global Assessment (IGA) treatment success in the FMX101 4% treatment group was statistically significantly higher than in the vehicle treatment group, p<0.0001. At Week 12, the absolute change in noninflammatory lesion count in the FMX101 4% treatment group was statistically significantly greater than in the vehicle treatment group, p<0.01. The percentage reduction in inflammatory lesions was statistically significantly greater for FMX101 4% versus vehicle at Weeks 3, 6, 9, and 12.

Conclusion: The results of the Phase III study showed that FMX101 4% was safe and effective for the treatment of moderate-to-severe acne. The study met both coprimary endpoints of absolute change from baseline in inflammatory lesion count and proportion with IGA treatment success at Week 12. We observed a significant reduction in the number of inflammatory and noninflammatory lesions at Week 12 from baseline in FMX101 4% treatment group versus vehicle treatment group. We also observed significant improvement in IGA treatment success at Week 12 in FMX101 4% treatment group versus vehicle treatment group. The safety profile of FMX101 was found to be consistent with that determined from the two prior Phase III studies (FX2014-04 and FX2014-05).

Funding/Disclosures: This study was funded by Foamix Pharmaceuticals. JR, DH, MZ, TS, and EL served as investigators for Foamix. AM is an investigator, consultant, and/or speaker for Abbvie, Aclaris, Actavis, Astellas, Asubio, Biofrontera, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, Coherus, Dermavant, Dermira, Eli Lilly, Foamix, Galderma, Incyte, Janssen, Leo, Mayne, Novartis, Parexel, Pfizer, Therapeutics, and Verrica. LK is an investigator and consultant for Foamix. JJ is a consultant for Foamix Pharmaceuticals. IS is an employee of Foamix Pharmaceuticals.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris: assessment of safety and tolerability in subgroups

Presenters: Zeichner JA¹, Harper JC², Roberts WE³, Guenin E⁴, Bhatt V⁵, Pillai R⁵

Affiliations: ¹Mount Sinai Hospital, New York, NY; ²The Dermatology and Skin Care Center of Birmingham, Birmingham, AL; ³Generational and Cosmetic Dermatology, Mirage, CA; ⁴Ortho Dermatologics, Bridgewater, NJ; ⁵Dow Pharmaceutical Sciences Inc., Petaluma, CA

Background/Objective: Topical tretinoin has been studied extensively in clinical trials, and its essential role in the treatment of acne vulgaris has been established through evidence-based guidelines. However, there is a common perception that its use is associated with significant cutaneous irritation and the potential to cause or exacerbate postinflammatory hyperpigmentation (PIH) in patients who are especially vulnerable (e.g., Hispanic and African-American patients). A novel tretinoin 0.05% lotion was developed using polymerized emulsion technology to provide both improved efficacy and tolerability. The objective was to evaluate the safety and tolerability of this novel tretinoin 0.05% lotion for the treatment of moderate-to-severe acne.

Methods: A total of 1,640 patients, 9 to 58 years of age, were randomized to receive a novel tretinoin 0.05% lotion or vehicle in two double-blind, placebo-controlled 12-week, two-arm, parallel-group studies evaluating safety and efficacy. Cutaneous safety (erythema and scaling) and tolerability (itching, burning, and stinging) were assessed using a scale from 0 (none) to 3 (severe). Safety was evaluated through reported adverse events (AEs), which were summarized by treatment group, severity, and relationship to study treatment.

Results: Across the two studies, tretinoin 0.05% lotion was considered safe and well tolerated. The most commonly reported treatment-related AEs were of low incidence and included application site reactions and skin-related events attributed to the known properties of tretinoin. Only application site pain (3.1%), dryness (3.7%), and erythema (1.4%) were reported by more than one percent of patients. Skin reactions, such as scaling, burning, and stinging, were rare, mild, and transient. Application site reaction scores were lower than those reported in studies with other tretinoin formulations (e.g., microsphere, gel), even in patients known to be more susceptible to irritation, such as children and women (incidence 1.4% and 1.2%, respectively). In patients where PIH might be more of a concern than the acne that precedes it, mean baseline scores were reduced with treatment. A limitation of the study was that this subgroup analysis is post hoc.

Conclusion: This novel tretinoin 0.05% lotion developed using polymerized emulsion technology provides a highly favorable safety and tolerability profile in patients with moderate-to-severe acne.

Funding/Disclosures: JAZ, JCH, and WER are advisors to Ortho Dermatologics. EG, VB, and RP are employees of Bausch Health.

Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a preadolescent population

Presenters: Eichenfield LF¹, Sugarman JL², Guenin E³, Bhatt V⁴

Affiliations: ¹Departments of Dermatology and Pediatrics; University of California, San Diego School of Medicine and Rady Children’s Hospital, San Diego, CA; ²University of California, San Francisco, CA; ³Ortho Dermatologics, Bridgewater, NJ; ⁴Dow Pharmaceutical Sciences Inc., Petaluma, CA

Background/Objective: Acne vulgaris is one of the most common skin conditions in children and adolescents. The efficacy of tretinoin is well documented in large pivotal studies that included pediatric patients ranging from 12 to 18 years of age. With acne routinely presenting in patients younger than 12 years, data are needed in a younger age group. Lotion formulations are commonly prescribed by dermatologists and are well-liked by patients. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat patients with acne who might be sensitive to the irritant effects of other tretinoin formulations. The objective was to evaluate the safety and efficacy of a novel once-daily application of a tretinoin 0.05% lotion in preadolescent patients 13 years of age or younger with moderate-to-severe acne.

Methods: The study was a post-hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase III studies in moderate or severe acne. Preadolescent patients aged 9 to 13 years (N=154) were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle once daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear rating). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout.

Results: At Week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 49.5 percent and 44.0 percent, respectively, compared with 31.4 percent and 18.8 percent with vehicle (both P=0.001). Treatment success was achieved by 23.7 percent of patients in the tretinoin group by Week 12, compared to 7.2 percent in the vehicle group (P=0.009). The majority of AEs were mild and transient. There were no serious AEs (SAEs) reported. The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (5.6%) and application site dryness (2.8%). Local cutaneous safety and tolerability assessments were generally mild to moderate and improved by Week 12. Slight increases in mean scores were observed for scaling, burning, and stinging within the first four weeks of treatment, and appeared to be transient. A limitation of the study is that it was a post-hoc analysis.

Conclusion: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in preadolescent acne. The new lotion formulation was well-tolerated, and all treatment-related AEs were both mild and transient in nature.

Funding/Disclosures: LFE and JLS are advisors to Ortho Dermatologics and investigators with Dow Pharmaceutical Sciences. EG and VB are employees of Bausch Health.

Safety and efficacy of clascoterone (cortexolone 17alpha propionate, CB-03-01) 1% cream for the treatment of acne vulgaris: summary of early phase study results

Presenters: Mazzetti A, Moro L, Gerloni M, Cartwright M

Affiliations: Cassiopea SpA, Milan, Italy

Background/Objective: Two Phase III investigations of clascoterone cream 1% for the treatment of moderate-to-severe acne vulgaris in individuals nine years of age or older recently concluded. The cream’s active ingredient is clascoterone, for which safety and efficacy are supported by 26 nonclinical, five Phase I, and three Phase II studies. Approximately 770 subjects have been exposed to clascoterone creams. Here, we summarize the key results of the studies that led to the Phase III trials.

Methods: Clascoterone cream 1% for acne vulgaris investigations included Phase I, single-dose pharmacokinetics (PK) study in 24 healthy volunteers; a randomized, double-blind, vehicle-controlled, single-ascending dose Phase I repeat dose PK study in 24 healthy volunteers; a Phase I, steady-state PK study in eight subjects with acne vulgaris, which was single center, open-label, pilot, six-week repeat-dose; a Phase I, three-week cumulative skin irritation study in 36 healthy volunteers; a Phase I repeat insult patch test with 1% clascoterone cream in 202 healthy subjects; a Phase II hypothalamic-pituitary-adrenal (HPA)/PK study in 42 subjects with acne vulgaris; an open-label, 14-day, repeat-dose, Phase II, proof-of-concept study in 72 adult subjects with facial acne vulgaris; a randomized, double-blind, vehicle-controlled, active-comparator, tretinoin 0.05% cream, eight-week, repeat-dose, Phase II, dose-escalating study in 363 subjects with facial acne vulgaris; a multicenter, randomized, double-blind, vehicle-controlled, 12-week repeat-dose evaluation of clascoterone cream (0.1% twice/day, 0.5% twice/day, 1% daily, or 1% twice/day) versus vehicle with about 90 subjects per cohort over 12 weeks in subjects with facial acne vulgaris.

Results: The four Phase I studies (N=92) affirmed that topical application of the 1% cream is well tolerated, with no measurable systemic side effects. The active ingredient permeates the skin to the dermal levels, with cortexolone 17alpha-propionate and metabolites quantifiable at low plasma levels. The three Phase II studies (N=477) revealed minimal systemic absorption; the active ingredient works locally within hair follicle. Subjects did not show clinical evidence of adrenal suppression under maximal use conditions. Local side effects were mostly mild. The 1% cream twice per day was determined to be the ideal concentration and delivery; therefore, it was selected for the subsequent Phase III clinical trials.

Conclusion: Clascoterone cream 1% is well tolerated locally, results in minimal systemic exposure when applied topically, and has a clinical safety profile similar to the vehicle. The 1% concentration, applied twice daily, is significantly more effective than the vehicle at reducing inflammatory and noninflammatory lesions in adolescents and adults.

AESTHETICS

Diluted and hyperdiluted calcium hydroxylapatite (Radiesse®) for skin tightening: guidelines from a global consensus panel

Presenters: Goldie K¹, Peeters W², Alghoul M³, Butterwick K⁴, Casabona G⁵, Chao YYY⁶, Costa J⁷, Eviatar J⁸, Fabi SG⁹, Lupo M¹⁰, Sattler G¹¹, Waldorf H¹², Yutskovskaya Y¹³, Lorenc P¹⁴

Affiliations: ¹Medical Director and Founder, European Medical Aesthetics Ltd, London, UK; ²Head of Plastic & Reconstructive Surgery, AZ KLINA Brasschaat, Belgium; ³Assistant Professor, Division of Plastic & Reconstructive Surgery, Northwestern Feinberg School of Medicine, Chicago, IL; ⁴Cosmetic Laser Dermatology, San Diego, CA; ⁵Medical Director, Beauty Beyond Skin Clinic, Sao Paulo, Brazil; ⁶CHAO Institute of Aesthetic Medicine, Taipei, Taiwan; ⁷Dermatologist, Brasília, Brazil; ⁸Director of Aesthetic Medicine, OMNI Aesthetic MD, Assistant Clinical Professor, State University of New York, College of Optometry, New York City, NY; ⁹Cosmetic Laser Dermatology, Volunteer Assistant Clinical Professor, University of California San Diego, CA; ¹⁰Clinical Professor of Dermatology, Tulane Medical school, New Orleans, LA; ¹¹Rosenparkklinik, Darmstadt, Germany; ¹²Waldorf Dermatology Aesthetics, Nanuet, New York and Department of Dermatology, Mount Sinai Hospital, New York, NY; ¹³Dermatologist, Pacific State Medical University of Health, Moscow, Russia; ¹⁴Plastic Surgeon, New York, NY

Background/Objective: Calcium hydroxylapatite (CaHA, Radiesse®, Merz North America) is approved to correct moderate-to-severe wrinkles and folds and soft-tissue volume loss in the face and hands. More recently, subdermal injection using diluted Radiesse has been used to improve skin laxity. Consensus-based guidelines were developed for the usage of diluted and hyperdiluted Radiesse for treating skin laxity and superficial wrinkles. The intent is to provide clear preliminary guidelines for the novel, off-label use of diluted Radiesse as a biostimulatory agent in the face and body, with a focus on properties of diluted or hyperdiluted Radiesse that stimulate neocollagenesis and lead to skin tightening and improvement of skin quality (defined as elasticity, firmness, roughness, superficial wrinkles, and appearance). Highly diluted Radiesse treatment has been reported to reduce skin laxity, in part due to the collagen stimulating effects of CaHA. Some practitioners might dilute initially with lidocaine to reduce discomfort, then add normal saline solution to achieve further dilution. Dilution can expand use of Radiesse to treat areas of the body other than the face that require more product spread, although this technique is not approved for this purpose and is considered off-label. Multiple studies have reported the effectiveness of Radiesse mixed with varying amounts of diluent to tighten the skin and improve the appearance of the neck, décolletage, upper arms, abdomen, buttocks, thighs, breasts, and knees.

Methods: A global panel of 14 expert aesthetic physicians developed consensus-based guidelines and best-practice recommendations for treating laxity and superficial wrinkles in multiple areas of the face and body using diluted (1:1) and hyperdiluted (greater than or equal to 1:2) Radiesse. The experts documented their clinical experience and provided recommendations for safe and effective use of subdermal injection of diluted and hyperdiluted Radiesse to stimulate targeted neocollagenesis to improve laxity and skin quality in the mid and lower face, neck and décolletage, upper arms, buttocks, thighs, and abdomen. A questionnaire served as a basis for the discussions; an agreement of more than 75 percent of panel members constituted consensus.

Results: To treat mild dermal irregularities in the buttocks, 1.5mL Radiesse was diluted with 3mL of lidocaine and saline (1:2 ratio); 2mL was injected per side in the deep dermis. Skin tightening was accomplished by layering 1.5mL Radiesse diluted with 9mL of lidocaine and saline (1:5 ratio) using a crosshatching technique; 6mL of solution was injected per side. Baseline appearance of striae was much improved after treatment with 1:1 diluted Radiesse followed by three sessions of topical ascorbic acid and microneedling one month after the last treatment session.

Conclusion: Radiesse has been used safely and effectively for over a decade to correct moderate-to-severe wrinkles and folds and soft-tissue volume loss. When injected more superficially in the subdermal plane in its diluted and hyperdiluted form, Radiesse appears to promote dermal remodeling through stimulation of collagen and elastin to create a skin-tightening effect and improve superficial wrinkles, elasticity, and skin thickness. With limited evidence in the current literature, this report provides preliminary guidelines for the novel use of Radiesse as a biostimulatory agent in the face and body.

Funding/Disclosures: This study was sponsored by Merz North America, Inc.

Efficacy, safety, and durability of collagenase clostridium histolyticum for the treatment of edematous fibrosclerotic panniculopathy (cellulite)

Presenters: Kaufman J¹, Bass LS², Xiang Q³, McLane MP³, Kirby MT³

Affiliations: ¹Skin Associates of South Florida, Coral Gables, FL; ²Bass Plastic Surgery PLLC, New York, NY; ³Endo Pharmaceuticals Inc., Malvern, PA

Background/Objective: Cellulite is a contour abnormality of the skin that affects most postpubertal women and is associated with a dimpled appearance. Although the pathophysiology of cellulite has not been fully elucidated, the combination of subcutaneous adipose protrusion and orientation and thickening of collagen-rich septae appears to play a role in the altered skin topography. Collagenase clostridium histolyticum (CCH) for injection is currently indicated in the United States for the treatment of collagen-associated disorders (e.g., adults with Dupuytren’s contracture with a palpable cord or Peyronie’s disease in adult men with a palpable plaque and penile curvature deformity greater than or equal to 30° at start of therapy). A novel presentation of CCH is being investigated as a treatment to correct cellulite-related contour alterations in women, with the mechanism of action being enzymatic disruption of the septae, which creates a skin-smoothing effect. In one Phase II (N=375) and two Phase III (N=423 and N=422), randomized, double-blind, placebo-controlled studies that enrolled women with moderate-to-severe cellulite on the buttocks or posterolateral thighs (Phase II) or the buttocks (Phase III), subcutaneous CCH significantly improved the appearance of cellulite versus placebo based on both clinician and patient ratings and was generally well tolerated. Our aim was to evaluate the durability of response and safety of CCH for the treatment of cellulite in women.

Methods: This was an open-label extension (OLE) trial (Study 202; clinicaltrials.gov identifier: NCT02942160) of the Phase II, randomized, double-blind, placebo-controlled trial (RCT; Study 201). The original double-blind RCT included women with moderate-to-severe cellulite (Clinician Reported Photonumeric Cellulite Severity Scale [CR-PCSS] and Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] scores of 3–4 and Hexsel Cellulite Severity Scale score less than or equal to 13) of the buttocks or posterolateral thighs received up to three sets of injections (Days 1, 22, and 43) of subcutaneous CCH 0.84mg (3.6mL total volume) or placebo. Women who completed the double-blind RCT could enroll in the OLE trial and be under observation only or receive CCH treatment. After double-blind RCT unblinding, women with moderate-to-severe cellulite were eligible for open-label CCH treatment (buttocks or posterolateral thighs) following the same CCH treatment regimen as the double-blind RCT, either in the same area or a different area than in the double-blind RCT (CCH Treatment Course 1); iInitial CCH treatment in women previously treated with placebo in double-blind RCT (CCH Treatment Course 1); retreatment with CCH in the same or different area from CCH Treatment Course 1 in eligible women (CCH Treatment Course 2). For women enrolled in the observation group (no additional CCH treatment), efficacy assessments were conducted starting 90±7 days after Day 1 of the double-blind RCT (Days 90, 180, 270, and 360).

Results: In total, 259 women were enrolled in the observation phase. Nineteen of the enrolled women responded to the double-blind RCT with a greater-than-two-level improvement from RCT baseline in both CR-PCSS and PR-PCSS at Day 71, 16 of whom had assessments at 360 days. Fifty-three of the enrolled women responded to the double-blind RCT with a greater-than-one-level improvement from RCT baseline in both CR-PCSS and PR-PCSS at Day 71, 45 of whom had assessments at 360 days. Response to CCH treatment was durable for at least 360 days. All (100%) evaluable two-or-greater-level composite responders had durable response at 180 days and 360 days after initial dosing in the double-blind RCT. Also, 94.3 percent and 95.6 percent of evaluable one-or-greater-level composite responders had a durable response at 180 days and 360 days, respectively, after initial dosing in the double-blind RCT. The most common treatment-emergent AEs were injection-site bruising and injection-site pain. Most AEs were mild to moderate in intensity and few (3.0%) women discontinued from the study due to an AE. Overall, 163 women received two CCH treatment courses, and the AE profile by CCH treatment course was assessed; the AE profiles were generally similar during both CCH treatment courses. The AE profiles were consistent with the AE profile of the overall safety population.

Conclusion: CCH treatment provided durable improvement in cellulite appearance. CCH was generally well tolerated. The AE profile during a second CCH treatment course was generally similar to that observed in the same population after the first CCH treatment course and the overall population of patients treated with CCH.

Funding/Disclosures: JK reports serving as a clinical investigator and consultant for Endo Pharmaceuticals Inc. LSB reports being an advisory board participant for Endo Pharmaceuticals Inc. and Merz North America, being a clinical investigator for Endo Pharmaceuticals Inc., and serving as a consultant for Viveve. QX and MPM are employees of Endo Pharmaceuticals Inc. MTK is a former employee of Endo Pharmaceuticals Inc.

Escalating doses of incobotulinumtoxinA for extended treatment of glabellar frown lines: safety and efficacy results from a randomized, double-blind study

Presenters: Maas C

Affiliations: The Maas Clinic

Background/Objective: The effect of escalating doses of incobotulinumtoxinA (>20U for glabellar frown lines [GFL]) on response rates and duration of response has not been studied. Previously, analysis of a pilot study suggested a roughly linear relationship to duration of response with doses escalating in 20U increments. In this study, the effect of varying doses of incobotulinumtoxinA on the safety, efficacy, and duration of treatment effect for GFL was assessed.

Methods: Subjects (N=37) with moderate-to-severe GFL (Merz Aesthetics Scales [MAS]) were randomized to receive 1 of 3 doses: 20U (control; n=8), 60U (n=11), and 100U (n=17). The mean time to return to baseline for mean MAS scores (at maximum frown) was used to assess duration of response. Subjects with a two-or-greater-point improvement in wrinkle severity at maximum contraction were also assessed over time.

Results: A strong dose response was observed for clinical efficacy and duration of effect. An increase in the duration of effect was noted with higher doses; mean scores returned to baseline at about four months (20U), about seven months (60U), or 11 months or more (100U). Treatment response was highest in the 60U and 100U dose groups; by nine months, 23 percent of those in the 100U group remained responders. Overall subject satisfaction was high. All AEs (19 total in 14 subjects) were consistent with previous incobotulinumtoxinA studies, and none were considered related to distant spread of toxin. A somewhat higher incidence of AEs was noted in the 100U dose group (47% of subjects) compared to other groups (25–36% of subjects).

Conclusion: Within the range of doses examined, there was a roughly linear relationship between incobotulinumtoxinA dose and duration of treatment effect. Safety of incobotulinumtoxinA at higher doses was favorable, with no unexpected safety findings. Overall, findings suggest that the dose of incobotulinumtoxinA for GFL might be safely increased from the standard 20U to help achieve treatment goals of patients, including duration of effect.

Funding/Disclosures: CM has served as consultant and investigator for Merz North America, Inc. This study was sponsored by a grant from Merz North America, Inc.

A multicenter, open-label, prospective study of cannula injection of large-gel particle hyaluronic acid with lidocaine for cheek augmentation and the correction of age related midface contour deficiencies

Presenter: Jones DH¹, Hessler J², Chapas A³, Jonas B⁴, Chopra R⁵

Affiliation: ¹Skin Care and Laser Physicians of Beverly Hills, Los Angeles, CA; ²Hessler Plastic Surgery, Palo Alto, CA; ³Union Square Laser Dermatology, New York, NY; ⁴Galderma R&D, LCC, Fort Worth, TX; ⁵Facial Plastic & Cosmetic Surgery Medical Corp, Beverly Hills, CA

Background/Objective: The purpose was to evaluate the safety of large-gel particle hyaluronic acid with lidocaine (HAL) administered with a small, blunt-tip cannula for cheek augmentation and correction of age-related midface contour deficiencies.

Methods: This was a 16-week, prospective, multicenter, open-label, single-arm study. Subjects (N=60) aged 22 years or older with mild-to-substantial loss of fullness in the midface area (Score 2–4 on Medicis Midface Volume Scale [MMVS]) were included. HAL was injected into the midface using a small, blunt-tip cannula to optimal augmentation. At Week 16, retreatment was performed if needed. The primary objective of the study was to evaluate safety, including occurrence of adverse events (AEs), predefined symptoms by subject diary, and evaluation of midface function. Secondary objectives included Global Aesthetic Improvement Scale (GAIS) assessments by subjects and investigators, MMVS assessments by investigators, and subject satisfaction.

Results: The mean injection volume (right and left midface combined) at the initial treatment was 3.0mL (n=60) and 1.6mL (n=43) at the optional retreatment. Of the five AEs reported during the study, only one AE (mild presyncope) was assessed as related to the device and/or injection procedure. The majority of subjects (98%) reported at least one predefined diary symptom. Tenderness was most commonly reported (92%), followed by swelling. The majority were tolerable and resolved within seven days. The majority of both subjects and investigators reported improvement from baseline at all timepoints (91.5–100%) using GAIS. The MMVS responder rate (1-point-or-greater improvement) for right and left midface combined was never below 83 percent. There was a high level of subject satisfaction with treatment.

Conclusion: Midface treatment with HAL using a small blunt-tip cannula was well-tolerated for cheek augmentation and correction of age related midface contour deficiencies and provided visible aesthetic improvement.

Funding/Disclosures: Research funded by Galderma R&D, LLC. DHJ and JH are paid clinical trial investigators for Galderma. AC received a research grant from Galderma R&D, LLC and is a paid clinical trial investigator for Galderma. BJ is an employee of Galderma, R&D, LLC. RC is a paid advisor, speaker, and clinical trial investigator for Galderma. Dr. Hicks is an employee of Galderma Laboratories, L.P.

Multicenter pivotal study of the safety and effectiveness of Cellfina® for the treatment of cellulite—five-year update

Presenter: Kaminer MS¹, Coleman WP III², Weiss RA³, Robinson DM⁴, Grossman J⁵

Affiliation: ¹SkinCare Physicians, Chestnut Hill, MA; ²Coleman Center for Cosmetic and Dermatologic Surgery, Metairie, LA; ³Maryland Laser Skin and Vein Institute, Hunt Valley, MD; ⁴Connecticut Dermatology Group, Milford, CT; ⁵Merz North America, Raleigh, NC

Background/Objective: The appearance of cellulite has been associated with significant social stigma and adverse effects on self-esteem and quality of life. Overall, 85 percent of women have cellulite, yet many do not consider it a medical condition that requires treatment from a physician. Cellfina (Merz North America, Raleigh, NC) provides controlled subcision for precise and reproducible release of cellulite dimples. This unique, patented technology with tissue capture allows for dimple release at precise depths by treating tethered fibrous septae bands, the structural cause of cellulite dimples.

Methods: The primary endpoint was a mean of one-or-greater-point reduction on the six-point Cellulite Severity Scale (0–5), determined by independent physician assessment (IPA) of subject photographs taken before and five years after treatment. One secondary endpoint was the improvement in severity by one or more grades (none, mild, moderate, severe) in more than 60 percent of treated subjects, determined by IPA of subject photographs taken before and five years after treatment. Another secondary endpoint was the improvement in cellulite appearance by IPA using GAIS (Global aesthetic Improvement Scale), percent correct selection of before/after treatment photos by IPA, subject satisfaction, and subject pain ratings. Safety endpoints were serious adverse events (SAEs) directly attributable to the Cellfina System or procedure.

Results: The average improvement on the Cellulite Severity Grade, on a scale of 1 to 5, peaked at 2.1 points after three months and was 1.8 points by Year 5. Additionally, by Year 5, 87 percent of patients reported at least a one-point improvement in the Cellulite Severity Grade, and 100 percent of subjects had noticeable GAIS improvement. Furthermore, 59.4 percent indicated that the cellulite “improved,” 29.7 percent indicated “much improved,” and 5.4 percent indicated “very much improved” based on GAIS scores after five years. Among the 37 patients who reached Year 5, 78 percent said they were satisfied with the treatment.

Conclusion: The results of this Cellfina study demonstrate that improvement in the appearance of cellulite on the buttocks and thighs are maintained at least five years after a single, in-office Cellfina procedure with minimal adverse effects. The Cellfina system treats the structural cause of cellulite and provides the longest result duration of any United States Food and Drug Administration (FDA)-cleared cellulite treatment.

Funding/Disclosures: The study was sponsored by Merz North America, Inc. JG is a former employee of Merz North America.

Multicenter pivotal study of the safety and effectiveness of a tissue-stabilized, guided subcision procedure for the treatment of cellulite—five year update

Presenters: Kaminer MS¹, Coleman WP III², Weiss RA³, Robinson DM⁴, Coleman WP IV²

Affiliations: ¹SkinCare Physicians, Chestnut Hill, MA; ²Coleman Center for Cosmetic and Dermatologic Surgery, Metairie, LA; ³Maryland Laser Skin and Vein Institute, Hunt Valley, MD; ⁴Connecticut Dermatology Group, Milford, CT

Background/Objective: Tissue release (subcision) for cellulite has been practiced for decades with limited success. A novel procedure has been developed that stretches and stabilizes tissue while providing integrated anesthesia delivery and precise depth control of minimally invasive tissue release. The pivotal study supported the United States Food and Drug Administration (FDA)-clearance of this novel tissue stabilized-guided subcision (TS-GS) system as an effective and safe treatment for the long-term improvement in the appearance of cellulite in the buttocks and thighs with no diminishment of benefit for up to three years. The purpose of this study update was to determine the safety and efficacy of TS-GS for maintained improvement in the appearance of cellulite of the buttocks and thighs for up to five years.

Methods: A pivotal, prospective, multicenter safety and effectiveness study enrolled 55 subjects. Subjects underwent a single treatment and were followed at regular intervals for five years. Safety was assessed and effectiveness was evaluated by blinded, independent physician evaluators using randomized (before and after) professional photographs and the novel, validated, six-point (0–5) Cellulite Severity Scale.

Results: Treatments were well tolerated, with minor expected side effects that resolved quickly. Improvement was rapid and pronounced. Thirty-seven subjects completed five-year follow-ups. Five-year average reduction in cellulite severity was 1.8 points (p<0.0001), and masked evaluator improvement was 92.8 percent. At five years, evaluators rated 100 percent of subjects as having noticeable improvement, and 78.4 percent of subjects were either satisfied or very satisfied.

Conclusion: Tissue release at precise depths leads to significant improvements in cellulite lasting up to five years. The results of this study demonstrate that a single treatment with a novel TS-GS release system improved the appearance of cellulite on the thighs and buttocks through five years of follow-up with minimal adverse effects.

Funding/Disclosures: All authors have been consultants and/or investigators for Merz North America, Inc. This study was sponsored by Merz North America, Inc.

Optimizing patient outcomes through a customized approach of microfocused ultrasound with visualization treatments: consensus guidelines

Presenters: Fabi S

Affiliations: Cosmetic Laser Dermatology, San Diego, CA

Background/Objective: Microfocused ultrasound with visualization (MFU-V) is approved by the United States Food and Drug Administration (FDA) for lifting the skin of the brow, neck, and submentum, as well as for improvement of lines and wrinkles of the décolleté. The aim of these consensus guidelines is to provide a framework for a customized treatment plan informed by key patient characteristics and proper use of MFU-V to assess skin anatomical features.

Methods: Consensus guidelines were developed by a global panel of expert aesthetic physicians for the use of MFU-V. Key discussion topics included patient factors that contribute to favorable or poor outcomes; customization of the number of treatment lines, energy settings, and treatment depths; distinguishing approaches for restorative, preventative, and maintenance treatments; and important safety considerations.

Results: Use of MFU-V is the most important factor for selecting transducers/treatment depth and planning the number of lines at each depth. Higher density treatments are associated with ideal outcomes. Treatment intervals should be tailored to age, with older patients requiring more frequent treatments to maintain results driven by continued collagen production. Because neocollagenesis is valuable to all patients, MFU-V can be applied for both preventative and restorative treatments. In addition to proper technique, the most important factors associated with positive outcomes are management of patient expectations and proper diagnosis.

Conclusion: Supported by a large body of literature, a well-characterized mechanism of action, and high reported patient satisfaction, MFU-V is considered by the panel to be a key aesthetic treatment and the gold standard for nonsurgical lifting and tightening of the skin. These guidelines expand upon available evidence and clinical data to provide a framework for physicians to fully customize their approach with MFU-V, leading to favorable outcomes that are integral to a patient’s overall aesthetic treatment plan.

Funding/Disclosures: SF has been a consultant and investigator for Merz North America, Inc. This study was sponsored by Merz North America, Inc.

A prospective, multicenter, randomized, evaluator-blinded, split-hand study to evaluate the effectiveness and safety of large-gel particle hyaluronic acid with lidocaine for the correction of volume deficits in the dorsal hand

Presenters: Moradi A¹, Allen S², Bank D³, Marmu E⁴, Fagien S⁵, Glaser DA⁶, Maguire C⁷, Cohen J⁸, Arlati L⁹

Affiliations: ¹Moradi MD, Vista, CA; ²Dermatology Specialists, Boulder, CO; ³The Center for Dermatology, Cosmetic, & Laser Surgery, Mt Kisco, NY; ⁴Marmur Medical, New York, NY; ⁵Private Practice, Boca Raton, FL; ⁶Saint Louis University, Dermatology, St. Louis, MO; ⁷Galderma R&D, LLC, Fort Worth, TX; ⁸Director of AboutSkin Dermatology and DermSurgery, Greenwood Village and Lone Tree, CO; Associate Clinical Professor, Department of Dermatology, University of Colorado, Boulder, CO; Assistant Clinical Professor, Department of Dermatology, University of California Irvine, Irvine, CA; ⁹Galderma Laboratories, L.P., Fort Worth, TX

Background/Objective: There are currently only a few treatments approved for the correction of volume loss in the hand. Increased popularity of hand rejuvenation has brought a need for published data on the use of hyaluronic acid (HA) gels for this indication. Large-gel particle hyaluronic acid with lidocaine (HAL; Restylane® Lyft with Lidocaine [Q-Med AB/Galderma, Uppsala, Sweden]) is a HA gel, approved by the United States Food and Drug Administration (FDA) for treatment of moderate-to-severe facial folds, wrinkles, and cheek augmentation. The primary objectives of this study (ID ClinicalTrials.gov NCT02650921) were to demonstrate superiority of HAL, relative to no treatment, for the correction of volume deficit in the dorsal hand, and to define the incidence of adverse events (AEs) and subject diary reported injection site reactions.

Methods: A prospective, multicenter, randomized, evaluator-blinded, split-hand study was conducted. Male and female subjects in the United States (n=89 safety population; n=85 intent-to-treat [ITT] population), aged 22 years or older, with a volume deficit in the dorsal hand (Merz Hand Grading Scale [MHGS] score of 2 [Moderate] to 4 [Very Severe]) were randomized to treatment with HAL in either the right or left hand. Agreement on MHGS assessed by blinded evaluator and treating investigator upon live assessment was not required, and MHGS scores between hands were not required to match. Initial treatment was administered in one hand at baseline (Day 0; n=89), with an optional touch-up at Week 4 (n=74) if optimal treatment results were not met and both investigator and subject agreed it would be beneficial. At Week 24 (Month 6; n=70), an optional retreatment was performed (no touch-up). The untreated control hand received optional treatment at Week 24 (n=77), with optional touch-up after four weeks (n=44). For a vast majority of subjects who did not receive optional touch-ups and retreatment, optimal results had been obtained. HAL was applied subcutaneously using either a 29G×½-inch, thin-walled needle or 25G×1½-inch, blunt-tip cannula (5 needle sites; 2 cannula sites). However, this presentation only included needle data because the study was not designed or powered to assess the safety and effectiveness of the use of cannula or compare its performance with the use of a needle.

Results: The primary efficacy objective of demonstrating superiority with treatment was met, with a statistically significant higher percentage of responders (i.e., hand with at least a 1-grade improvement from baseline on the MHGS by blinded evaluation), in the treated hand at Week 12. Responder rates remained high (>75%) throughout Week 24. Central Independent Photographic Reviewer (CIPR) assessments showed improvements in the treated hands compared with the untreated hand from Week 12 to Week 24 (range 69.5–88.1%). Also, the blinded photo evaluators were consistently able to differentiate the treated hand from the untreated hand up to Week 24. Most subjects and investigators (92.8% or greater) reported improvement on the Global Aesthetic Improvement Scale (GAIS) compared to baseline at all time points. A majority of subjects were happy with the overall treatment and felt their treated hands appeared more attractive and youthful. Most subjects would recommend the treatment to a friend (84.5%) and would do the treatment again (77.4%).

Conclusion: The study demonstrated an aesthetic improvement of the hands after HAL treatment with a sharp needle that was stable over the course of the study (up to 6 months). Treatment was safe and well tolerated and superior to no treatment for the correction of volume deficits in the dorsal hand. These results support the clinical utility of HAL for restoring volume loss in the hand.

Funding/Disclosures: Research funded by Galderma R&D, LLC; poster/editorial support provided Galderma Laboratories, L.P.

Understanding the Hispanic/Latino facial aesthetic patient

Presenters: Aguilera SB¹, Vivian Bucay V², Fabi S³, Montes JR⁴, Manson S⁵, Shumate GT⁵, Gallagher CJ⁵

Affiliations: ¹SHINO BAY Cosmetic Dermatology & Laser Institute, Fort Lauderdale, FL; ²Bucay Center for Dermatology and Aesthetics, San Antonio, TX; ³Cosmetic Laser Dermatology, San Diego, CA; ⁴José Raúl Montes Eyes & Facial Rejuvenation, San Juan, Puerto Rico; ⁵Allergan plc, Irvine, CA

Background/Objective: Hispanic and Latino people comprise the largest ethnic minority group in the United States, projected to reach 119 million people (28.6% of total population) by 2060. In 2016, cosmetic procedures were performed more commonly in this minority group than in others. From 2006 to 2016, the total number of United States cosmetic procedures that Hispanic and Latino subjects received increased by 77 percent. The distinct facial aging patterns, anatomical considerations, aesthetic concerns, and treatment preferences of Hispanic and Latino individuals might require a unique approach to facial aesthetic treatment. The objective of this study was to combine research findings and practical case studies to increase the comfort level of aesthetic injectors serving the Hispanic/Latino patient population and improve outcomes for patients.

Methods: Study 1 was an international study that included 3,267 female respondents aged 18 to 75 (mean 47±16) years in the United States, Canada, United Kingdom, and Australia, with a subpopulation of 526 Hispanic/Latino women. The respondents rated their signs of facial aging using validated photonumeric scales (from none to severe/extreme) with reference to 4 to 6 photographs depicting ascending degrees of severity for each of 10 static facial features, including the upper face (forehead, glabellar, and crow’s feet lines), midface (puffiness under the eye, tear troughs, and midface volume loss), and lower face (nasolabial folds, oral commissures, perioral lines, and lip volume loss). Study 2 was a United States-based study and included 1,205 female participants, aged 30 to 65 years (mean 48±16), 401 of whom were Hispanic/Latino. Inclusion criteria required that respondents have at least some discretionary income and be aesthetically oriented. Respondents viewed a diagram of a female face with marked areas defined in a corresponding table and reported their most bothersome facial areas using a six-point Likert scale (1=not at all bothered; 6=very bothered). Respondents also reviewed these same facial areas, listed in different (numerical) orders, and ranked them as most likely or least likely to be prioritized in a future treatment using maximum difference (MaxDiff) question format and analysis, for which outputs included an average ranking of importance (“average performance value”) for all areas combined and areas most/least likely to be prioritized for treatment as determined by the MaxDiff scaling system.

Results: Hispanic/Latino respondents were diverse in ethnic/racial heritage and Fitzpatrick skin phototype. At least 30 percent of Hispanic/Latino female respondents in Study 1 (n=526) reported moderate or severe nasolabial folds being present in their 40s. Upper facial lines (crow’s feet lines, forehead lines, and glabellar lines) and midface volume loss reached the moderate-to-severe threshold for Hispanic/Latino respondents 10 years later compared with data obtained for 1,317 Caucasian women. Hispanic/Latino women were more bothered by their facial areas compared to data obtained for Asian and African American respondents. Hispanic/Latino women were most bothered by sagging underneath the chin/double chin, the periorbital area (under eye/tear trough and crow’s feet lines), and forehead lines. Correspondingly, areas most likely to be prioritized for treatment first included under eye/tear trough and crow’s feet lines, followed by sagging underneath the chin/double chin and forehead lines. The areas least likely to be prioritized for treatment included the temple and the lips. The majority of Hispanic/Latino respondents reported having facial wrinkles (56%), dark circles under the eyes (55%), and bags under the eyes (45%). Compared to results for a predominantly Caucasian female population, Hispanic/Latino women were less likely to prioritize treatment of oral commissures and glabellar lines and more likely to prioritize treatment of tear troughs. Age-dependent analysis of the most bothersome signs of facial aging and areas most likely to be prioritized for treatment revealed that treating tear troughs and crow’s feet lines was more important to younger Hispanic/Latino women (aged 30–44) than older women (aged 45–65). A greater proportion of Hispanic/Latino women (85%) reported considering facial injectable treatments than Asian women (74%) or African American women (64%). Cost, safety or side effects, and concerns about receiving an injection of a foreign substance were the most commonly reported barriers to receiving injectables. Hispanic/Latino respondents did not report higher incomes than Asian or African American respondents, yet their monthly and one-time spending on aesthetic products/services was the greatest.

Conclusion: There was general alignment between the self-reported facial aging patterns, areas of greatest aesthetic concern, and facial areas that were prioritized for treatment. The periorbital area (crow’s feet lines and under eye/tear trough), forehead lines, and submental region might be seen as entry points for initiating treatments with injectables in this population. Hispanic/Latino respondents reported spending more on aesthetic products and services than Asian and African American respondents. In addition, a higher percentage of Hispanic/Latino respondents (85%) would consider injectables compared to Asian and African American respondents. An understanding of these research study findings and practical case studies might increase the comfort level for injectors and improve outcomes for the Hispanic/Latino patient population.

Funding/Disclosures: This study was sponsored by Allergan plc, Dublin, Ireland. Writing and editorial assistance was provided to the authors by Erika Von Grote, PhD, of Allergan plc. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. SBA serves as a speaker and trainer for Allergan plc, Cynosure, Galderma, and Merz Aesthetics. VB serves as a speaker and consultant for Allergan plc, Galderma, and Merz Aesthetics. SF serves as a consultant, researcher, or advisory board member for Allergan, Galderma, Merz Aesthetics, and Revance. RM serves as a speaker and trainer for Allergan plc, Galderma, and Merz Aesthetics. GTS is an employee of Allergan plc and may own stock/options in the company. CJG was an employee of Allergan plc at the time this study was conducted. Data from this study was previously presented at the Cosmetic Bootcamp (CBC), June 21, 2018, Aspen, CO.

ATOPIC DERMATITIS

Dupilumab efficacy and safety in adolescents with moderate-to-severe atopic dermatitis: results from a multicenter, randomized, placebo-controlled, double-blind, parallel-group, Phase III study

Presenters: Simpson EL¹, Paller AS², Siegfried EC³, Boguniewicz M⁴, Pariser DM⁵, Blauvelt A⁶, Hultsch T⁷, Staudinger H⁸, Zhang R⁹, Kamal MA¹⁰, Davis JD¹⁰, Graham NMH¹⁰, Bansal A¹⁰

Affiliations: ¹Oregon Health & Science University, Portland, OR; ²Northwestern University Feinberg School of Medicine, Chicago, IL; ³Saint Louis University and Cardinal Glennon Children’s Hospital, St. Louis, MO; ⁴National Jewish Health and University of Colorado School of Medicine, Denver, CO; ⁵Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; ⁶Oregon Medical Research Center, Portland, OR; ⁷Sanofi Genzyme, Cambridge, MA; ⁸Sanofi, Bridgewater, NJ; ⁹Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ; ¹⁰Regeneron Pharmaceuticals, Inc., Tarrytown, NY

Background/Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with atopic comorbidities. Limited treatment options are available for adolescents. No systemic agent currently provides a favorable long-term benefit:risk profile for pediatric patients with AD inadequately controlled by topical therapies. Dupilumab is a fully human, VelocImmune®-derived monoclonal antibody directed against the interleukin (IL)-4R-alpha subunit of the IL-4 and IL-13 receptors. IL-4 and IL-13 are Type 2 cytokines that mediate many features of AD. Dupilumab is approved for subcutaneous administration at 300mg every two weeks (Q2W) for the treatment of adults with moderate-to-severe AD that is inadequately controlled with topical prescription therapies or when those therapies are not advisable, and for use in adults with inadequately controlled moderate-to-severe AD who are candidates for systemic therapy. The objective of the study was to evaluate the efficacy and safety of dupilumab monotherapy versus placebo in adolescents with moderate-to-severe AD inadequately controlled by topical therapies.

Methods: This was a randomized, placebo-controlled, double-blind, parallel-group Phase III trial of dupilumab in adolescents with moderate-to-severe AD (NCT03054428). Patients were randomized (1:1:1) to 16-week treatment with 200/300mg dupilumab Q2W, 300mg dupilumab every four weeks (Q4W), or placebo. The co-primary endpoints were proportion of patients with an Investigator Global Assessment (IGA) score of 0 or 1 at Week 16 and proportion of patients with a 75-percent-or-greater reduction in Eczema Area and Severity Index (EASI) scores (EASI-75) at Week 16. Continuous secondary endpoints were analyzed using multiple imputation with analysis of covariance ([ANOVA] data from patients with rescue medication were considered “missing” first, then imputed by multiple imputation). Pharmacokinetics were analyzed in all randomized patients who received any study drug and who had one or more nonmissing drug concentration result following the first dose of study drug. Safety was analyzed among all randomized patients who received at least one injection of the study drug.

Results: In total, 251 patients were randomized to dupilumab Q2W (n=82; 43 received 200mg, 39 received 300mg), dupilumab Q4W (n=84), or placebo (n=85). One patient in the dupilumab Q4W group was randomized but did not receive study treatment. Compared to placebo, significantly more dupilumab-treated patients achieved IGA 0/1 and EASI-75 at Week 16 in a censored analysis (primary analysis, patients who received rescue medication were considered as nonresponders, p<0.001 for all comparisons vs. placebo); similarly to the censored analysis, significantly more dupilumab versus placebo patients achieved IGA 0/1 and EASI-75 at Week 16 in an analysis considering all patients, regardless of rescue treatment use. Dupilumab also significantly improved Week 16 patient itch and Week 16 EASI scores compared to placebo (p<0.001 for all comparisons). Furthermore, a significantly higher proportion of patients receiving any dupilumab regimen compared to placebo achieved at least a three- or four-point improvement in their peak weekly pruritus Numerical Rating Scale (NRS) scores, EASI-50 and EASI-90 at Week 16, and percent-change in SCORing Atopic Dermatitis (SCORAD) from baseline to Week 16 (p<0.001 for all comparisons). All dupilumab regimens compared with placebo significantly improved measures of quality of life assessed as change from baseline to Week 16 in Children’s Dermatology Life Quality Index (CDLQI) and Patient Oriented Eczema Measure (POEM, p<0.001, for all comparisons) and numerically improved Hospital Anxiety and Depression Scale (HADS) scores. Finally, a numerically higher proportion of patients used rescue medications in the placebo versus dupilumab groups and in the Q4W versus Q2W dupilumab group.

Conclusion: In adolescents with moderate-to-severe AD, dupilumab treatment resulted in clinically meaningful and statistically significant improvements in AD signs and symptoms (including pruritus) and quality of life. For most categorical endpoints, the Q2W regimen was numerically superior to the Q4W regimen. The safety profile of dupilumab was acceptable; rates of conjunctivitis and injection-site reactions were higher with dupilumab, whereas rates of AD exacerbation and non-herpetic skin infections were higher with placebo.

Funding/Disclosures: ELS has been a consultant for AbbVie, Anacor, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GSK, LEO Pharma, MedImmune, Menlo Therapeutics, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and Valeant, and has received grants/research funding from Amgen, Anacor, Celgene, Chugai Pharma, Eli Lilly, Galderma, Genentech, GSK, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roivant Sciences, Sanofi, Tioga Pharmaceuticals, Vanda. ASP has been an investigator for AbbVie, Anaptysbio, Eli Lilly, Galderma, Incyte, LEO Pharma, Janssen, Novartis, Sanofi, Regeneron Pharmaceuticals, Inc., and a consultant for AbbVie, Amgen, Asana, Dermavant, Dermira, Galderma, Eli Lilly, Forte, LEO Pharma, Matrisys, Menlo, Morphosys/Galapagos, Novartis, Pfizer, Sanofi-Regeneron. ECS has been a consultant for Dermavant, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Inc., and Verrica; has been on the data and safety monitoring board for Novan, GSK, and LEO Pharma; and has been a principal investigator in clinical trials for Janssen, Eli Lilly, Regeneron Pharmaceuticals, Inc., Stiefel, Verrica. MB has received research grants, consulting, and lecture honoraria from Regeneron Pharmaceuticals, Inc. and Sanofi, and has done consulting for Pfizer. DMP has been a consultant for or received honoraria from Bickel Biotechnology, Biofrontera, Celgene, Dermira, DUSA Pharmaceuticals, LEO Pharma, Novartis, Promius Pharma, Regeneron Pharmaceuticals, Inc., Sanofi, TheraVida, and Valeant, has been principal investigator for or received grants/research funding from Abbott, Amgen, Asana BioSciences, Bickel Biotechnology, Celgene, Dermavant Sciences, Eli Lilly, LEO Pharma, Merck, Novartis, Novo Nordisk, Ortho Dermatologics, Peplin, Pfizer, Photocure ASA, Promius Pharma, Regeneron Pharmaceuticals, Inc., Stiefel/GSK, and Valeant, has been on the advisory board member or received honoraria for Pfizer, has been the principal investigator or received honoraria from LEO Pharma and Pfizer, and has been an investigator or received research/grants funding from Promius Pharma. AB has been a scientific adviser and clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Genentech/Roche, GSK, Janssen, LEO Pharma, Meiji, Merck, Novartis, Pfizer, Purdue Pharma, Regeneron Pharmaceuticals, Inc., Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB, Valeant, and Vidac, and has been a paid speaker for Janssen, Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme. TH and HS are employees and might hold stock and/or stock options in the company Sanofi. RZ, MAK, JDD, NMHG, AB are employees and shareholders of Regeneron Pharmaceuticals, Inc.

Efficacy and safety of upadacitinib treatment over 32 weeks for patients with atopic dermatitis from a Phase IIb, randomized, placebo-controlled trial

Presenters: Guttman-Yassky E¹, Silverberg JI², Papp KA³, Hu X⁴, Gu Y⁴, Pangan A⁴, Teixeira HD⁴, Reich K⁵

Affiliations: ¹Icahn School of Medicine at the Mount Sinai Medical Center, New York, NY; ²Northwestern University Feinberg School of Medicine, Chicago, IL; ³K Papp Clinical Research and Probity Medical Research, Waterloo, Canada; ⁴AbbVie Inc, North Chicago, IL; ⁵Dermatologikum Berlin and SCIderm Research Institute Hamburg, Hamburg, Germany

Background/Objective: The selective JAK-1 inhibitor, upadacitinib (UPA), is being investigated for treatment of atopic dermatitis (AD) and other inflammatory indications. Week 16 primary results demonstrated the efficacy of UPA versus placebo. Results from the prespecified, interim analysis at Week 32 are presented.

Methods: Adults with moderate-to-severe AD (Eczema Area and Severity Index [EASI] 16 or greater, body surface area [BSA] 10% or greater, Investigator Global Assessment Scale [IGA] 3 or greater) were randomized in Period 1 (16 weeks) to once-daily (QD) UPA monotherapy 7.5, 15, or 30mg, or placebo. In Period 1, each UPA group was rerandomized by EASI 75 response in Period 2 (72 weeks) in a 1:1 ratio to continue the Period 1 dose or to placebo (withdrawal); the placebo group was rerandomized to UPA 30mg QD or placebo. Starting four weeks after rerandomization (Week 20), rescue therapy with UPA 30mg QD was provided after the first instance of a response with an EASI value less than 50. Missing data and visits after rescue were handled by last-observation-carried-forward (continuous variables) and non-responder-imputation (categorical variables).

Results: Results are reported through Week 32 for patients rerandomized to UPA (placebo/UPA 30mg; UPA 7.5/7.5mg; UPA 15/15mg; UPA 30/30mg). Of the 167 patients randomized in Period 1; 126 were rerandomized in Period 2; all received the study drug. Achievement (% of patients) of EASI 75 at Week 20 and Week 32 was 20.0 percent; 25.0 percent; 33.3 percent*; 73.7 percent* and 80.0 percent*; 18.8 percent; 27.8 percent*; 63.2 percent** (***p<0.001;**p<0.01; *p<0.05 vs. placebo). Mean percent change (negative change indicates improvement) in pruritus Numerical Rating Scale (NRS) at Week 20 and Week 32 was -78.4 percent***; -58.6 percent*; -45.7 percent***; -64.1 percent** and -93.8 percent***; -52.9 percent**; -44.4 percent**; -61.0 percent*** (***p<0.001; **p<0.01; *p<0.05 vs. placebo). The majority of patients who were rerandomized to placebo at Week 16 (placebo/placebo; UPA 7.5mg/placebo; UPA 15mg/placebo; UPA 30mg/placebo) lost response by Week 20. Adverse events (AEs) for patients rerandomized to UPA were reported by seven, four, five, and eight patients; and by one, one, five, and seven patients rerandomized to placebo. Two patients (placebo/UPA 30mg) reported serious AEs and one patient (placebo/UPA 30mg) reported a serious infection. There were no deaths.

Conclusion: Continued treatment with UPA 15mg or UPA 30mg doses demonstrated better response rates versus treatment withdrawal, which resulted in loss of clinical response by Week 20 for the majority rerandomized to placebo; statistically significant differences were observed at Week 32 for achievement of EASI 75 response and a reduction in pruritus NRS. UPA 30mg demonstrated the best efficacy over time in all key endpoints. No new safety concerns were identified.

Funding/Disclosures: EGY received honoraria for consultant services from Abbvie, Allergan, Almirall, Anacor, AnaptysBio, Asana Biosciences, Celgene, Concert, DBV Technologies, Dermira, DS Biopharma, Galderma, Gilead, Glenmark, Immune, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Puricore, Regeneron, Sanofi, Stiefel/GSK, Sun Pharma, Vitae and Ziarco, and received research grants for investigator services from Abbvie, Asana, Celgene, Dermira, Galderma, Glenmark, Immune, Innovaderm, Lilly, Leo Pharma, Medimmune, Novartis, Pfizer, Regeneron, and Vitae. JS received honoraria for ad board, speaker, and consultant services from Abbvie, Eli Lilly, Galderma, GlaxoSmithKline, Kiniksa, Leo, Menlo, Pfizer, Realm-1, Roivant, and Regeneron-Sanofi, and received research grants for investigator services from GlaxoSmithKline. KAP received honoraria or fees for advisory board, speaker and consultant services from AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, and received research grants from AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant. KR received honoraria for advisory board service, speaker service and educational development, and grants for investigator service from AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo, Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Takeda, UCB Pharma, and Xenoport. XH, YG, AP, HT, are full-time employees of AbbVie and may own stock/options. AbbVie funded this study, contributed to its design, and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Jody Bennett of AbbVie.

GBR 830 induces progressive and sustained improvements in atopic dermatitis skin biomarkers and clinical parameters

Presenters: Guttman-Yassky E¹, Pavel A¹, Estrada Y¹, Zhou L¹, Salhi Y², Gudi G², Ca V³, Macoin J⁴, Back J⁴, Wolff G²

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Glenmark Pharmaceuticals Inc; ³Glenmark Pharmaceuticals Ltd, India; ⁴Glenmark Pharmaceuticals SA, Switzerland

Background/Objective: GBR 830 is an investigational, first-in-class, humanized, monoclonal IgG1 antibody specific for inhibiting OX40, a costimulatory receptor on activated T-cells. By blocking binding of OX40 to its ligand OX40L, GBR 830 reduces longevity and efficacy of effector and memory T-cells. OX40 inhibition is suggested to have a potential therapeutic role in T-cell-mediated diseases, including atopic dermatitis (AD), one of the most common inflammatory skin disorders that affects up to 10 percent of adults. This Phase IIa proof-of-concept study in patients with moderate-to-severe AD (NCT02683928) was conducted to investigate the safety of GBR 830, evaluate its effects on AD biomarkers, and generate the first clinical evidence of its biological activity.

Methods: A randomized, double-blind, placebo-controlled, repeated-dose study was conducted in 17 North American centers. There were three study phases: screening (up to 30 days), treatment (Days 1 [baseline] and 29), and follow-up (through Day 85). Treatment randomization was 3:1 to GBR 830 or placebo; patients received two repeated doses (each 10mg/kg, administered intravenously) on Days 1 and 29. Skin punch biopsies were obtained from lesional skin on Days 1, 29, and 71. The corprimary endpoints were treatment-emergent adverse events (TEAEs; frequency, severity) and change from baseline in epidermal hyperplasia and active AD microribonucleic acid (mRNA) expression biomarker signatures measured from lesional skin biopsies. The key secondary endpoint was Eczema Area and Severity Index (EASI) 50 response (50% or greater improvement from baseline) on Days 29 and 71.

Results: Intent-to-treat (ITT)/safety population included 62 subjects: GBR 830, n=46; placebo, n=16. Biological Activity Set (BAS) population included 40 subjects: GBR 830, n=29; placebo, n=11. Demographic and baseline characteristics were generally similar between treatment groups in the ITT/safety BAS populations. TEAEs occurred with similar incidence between treatment groups; most were mild or moderate in intensity. Significant decreases from baseline in OX40+ T-cell and OX40L+DC cellular staining in lesional skin were found with GBR 830 treatment at Day 29 (p<0.05) and Day 71 (p<0.001). Drug versus placebo trended on significance at Day 71 for both markers. GBR 830-treated subjects had significant reductions from baseline in epidermal thickness, K16 mRNA expression, and Ki67+ cells at Days 29 and 71. Changes from baseline with placebo were not significant (thickness, K16) or less pronounced (Ki67+). GBR 830-treated subjects had significant reductions in most mRNA biomarkers of disease activity compared with baseline and placebo. A greater proportion of GBR 830-treated subjects achieved EASI 50 versus placebo at Day 29 (43.6% vs. 20.0%; p=0.2) and Day 71 (76.9% vs. 37.5%; p=0.02). GBR 830-treated subjects demonstrated greater percentage change in EASI from baseline through Day 85 compared to placebo. A positive association was seen between improvements in clinical assessments and changes in tissue AD biomarkers.

Conclusion: GBR 830 was safe and well tolerated, with a similar TEAE profile to placebo. GBR 830 inhibits the OX40/OX40L pathway, as shown through reduced expression of OX40/OX40L in lesional skin. Treatment with GBR 830 resulted in reductions in epidermal hyperplasia, proliferation, and mRNA biomarkers for disease activity, indicating an effect on both the acute and chronic stages of AD. Although the study was not powered for statistical testing, subjects treated with GBR 830 had improvements in AD scores that were consistent with biomarker results. Results of this proof-of-concept study indicate that GBR 830 might be an effective treatment for AD.

Funding/Disclosures: This study was sponsored by Glenmark Pharmaceuticals SA, in La Chaux-de-Fonds, Switzerland. Neither honoraria nor payments were made for authorship. All authors are employees of Glenmark. Medical writing and editorial assistance for this poster was provided by Prescott Medical Communications Group, Chicago, IL, and funded by Glenmark Pharmaceuticals SA.

Patient-reported outcomes in subjects with atopic dermatitis treated with tapinarof cream: results from a Phase IIb, randomized, parallel-group study

Presenters: Paller AS¹, Stein Gold L², Tallman AM³, Rubenstein D⁴

Affiliation: ¹Northwestern University Feinberg School of Medicine, Chicago, IL; ²Henry Ford Medical Center, West Bloomfield, MI; ³Dermavant Sciences, Inc., New York, NY; ⁴Dermavant Sciences, Inc., Durham, NC

Background/Objective: Patients with atopic dermatitis (AD) report impacts on sleep, quality of life, and psychosocial domains (social, academic, and occupational). Here, we present the patient-reported outcomes (PROs) in subjects with AD following treatment with topical tapinarof cream, a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for the treatment of AD and psoriasis.

Methods: In this Phase IIb, double-blind, six-arm, vehicle-controlled, randomized study (NCT02564055), subjects aged 12 to 65 years with AD (Investigator Global Assessment [IGA] score of 3 or greater [moderate to severe] and body surface area [BSA] involvement of 5–35%) were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1.0% once (QD) or twice daily (BID) or vehicle QD or BID for 12 weeks and followed up for four weeks. The previously reported primary endpoint was the proportion of subjects who had an IGA score of 0 or 1 and two-or-more-grade improvement in IGA score from baseline to Week 12. PROs included subject impression of change in severity of AD symptoms and pruritus, change in expanded Patient-Oriented Eczema Measure (POEM) scores from baseline to each study visit and weekly average of Daily Sign and Symptom Severity Diary score from baseline to each study visit. Safety was monitored throughout the study.

Results: Of 247 subjects randomized, 86 percent rated their AD symptoms as moderate or severe at baseline across all treatment groups. At Week 12, 64 percent (1% BID), 59 percent (1% QD), 47 percent (0.5% BID), and 40 percent (0.5% QD) of tapinarof-treated subjects described the severity of their AD symptoms as “very improved” versus 21 percent (BID) and 28 percent (QD) in the vehicle groups. At Week 12, 78 to 87 percent of tapinarof-treated subjects rated the severity of their pruritus as “very improved” or “moderately improved” versus 47 to 64 percent of vehicle-treated subjects. There were improvements in all expanded POEM items from baseline at each study visit in all tapinarof groups, except for weeping or oozing in the 1% BID group. Improvements in weekly average of Daily Sign and Symptom Severity Diary scores were seen for all items across all groups at Week 12. The most common treatment-emergent adverse events (5% or greater) across all treatment groups were nasopharyngitis (8%), folliculitis (7%), and AD (6%).

Conclusion: Subjects with AD treated with tapinarof cream reported an improvement in AD symptoms, including pruritus, after 12 weeks versus vehicle. Overall, tapinarof cream was well tolerated.

Primary results from a Phase IIb, randomized, placebo-controlled trial of upadacitinib for patients with atopic dermatitis

Presenters: Guttman-Yassky E¹, Pangan AL², Silverberg JI³, Thaçi D⁴, Hong CH⁵, Mohamed MEF², Othman AA², Gu Y², Anderson JK², Teixeira HD²

Affiliation: ¹Icahn School of Medicine at the Mount Sinai Medical Center, New York, NY; ²AbbVie Inc, North Chicago, IL; ³Northwestern University Feinberg School of Medicine, Chicago, IL; ⁴University Medical School Schleswig Holstein, Campus Lübeck, Germany; ⁵University British Columbia, Dept. Dermatology and Skin Sciences and Probity Medical Research, Surrey, British Columbia, Canada

Background/Objective: Prednisone is the only United States Food and Drug Administration (FDA)-approved oral systemic treatment for patients with moderate-to-severe atopic dermatitis (AD). A large unmet need exists for oral treatments with higher efficacy and suitable long-term safety. Upadacitinib (UPA), a once-a-day, oral, JAK1-selective inhibitor, is currently being investigated for several inflammatory diseases. The objective of this study was to evaluate safety and efficacy of multiple doses of UPA monotherapy versus placebo for treatment of moderate-to-severe adult AD.

Methods: Included participants were adults aged 18 to 75 years with dermatologist-confirmed AD whose symptoms onset at least one year pre-baseline. Included participants had a documented history of inadequate response to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs) or for whom topical treatments were medically inadvisable. In addition, patients were required to have moderate-to-severe AD at baseline, with an Eczema Area and Severity Index (EASI) score of at least 16, a body surface area (BSA) of at least 10 percent, and an Investigator’s Global Assessment (IGA) score of at least 3. Exclusion criteria were treatment with TCSs, TCIs, or prescription moisturizers with additives within 10 days before baseline, as well as prior exposure to dupilumab or systemic JAK inhibitors. Period 1 of the study was a 16-week, double-blind monotherapy where patients were randomized 1:1:1:1 to receive either UPA 30mg QD (n=42), UPA 15mg once daily (QD) (n=42), UPA 7.5mg QD (n=42), or placebo (n=41). In Period 2, each of these four groups were randomized 1:1 in a 72-week, blinded extension to UPA 30mg QD, UPA 15mg QD, UPA 7.5mg QD, and UPA 30mg, respectively. The primary endpoint was mean percent improvement from baseline in EASI score at Week 16.

Results: At Week 16, the subgroup receiving UPA 30mg experienced the highest mean percent improvement from baseline in EASI score and pruritis, peaking at 82.7 percent and ending at 74.4 percent by Week 16. At Week 16, UPA 30mg was 61.7 percent, UPA 7.5mg was 39.4 percent, and placebo was 23.0 percent. The UPA 30mg group also achieved the best results for EASI-50, EASI-75, EASI-90, and IGA 0/1. Serious (n=4) and severe (n=2) adverse events (AEs) were rare. Common treatment-related adverse events included upper respiratory tract infection, worsening of AD, and acne.

Conclusion: UPA met all primary and secondary efficiency endpoints in AD. No herpes zoster, malignancies, deaths, or cases of pulmonary embolism or deep vein thrombosis were reported. The emerging positive benefit/risk profile observed for UPA in AD resulted in FDA breakthrough designation and supports proceeding with Phase III trials in AD.

Funding/Disclosures: AbbVie Inc. funded this study and participated in the study design, study research, collection, analysis, and interpretation of data, and writing, reviewing, and approving of this publication. All authors had access to the data and participated in the development, review, and approval, and in the decision to submit this publication. EG received honoraria for consultant services from Regeneron, Sanofi, Stiefel/GSK, Pfizer, Galderma, Celgene, Leo Pharma,Dermira, Anacor, AnaptysBio, Glenmark, Novartis, Abbvie, Sun Pharma, Mitsubishi Tanabe, Vitae, Allergan, Almirall, Puricore, Asana Biosciences, Gilead, Concert, Immune, Kyowa Kirin, Ziarco, DS Biopharma, and DBV Technologies, and research grants for investigator services from Regeneron, Pfizer, Abbvie, Celgene, Medimmune, Leo Pharma, Glenmark, Vitae, Innovaderm, Immune, Novartis, Galderma, Dermira, Lilly, and Asana. DT received honoraria for advisory board, speaker, and consultant services from AbbVie, Almiral, Amgen, Bioskin, Boehringer-Ingelheim, Celgene, Galapagos, GSK, Dignity, Dermira, Janssen, Leo, Maruho, Medac, Morphosys, Lilly, Novartis, Pfizer, Regeneron/Sanofi, Sandoz-Hexal, Sun-Pharma, UCB and Xenoport, and research grants for investigator services from AbbVie, Celgene, and Novartis. CH received honoraria for advisory board, speaker, and consultant services from Abbvie, Amgen, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron/Sanofi, Sun Pharma, Valeant, and research grants for investigator services from Abbvie, Akros, Amgen, Cutanea, Celgene, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Reneron/Sanofi, and Roivant Sciences. JS received honoraria for advisory board, speaker, and consultant services from Abbvie, Eli Lilly, Galderma, GlaxoSmithKline, Kiniksa, Leo, Menlo, Pfizer, Realm-1, Roivant, Regeneron-Sanofi, and research grants for investigator services from GlaxoSmithKline. MM, JA, YG, HT, AO, and AP received a salary, stocks, and stock options from AbbVie, as employees.

Tralokinumab significantly reduces Staphylococcus aureus colonization in adult patients with moderate-to-severe atopic dermatitis: results from a Phase IIb, randomized, double-blind, placebo-controlled study

Presenters: Guttman-Yassky E¹, Silverberg JI², Fensholdt J³, Lindegaard KK³, Wollenberg A⁴

Affiliation: ¹Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; ²Departments of Dermatology, Preventive Medicine, and Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL; ³LEO Pharma A/S, Ballerup, Denmark; ⁴Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany

Background/Objective: Atopic dermatitis (AD) is a chronic inflammatory dermatological disorder with a high disease burden. The pathogenesis of AD is multifactorial, involving a cycle of itching, scratching, skin barrier dysfunction, microbial abnormalities and immune-mediated inflammation that is characterized by increased levels of Type 2 cytokines, including interleukin (IL)-13. AD is associated with increased Staphylococcus aureus (S. aureus) colonization. S. aureus might amplify cutaneous inflammatory responses via the release of superantigens, such as toxic shock syndrome toxin-1 and the staphylococcal enterotoxins, which can cause excessive production of T-cell cytokines and toxins (such as alpha-toxin) that can damage keratinocytes, intensifying symptoms and resulting in disease flares. Tralokinumab is an IgG4 fully human monoclonal antibody that works by specifically blocking the effects of IL-13 and has been evaluated in a Phase IIb, randomized, double-blind, placebo-controlled study (NCT02347176) in adults with moderate-to-severe AD. Results of the study showed improvements in the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and SCORing Atopic Dermatitis (SCORAD) scores with tralokinumab on a background of topical corticosteroids (TCS), with a favorable safety and tolerability profile. The objective of the study was to evaluate the effect of tralokinumab treatment on S. aureus colonization in patients with moderate-to-severe AD participating in the Phase IIb study.

Methods: Patients were randomized 1:1:1:1 to receive subcutaneous tralokinumab (45mg, 150mg or 300mg) or placebo every two weeks for 12 weeks on a background of TCS. Eligible patients were aged 18 to 75 years with physician-confirmed diagnosis of AD for at least one year (according to Hanifin and Rajka criteria) and with AD body surface area involvement of 10 percent or greater, EASI score of 12 or greater, SCORAD of 25 or greater, and IGA of 3 or greater. Concomitant Class 3 (World Health Organization) TCS were administered at least once daily during the two-week run-in and as needed throughout the treatment and follow-up periods.

Results: Overall, 204 patients were randomized in the Phase IIb study (placebo, n=51; tralokinumab 45mg, n=50; tralokinumab 150mg, n=51; tralokinumab 300mg, n=52) and included in the intent-to-treat population. Baseline demographics and disease characteristics were similar between treatment groups. In lesional skin at baseline, the number of S. aureus-positive patients was similar across treatment groups (placebo, n=38 [74.5%]; tralokinumab 45mg, n=34 [68.0%]; tralokinumab 150mg, n=37 [74.0%]; tralokinumab 300mg, n=35 [67.3%]). In nonlesional skin at baseline, the number of S. aureus-positive patients was lower compared to lesional skin and varied more across the treatment groups (placebo, n=21 [41.2%]; tralokinumab 45mg, n=16 [32.0%]; tralokinumab 150mg, n=26 [52.0%]; tralokinumab 300mg, n=17 [32.7%]). There was a significant difference in the percentage of S. aureus-positive patients at Week 12 compared to placebo for all three tralokinumab dose groups in both lesional and nonlesional skin, with the greatest differences observed for the tralokinumab 300mg group. The number of patients excluded from the analysis due to the use of prohibited medication was placebo, n=3 (5.9%); tralokinumab 45mg, n=6 (12.0%); tralokinumab 150 mg n=4 (7.8%); tralokinumab 300mg, n=0. The percentage of patients with a shift from S. aureus-positive at baseline to S. aureus-negative at Week 12 was higher, and S. aureus-negative at baseline to S. aureus-positive at Week 12 was lower, in all tralokinumab dose groups compared to placebo in both lesional and nonlesional skin. In lesional skin, the greatest shift in patients from S. aureus-positive to S. aureus-negative was observed for the tralokinumab 300mg group, while in nonlesional skin, the effect was greatest for the tralokinumab 150mg group.

Conclusion: Treatment with tralokinumab on a background of TCS led to significant reductions in S. aureus colonization compared to placebo in both lesional and nonlesional skin of adult patients with moderate-to-severe AD. The results of this study suggest that, in addition to improving disease severity scores, specific neutralization of IL-13 with tralokinumab reduces S. aureus colonization, potentially leading to fewer skin infections and AD flares. The effect of tralokinumab 300mg on the reduction of S. aureus colonization will be further examined in a large Phase III study in adults with moderate-to-severe AD (NCT03131648).

Funding/Disclosures: The tralokinumab Phase IIb study was sponsored by MedImmune. This poster was sponsored by LEO Pharma. Medical writing and editorial support was provided by Stephanie Rippon and Jane Beck from Complete HealthVizion, funded by LEO Pharma.

CUTANEOUS ONCOLOGY

Improvement of risk assessment in cutaneous melanoma (CM) by a prognostic 31-gene expression profile (31-GEP) test over AJCC-based staging alone

Presenters: Prado G¹, Cook RW², Covington KR², Monzon FA², Rigel D³

Affiliations: ¹National Society for Cutaneous Medicine, New York, NY; ²Castle Biosciences, Inc., Friendswood, TX; ³New York University School of Medicine, New York, NY

Background/Objective: Accurate assessment of recurrence and metastatic risk is critical for cutaneous melanoma (CM) patient management decisions. Patients initially diagnosed with Stage I to II disease account for a large proportion of those who develop metastases and die from CM, suggesting a need for additional prognostic tools. The 31-Gene Expression Profile (GEP) test has been shown to stratify risk of developing metastasis within five years into low risk (Class 1; 1A lowest risk) and high risk (Class 2; 2B highest risk) and improves prognostic assessment for patients with melanoma. The test has been demonstrated to guide follow-up intensity, sentinel lymph node biopsy decisions, surveillance use, and possible adjuvant therapy. The current study evaluated performance of the 31-GEP test and its ability to improve accuracy of risk estimates over American Joint Committee on Cancer (AJCC) staging alone.

Methods: Archival primary CM tumor samples from 18 centers in the United States (N=690, Stage I–III) along with clinicopathological and outcomes data were collected under an Institutional Review Board (IRB)-approved protocol. Stage I to II cases were restaged according to AJCC 8th edition. Class 1A and 2B-predicted melanoma-specific survival (MSS) outcomes for each stage were compared to rates associated with AJCC stage only. The Kaplan-Meier method and log-rank tests were used to assess five-year recurrence-free (RFS), distant metastasis-free survival (DMFS), and MSS rates.

Results: The 690-case cohort demonstrated stage-specific MSS rates matching those from the AJCC 8th edition cohort (±1.2%). Class 2B cases had significantly worse RFS, DMFS, and MSS compared to Class 1A cases (p<0.0001). Across all stages, a 31-GEP result identified cases with improved (Class 1A) and worsened (Class 2B) prognoses compared to the risks predicted by clinicopathologic stage alone. Stage I patients have a five-year AJCC MSS rate of 98 percent, with the 690-case cohort rate at 98.5 percent. While Stage I Class 1A cases had a MSS rate of 99.6 percent (Stage IA equivalent), a Class 2B result was associated with a MSS rate between AJCC Stage IIA–IIB risk (MSS=89.5%). Stage II patients have a five-year AJCC MSS rate of 90 percent, with the 690-cohort rate at 90.7 percent. Among these cases, the MSS rate of Class 1A cases was greater than 99 percent (Stage IA equivalent), while for Class 2B cases, it was 84.7 percent (MSS between Stage IIB–IIC). Stage III patients have five-year MSS rates of 77 percent and 75.8 percent in the AJCC and 690-cohorts, respectively. Stage III Class 1A cases had an MSS rate of 94.8 percent (similar to Stage IIA), and Class 2B cases demonstrated a rate of 61.2 percent (worse than Stage IIIC).

Conclusion: This study demonstrates that 31-GEP testing adds prognostic value by further stratifying risk for melanoma-related mortality to improve risk estimates beyond AJCC staging alone.

Funding: This study was sponsored by Castle Biosciences, Inc., which provided funding to contributing centers for tissue and clinical data retrieval.

Phase II study of cemiplimab, a human monoclonal anti-PD-1 antibody, in patients with advanced basal cell carcinoma (BCC) who experienced progression of disease on, or were intolerant of, prior hedgehog pathway inhibitor (HHI) therapy

Presenters: Lewis KD¹, Fury MG², Stankevich E³, Mathias M², Mohan KK², Li S³, Nunnink K², Perry C², Narwal A³

Affiliations: ¹School of Medicine, University of Colorado Denver, Aurora, CO; ²Regeneron Pharmaceuticals, Inc., Tarrytown, NY; ³Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ

Background/Objective: Basal cell carcinoma (BCC) is the most common cancer worldwide. There is no approved agent to treat advanced BCC in patients who experience disease progression on, or who are intolerant of, Hedgehog pathway inhibitors (HHIs). Cemiplimab (REGN2810), an anti-PD-1 antibody, has demonstrated encouraging efficacy and favorable tolerability in a Phase I study of patients with advanced malignancies (NCT02383212).

Methods: This is an ongoing Phase II, nonrandomized, two-group, multicenter study of cemiplimab in patients with advanced BCC who experienced disease progression on, or are intolerant of, HHI therapy (NCT03132636). Group 1 will enroll patients with both nodal and distant metastatic BCC. Group 2 will enroll patients with locally advanced BCC who are not candidates for surgery or radiotherapy. Cemiplimab will be administered intravenously every three weeks in all patients. The primary objective of the study is to evaluate overall response rate (ORR) as determined by central review. The ORR will be assessed separately for patients in Group 1 or Group 2 (by RECIST 1.1 for radiology and modified World Health Organization [WHO] criteria for photography). Up to 137 patients will be enrolled. For Group 1, 50 patients are required to provide at least 85-percent power to reject a null hypothesis of an ORR of 15 percent at a two-sided significance level of five percent if the true ORR is 34 percent. For Group 2, 80 patients are required to provide at least 85-percent power to reject a null hypothesis of an ORR of 20 percent at a two-sided significance level of five percent if the true ORR is 35 percent. An additional five percent in sample size will account for patient withdrawals.

Results: This study is ongoing.

Funding/Disclosures: Regeneron Pharmaceutical Inc. and Sanofi sponsored the study. KDL received research funding and consulting fees from Regeneron Pharmaceuticals, Inc.; MGF is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; ES is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; MM is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; KKM is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; SL is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; KN is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; CP is an employee and shareholder of Regeneron Pharmaceuticals, Inc.; AN is an employee and shareholder of Regeneron Pharmaceuticals, Inc.

Primary analysis of Phase II results for cemiplimab, a human monoclonal anti-PD-1 antibody, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC)

Presenters: Rischin D¹, Migden MR², Chang ALS³, Chung CH⁴, Dunn LA⁵, Guminski A⁶, Hauschild A⁷, Hernandez-Aya L⁸, Hughes BGM⁹, Lewis KDM¹⁰, Lim AM¹¹, Modi B¹², Schadendorf D¹³, Schmults CD¹⁴, Booth J¹⁵, Li S¹⁵, Mohan K¹⁵, Stankevich E¹⁶, Lowy I¹⁵, Fury M¹⁵

Affiliations: ¹Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; ²Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX; ³Department of Dermatology, Stanford University School of Medicine, CA; ⁴Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center and Research Institute, FL; ⁵Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, NY; ⁶Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia; ⁷Schleswig-Holstein University Hospital, Kiel, Germany; ⁸Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, MO; ⁹Royal Brisbane & Women’s Hospital and University of Queensland, Brisbane, Australia; ¹⁰University of Colorado Denver, School of Medicine, CO; ¹¹Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia; ¹²Division of Dermatology, City of Hope, CA; ¹³University Hospital Essen, Essen and German Cancer Consortium, Germany; ¹⁴Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA; ¹⁵Regeneron Pharmaceuticals Inc., Tarrytown, NY; ¹⁶Regeneron Pharmaceuticals Inc., Basking Ridge, NJ

Background/Objective: Cutaneous squamous cell carcinoma (CSCC) is the second-most-common skin cancer after basal cell carcinoma. Cemiplimab is the only United States Food and Drug Administration (FDA)-approved treatment for patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Cemiplimab (REGN2810) treatment at 3mg/kg every two weeks (Q2W) demonstrated encouraging preliminary activity in CSCC in a Phase I study. We present the primary analysis of the metastatic CSCC (mCSCC) cohort from the pivotal Phase II study (NCT02760498; data cut-off date: October 27, 2017).

Methods: Patients with mCSCC (defined as nodal and/or distant) received cemiplimab 3mg/kg Q2W intravenously over 30 minutes. Tumor measurements were performed every eight weeks (Q8W). The primary objective was to evaluate overall response rate (ORR; complete response [CR]+partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified World Health Organization [WHO] criteria for photos). Duration of response (DOR) was a key secondary endpoint. Durable disease control rate (DDCR) was defined as stable disease or response for 16 weeks or more.

Results: Fifty-nine patients were enrolled (54 women/5 men; median age: 71.0 years [range: 38–93]; ECOG performance status: 0 and 1 in 23 and 36 patients, respectively). Thirty-three patients (55.9%) had received prior systemic therapy, and 50 patients (84.7%) had received prior radiotherapy. Median duration of follow-up was 7.9 months (range: 1.1–15.6). ORR by central review was 47.5-percent (95% confidence interval [CI]: 34.3–60.9; 4 CRs and 24 PRs). Responses were observed irrespective of prior systemic therapy. Median DOR has not been reached. Only three responding patients had subsequent disease progression at the time of data cut-off. DDCR was 61 percent (95% CI: 47.4–73.5). Median time to response was 1.9 months (range: 1.7–6.0). The most common adverse events (AEs) regardless of attribution (all grades, Grade 3 or greater) were diarrhea (27.1%, 1.7%), fatigue (23.7%, 1.7%), and nausea (16.9%, 0.0%). Immune-related AEs Grade 3 or greater (per investigator assessment) occurred in 10.2 percent of patients.

Conclusion: In the largest prospective study reported in patients with mCSCC, cemiplimab 3mg/kg Q2W showed substantial activity and durable responses. The safety profile was comparable with other anti-programmed cell death protein 1 (PD-1) agents.

Funding/Disclosures: Regeneron Pharmaceutical Inc. and Sanofi sponsored the study. DR reports institutional clinical trial funding from Regeneron Pharmaceuticals, Inc., during the conduct of the study; institutional clinical trial funding and grants from Roche Genentech and GSK; and institutional clinical trial funding and uncompensated scientific committee and advisory board from Merck (MSD), Bristol Myers-Squibb, and Amgen. MRM reports honoraria/travel expenses from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, Eli Lilly, and Sun Pharma; and institutional research funding from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Eli Lilly. ALSC reports grant from Regeneron Pharmaceuticals, Inc., during the conduct of the study. CHC reports institutional research funding from Regeneron Pharmaceuticals, Inc., during the conduct of the study; and personal fees from Bristol Myers Squibb and Astra Zeneca. LAD reports institutional fees from Regeneron Pharmaceuticals, Inc. during the conduct of the study, as well as research support from Eisai Pharmaceuticals. AG reports personal fees and non-financial support (advisory board and travel support) from BMS and Sun Pharma; personal fees (advisory board) from Merck KgA, Eisai, and Pfizer; non-financial (travel) support from Astellas, and clinical trial unit support from PPD Australia. AH reports institutional grants, speaker’s honoraria and consultancy fees from Amgen, Bristol-Myers Squibb, MSD/Merck, Pierre Fabre, Provectus, Roche, and Novartis; institutional grants and consultancy fees from Merck Serono, Philogen, and Regeneron Pharmaceuticals, Inc.; and consultancy fees from OncoSec. LHA reports institutional fees from Regeneron Pharmaceuticals, Inc. during the conduct of the study; institutional fees from BMS, Merck, Amgen, Roche, Novartis, Immunocore, Merck-EMD, Corvus, Polynoma, and Genentech. BGMH reports participation as advisory board member for Bristol-Myers Squibb, Borrhinger Ingelhiem, Merck Sharp & Dohme, Roche, AstraZeneca, Pfizer, and Eisai. KDL reports grant and consulting fees from Regeneron Pharmaceuticals, Inc. during the conduct of the study. AML was supported by the Department of Health (W.A) / Raine Medical Research Foundation Clinician Research Fellowship. BM declares no conflict of interest. DS reports institutional patients’ fees from Regeneron Pharmaceuticals, Inc., during the conduct of the study; adboard honorarium fees Amgen and Leo Pharma; speaker fee from Boehringer Ingelheim; adboard, speaker honorarium and patients’ fees from Roche, Novartis, BMS, and Merck-EMD; adboard and speaker honorarium fees from Incyte and Pierre Fabre; adboard honorarium and patients’ fees from MSD, steering cie honorarium fees from 4SC, adboard fees from AstraZeneca, Pfizer, and Array; and adboard and patients’ fees from Philiogen. CDS reports participating as steering committee member with Castle Biosciences, grants (basal cell staging) from Genentech, grants (cutaneous squamous cell carcinoma [Investigational programmed cell death-1 drug]) from Regeneron Pharmaceuticals, Inc., outside the submitted work. JB is an employee of Regeneron Pharmaceuticals, Inc. SL is an employee of Regeneron Pharmaceuticals, Inc. KM is an employee of Regeneron Pharmaceuticals, Inc. ES is an employee and shareholder of Regeneron Pharmaceuticals, Inc. IL is an employee and shareholder of Regeneron Pharmaceuticals, Inc. MF is an employee and shareholder of Regeneron Pharmaceuticals, Inc.

HYPERHYDROSIS

Clinical management of anticholinergic adverse events with topical glycopyrronium tosylate, a treatment for primary axillary hyperhidrosis

Presenters: Pariser D¹, Gopalan R², Drew J², Green L³

Affiliations: ¹Eastern Virginia Medical School/Virginia Clinical Research, Inc., Norfolk, VA; ²Dermira, Inc., Menlo Park, CA; ³George Washington University School of Medicine, Washington, DC

Background/Objective: Glycopyrronium tosylate (GT) is a topical anticholinergic recently approved by the United States Food and Drug Administration (FDA) for use in primary axillary hyperhidrosis in patients nine years of age or older (glycopyrronium cloth, 2.4%). GT safety and efficacy were evaluated in two replicate, vehicle (VEH)-controlled, four-week, Phase III trials (ATMOS-1 [NCT02530281] and ATMOS-2 [NCT02530294]). The safety and tolerability profile of GT and the clinical management of adverse events (AEs) associated with anticholinergics are presented.

Methods: Patients nine years of age or older with primary axillary hyperhidrosis were randomized 2:1 to GT or VEH applied once daily. AEs, including relationship to study drug, were recorded throughout the trials. Blurred vision, mydriasis, and symptoms associated with urinary retention/hesitation were identified as AEs of special interest (AESIs) based on their known association with anticholinergic compounds. Dose interruptions were allowed for intolerable treatment-related AEs and mandated for treatment-related blurred vision and symptoms associated with urinary hesitancy, obstruction, or retention.

Results. In the pooled population, 463 patients were randomized to GT and 234 to VEH; 426 (92.0%) and 225 (96.2%) completed the trials, respectively. Individual trial and pooled data for GT versus VEH showed significantly higher Axillary Sweating Daily Diary (ASDD)/ASDD-Children (ASDD-C) Item 2 response rates (4-point-or-greater improvement in sweating severity) and reduced sweat production at Week 4 compared to baseline (coprimary endpoints). The incidence of AEs in the pooled population was similar to the individual trials. Consistent with individual studies, a majority of AEs in the pooled population were mild or moderate in severity and infrequently led to discontinuation (3.7% GT, 0.4% VEH). Commonly reported AEs with GT were dry mouth (24.2% GT, 5.6% VEH), application site pain (8.7% GT, 9.5% VEH), mydriasis (6.8% GT, 0% VEH), and oropharyngeal pain (5.7% GT, 1.3% VEH). Management of AEs included drug interruption (6.3% GT, 2.2% VEH) and drug reduction (5.2% GT, 0% VEH). AESIs occurred in 13.3 percent (61/459) of GT-treated patients and zero VEH treated patients; most were considered related to study drug, of mild to moderate severity, and transient. Approximately half of patients with AESIs had their event resolve without drug interruption or withdrawal. In general, AESIs resolved within 3 to 14 days, despite continued application of study drug or did not recur upon treatment resumption. Nine events (three blurred vision, two urinary hesitation, and single events of mydriasis, nocturia, pollakiuria, and urinary retention) lasted for more than 14 days. For patients with mydriasis or blurred vision, over half had the event resolve without study drug interruption or discontinuation. Eight patients had both mydriasis and blurred vision (all concurrent), and for six of eight patients, the events resolved during drug interruption or following discontinuation.

Conclusion: GT was well tolerated, and AEs were mostly mild/moderate and infrequently led to discontinuation or dosing changes.

Funding/Disclosures: Not provided

Short- and long-term efficacy and safety of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: post-hoc pediatric subgroup analyses from the Phase III studies

Presenters: Hebert A¹, Glaser D², Green L³, Werschler WP⁴, Forsha DW⁵, Drew J⁶, Gopalan R⁶, Pariser DM⁷

Affiliations: ¹UTHealth McGovern Medical School, Houston, TX; ²St. Louis University, St. Louis, MO; ³George Washington University School of Medicine, Washington, DC; ⁴Premier Clinical Research, Spokane, WA; ⁵Jordan Valley Dermatology and Research Center, West Jordan, UT; ⁶Dermira, Inc., Menlo Park, CA; ⁷Eastern Virginia Medical School & Virginia Clinical Research, Inc., Norfolk, VA

Background/Objective: Glycopyrronium tosylate (GT) is a topical anticholinergic recently approved by the United States Food and Drug Administration (FDA) for use in primary axillary hyperhidrosis in patients nine years of age or older (glycopyrronium cloth, 2.4%). GT reduced sweating severity and sweat production and improved quality of life in two replicate, vehicle (VEH)-controlled, four-week, Phase III studies in primary axillary hyperhidrosis (ATMOS-1 [NCT02530281], ATMOS-2 [NCT02530294]) and the 44-week open-label study (ARIDO [NCT02553789]). To better understand short and long-term response in pediatric patients (9 years or older, 16 years or younger) versus older patients (>16 years), pooled post-hoc analyses were performed.

Methods: Efficacy assessments included the Axillary Sweating Daily Diary (ASDD/ASDD-C [Children]) Item 2 responder rate (4-point-or-greater improvement in sweating severity; 4-week trials), median change in sweat production, Hyperhidrosis Disease Severity Scale (HDSS) responder rate (2 grade or greater improvement) and change from baseline (cfb) in Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI). Safety assessments included treatment-emergent adverse events (TEAEs). Post-hoc comparisons were descriptive.

Results: Of 697 in the pooled population, 44 were between nine and 16 years of age (GT, n=25; VEH, n=19). In pediatric and older subgroups, completer rates were 96.0 percent and 100 percent for GT versus 91.8 percent and 95.8 percent for VEH, respectively. Of 564 (86.6%) entering ARIDO, 38 were pediatric. In the four-week trials, similar results were observed in pediatric and older subgroups across efficacy measures at Week 4. Pooled ASDD/ASDD-C Item 2 responder rates for both age subgroups (pediatric and older) were 59.9 percent and 60.2 percent (GT) versus 13.0 percent and 28.8 percent (VEH), respectively. Median changes in sweat production (mg) were -64.2 and -80.6 (GT) versus 53.7 and 62.0 (VEH), respectively. HDSS responder rates were 61.3 percent and 58.7 percent for GT and 20.3 percent and 26.0 percent for VEH., respectively Mean cfb in CDLQI (GT, -8.1; VEH, 1.9) was similar to DLQI (GT, 8.4; VEH, -4.7). Outcomes in the double-blind trials showed increasing benefit with a maximal response at Week 4. In the open-label trial, where all patients received GT, and improvements were maintained in both subgroups for up to 44 weeks for all measures (pediatric and older: median change in sweat production was -50.3 and 75.1, HDSS responder rates were 56.7% and 63.6%, and cfb in CDLQI/DLQI was -6.2 and -8.7, respectively). GT was generally well tolerated; TEAEs in pediatric patients were qualitatively similar to those in the older subgroup, and most were mild, infrequently leading to discontinuation.

Conclusion: Topical GT applied once-daily for up to 48 weeks was generally well tolerated, reduced sweating severity, decreased sweat production, and improved quality of life, with similar findings in children and adults that are consistent with the overall population.

Funding/Disclosures: Not provided

PRURITUS

Impact of serlopitant on prurigo nodularis measured by the prurigo activity score

Presenters: Ständer S¹, Kwon P², Weisshaar E³

Affiliations: ¹University Hospital Münster, Münster, Germany; ²Menlo Therapeutics Inc, Redwood City, CA; ³University of Heidelberg, Heidelberg, Germany

Background/Objective: Prurigo nodularis (PN), also described as chronic prurigo of the nodular type, is a chronic skin condition characterized by intensely pruritic nodular lesions. Treatment of PN is challenging due to limited data from randomized controlled trials and lack of currently approved therapies specifically for PN. Goals of therapy are to reduce pruritus and allow PN lesions to heal. However, limited data are available on the impact of antipruritic treatment on healing of PN lesions. In a recent, eight-week study in patients with PN, tghe neurokinin 1 receptor (NK1R) antagonist, serlopitant, reduced pruritus compared with placebo and was well tolerated (NCT02196324). This study is one of the largest randomized, controlled trials conducted to date on the treatment of patients with PN. A secondary endpoint of this study was mean change from baseline in PN skin lesions as measured by the prurigo activity score (PAS). The objective of the study was to assess the impact of treatment with serlopitant on healing of PN lesions as measured by the PAS in this study.

Methods: Secondary analysis of a Phase II, double-blind study of 128 patients with chronic, treatment-refractory PN randomized 1:1 to receive oral serlopitant 5mg or placebo once daily for eight weeks. The study population was adults with chronic PN (duration or 6 weeks or longer) that was unresponsive to topical glucocorticoid or antihistamine therapies and a Visual Analog Scale-Pruritus score of 70 or greater. The endpoints were impact of therapy on PAS at Week 8 for the following outcomes: percentage of lesions healed (0–24%, 25–49%, 50–74%, 75–99%, 100%); percentage of lesions with excoriations/crusts (0%, 1–25%, 26–50%, 51–75%, >75%); number of lesions (0, 1–19, 20–100, >100); distribution of lesions (disseminated, localized, intermediate); and size of biggest and representative lesions.

Results: The percentage of patients with 50 percent or more of PN lesions healed, as measured by PAS, increased from 23.5 percent at baseline to 49.2 percent after eight weeks for serlopitant-treated patients, and from 34.9 percent at baseline to 44.7 percent after eight weeks for placebo-treated patients. In addition, 5.3 percent of patients in the serlopitant group, 100 percent of the PN lesions were healed after eight weeks, compared to zero percent for the placebo. The percentage of patients with 25 percent or less of PN lesions with excoriations or crusts increased from 7.8 percent at baseline to 33.3 percent after eight weeks for serlopitant-treated patients, and from 11.1 percent at baseline to 23.4 percent after eight weeks for placebo-treated patients. In addition, 7.0 percent of patients in the serlopitant group had no excoriated/crusted PN lesions after eight weeks, compared to zero percent for the placebo. The percentage of patients with less than 20 PN lesions increased from 9.4 percent at baseline to 17.5 percent after eight weeks for serlopitant-treated patients, and from 9.5 percent at baseline to 12.8 percent after eight weeks for placebo-treated patients. In addition, 3.5 percent of patients in the serlopitant group had no PN lesions after eight weeks, compared to zero percent for the placebo. Distribution of PN lesions was disseminated in 100 percent of patients in both treatment groups at baseline. After eight weeks of serlopitant treatment, distribution remained disseminated in most (94.7%) patients, was localized (only 1 or 2 areas affected) in two patients (3.5%), and was intermediate (>2 areas affected but not generalized) in one patient (1.8%). In the placebo group, distribution after eight weeks remained disseminated in 97.9 percent of patients and was localized in one patient (2.1%). Size of the biggest and representative PN lesions tended to decrease over the course of treatment in both groups.

Conclusion: Serlopitant-treated patients showed a greater level of improvement in percentage of healed and excoriated/crusted lesions and in number and dissemination of pruriginous lesions over the course of the study, though healing of PN lesions is expected to take longer than eight weeks. The efficacy, safety, and tolerability of serlopitant for the treatment of pruritus in patients with PN will be further evaluated in a Phase III study (NCT03546816). Because the Phase III study will have a longer treatment duration (10 weeks), the results might clarify if the observed improvement in healing of PN lesions will continue with longer treatment duration.

Funding/Disclosures: This study was sponsored by Menlo Therapeutics Inc. Medical writing and editorial support was provided by Amy Agbonbhase, PhD, of the Lockwood Group (Stamford, CT) in accordance with Good Publication Practice (GPP3) guidelines and funded by Menlo Therapeutics Inc.

PSORIASIS

Effects of brodalumab on anxiety and depression in patients with psoriasis: results from a Phase III, randomized, controlled clinical trial

Presenters: Gooderham M¹, Feldman SR², Harris S³, Jacobson A⁴, Israel RJ³

Affiliations: ¹SKiN Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, Ontario, Canada; ²Wake Forest University School of Medicine, Winston-Salem, NC; ³Bausch Health, Bridgewater, NJ; ⁴Ortho Dermatologics, Bridgewater, NJ

Background/Objective: Anxiety and depression occur more frequently among patients with psoriasis than the general population. Treatment of psoriasis might reduce mental health comorbidities. Our objective was to evaluate changes in anxiety and depression over 52 weeks in a pivotal Phase III clinical trial (AMAGINE-1) of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody.

Methods: Adult patients with moderate-to-severe plaque psoriasis were randomized to brodalumab (140 or 210mg) or placebo every two weeks (Q2W) during a 12-week induction phase. At Week 12, patients on brodalumab who did not achieve success (static physician’s global assessment [sPGA] score 1 or less) and patients in the placebo group were allocated to treatment with brodalumab 210mg Q2W for the remaining 40 weeks. Patients receiving brodalumab who achieved success were rerandomized to their induction dose of brodalumab or placebo. Beginning at Week 16, all rerandomized patients who experienced return of disease (sPGA 3 or greater) qualified for retreatment with brodalumab. Hospital Anxiety and Depression Scale (HADS) scores were measured at baseline and at Week 12, 24, 36, and 52. The HADS questionnaires each consist of seven items scored using a scale ranging from 0 to 3 (0–21 total). A HADS score less than eight is considered normal.

Results: Six hundred and sixty-one patients were started on brodalumab 210mg (n=222), brodalumab 140mg (n=219), or placebo (n=220) Q2W. Baseline HADS scores were similar across treatment groups. At Week 12, patients who switched from placebo to brodalumab 210mg Q2W had a mean (standard error [SE]) HADS anxiety score of 6.2 (0.3) and depression score of 5.4 (0.3), which improved to 4.5 (0.3) and 3.1 (0.3), respectively, at Week 52. Conversely, patients who switched from brodalumab 210mg Q2W to placebo had a mean (SE) HADS anxiety score of 4.4 (0.4) and depression score of 2.9 (0.3) at Week 12, which worsened to 6.5 (3.5) and 3.5 (1.5), respectively, at Week 52. Findings in patients with moderate-to-severe HADS scores (11 or greater) at baseline were similar to those in the overall patient population.

Conclusion: Brodalumab reduces the burden of mental health comorbidities associated with psoriasis, such as depression and anxiety.

Funding/Disclosures: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom under the direction of the authors and was funded by Ortho Dermatologics. MG has been an advisory board member, clinical investigator, and/or speaker for AbbVie, Inc; Akros, Inc; Amgen Inc; Boehringer Ingelheim; Celgene Corporation; Dermira, Inc; Genentech, Inc; GlaxoSmithKline; Janssen Pharmaceuticals; Kyowa Hakko Kirin Co, Ltd; LEO Pharma; Eli Lilly & Co; MedImmune, Inc; Merck & Co, Inc; Novartis Pharmaceuticals Corporation; Pfizer, Inc; Regeneron Pharmaceuticals, Inc; Sanofi Genzyme; Sun Pharma; Takeda Pharmaceuticals, Inc; UCB; and Bausch Health. SRF has served as a speaker or consultant or has received research support from Galderma; GlaxoSmithKline/Stiefel Laboratories; Almirall; LEO Pharma, Inc; Baxter; Boeringer Ingelheim; Mylan; Celgene Corporation; Pfizer, Inc; Bausch Health; Taro; AbbVie, Inc; Cosmederm; Anacor Pharmaceuticals; Astellas Pharma, Inc; Janssen Pharmaceuticals; Eli Lilly & Co; Merck & Co, Inc; Merz; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc; Novan, Inc; Parion Sciences, Inc; Qurient Co, Ltd; National Biological Corporation; Caremark; Advance Medical; Suncare Research Laboratories; Informa; UpToDate; and the National Psoriasis Foundation. He has also served as a consultant for Guidepoint Global, Gerson Lehrman, and other consulting organizations. He is the founder and majority owner of www.DrScore.com, and the founder and part owner of Causa Research. SH and RJI are employees of Bausch Health and hold stock and/or stock options in the company. AJ is an employee of Ortho Dermatologics and holds stocks and/or stock options in Bausch Health.

Efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis of the scalp: results of a Phase III, multicenter, randomized, placebo-controlled, double-blind study

Presenters: Van Voorhees A¹, Stein Gold L², Lebwohl M³, Strober B⁴, Lynde C⁵, Tyring S⁶, Cauthen A⁷, Sofen H⁸, Zhang Z⁹, Paris M⁹, Wang Y⁹

Affiliations: ¹Eastern Virginia Medical School, Norfolk, VA; ²Henry Ford Health System, West Bloomfield, MI; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴University of Connecticut, Farmington, CT, and Probity Medical Research, Waterloo, Ontario, Canada; ⁵Lynde Institute for Dermatology, Markham, Ontario, Canada; ⁶Center for Clinical Studies, Webster, TX; ⁷MidState Skin Institute, Ocala, FL; ⁸Dermatology Research Associates, Los Angeles, CA; ⁹Celgene Corporation, Summit, NJ

Background/Objective: Many patients with psoriasis report that they are most bothered by symptoms in difficult-to-treat, highly visible, pruritic areas, such as the scalp. Topical therapies can be difficult to apply to the scalp area. We evaluated efficacy and safety of apremilast, an oral PDE4 inhibitor indicated for treatment of moderate-to-severe plaque psoriasis, in patients with moderate-to-severe scalp psoriasis.

Methods: This was a Phase III, multicenter, double-blind, placebo (PBO)-controlled study in patients with moderate-to-severe plaque psoriasis of the scalp (scalp Physician Global Assessment [ScPGA] 3 or greater [moderate or greater]; psoriasis-involved scalp surface area [SSA] 20% or greater) with inadequate response/intolerance to one or more topical therapy and moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] 12 or greater, psoriasis-involved body surface area [BSA] 10% or greater; static PGA [sPGA] 3 or greater [moderate or greater]). Patients were randomized to apremilast 30mg twice daily (BID) (APR) or PBO through Week 16 and continued or switched to APR through Week 32. The primary endpoint, proportion of patients achieving ScPGA response at Week 16 (score of 0 [clear] or 1 [almost clear] with 2-point-or-greater reduction from baseline) with APR versus PBO, and secondary endpoints (proportion of patients with 4-point-or-greater improvement from baseline in whole body itch and scalp itch numeric rating scale (NRS) scores and change from baseline at Week 16 in Dermatology Quality of Life Index [DLQI] total score) were evaluated using the Cochran-Mantel-Haenszel method for binary endpoints and analysis of covariance model for continuous endpoints with missing values imputed using the multiple imputation method.

Results: In all, 303 patients were randomized (APR n=201, PBO n=102). Baseline demographics were generally comparable between APR and PBO groups (mean [SD] age, 47.0 [15.0] and 46.7 [15.2] years; mean [SD] disease duration, 15.7 [12.4] and 14.8 [11.3] years). At baseline, mean (SD) values for APR and PBO, respectively, were as follows: SSA, 61.9 percent (27.2) and 58.2 percent (26.4); scalp itch NRS, 6.6 (2.5) and 6.7 (2.4); BSA, 19.0% (10.8) and 21.2% (14.8); whole body itch NRS, 7.2 (2.3) and 7.2 (2.0); and DLQI, 12.6 (7.0) and 12.6 (7.2). At Week 16, significantly more patients treated with APR versus PBO achieved the primary endpoint (43.4% vs. 13.8%, P<0.0001). In addition, in patients treated with APR, 47.0 percent and 45.3 percent achieved four-or-greater-point improvement from baseline in scalp itch and whole body itch NRS scores versus 21.3 percent and 22.5 percent of patients treated with PBO (P</=0.0001 for both comparisons). Statistically significant improvements with APR versus PBO were observed on both itch NRS measures as early as Week 2 (scalp: 26.0% vs. 11.5%; whole body: 20.5% vs. 3.5%; P<0.01 and P<0.0001, respectively). Improvement from baseline in DLQI score at Week 16 was significantly greater with APR versus PBO (least-square means, -7.1 vs. -4.2, P<0.0001). Common AEs, occurring in five percent or more of patients in either treatment group, were diarrhea (30.5% and 10.8%), nausea (21.5% and 5.9%), headache (11.5% and 4.9%), and vomiting (5.5% and 2.0%) with APR and PBO, respectively.

Conclusion: Findings demonstrated the efficacy of APR in patients with moderate-to-severe psoriasis of the scalp. AEs were consistent with the known safety profile of apremilast.

Funding: Celgene Corporation

Efficacy and safety of an oral, selective TYK2 inhibitor, BMS-986165, in patients with moderate-to-severe plaque psoriasis: a Phase II, randomized, placebo-controlled trial

Presenters: Papp K¹, Gordon K², Thaçi D³, Morita A⁴, Gooderham M⁵, Foley P⁶, Girgis IG⁷, Kundu S⁷, Banerjee S⁷

Affiliations: ¹K Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada; ²Medical College of Wisconsin, Milwaukee, WI; ³University of Lübeck, Lübeck, Germany; ⁴Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ⁵SKiN Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, Ontario, Canada; ⁶The University of Melbourne, St Vincent’s Hospital Melbourne & Probity Medical Research, Skin & Cancer Foundation Inc, Melbourne, Victoria, Australia; ⁷Bristol-Myers Squibb, Princeton, NJ

Background/Objective: Tyrosine kinase 2 (TYK2) activates signal transducer and activator of transcription (STAT)-dependent signalling pathways of interleukin-23 and Type I interferons, which are involved in psoriasis pathology. BMS-986165 is an oral, selective TYK2 inhibitor. A 12-week, dose-ranging, placebo-controlled, Phase II study (NCT02931838) investigated efficacy and safety of BMS-986165 in patients with moderate-to-severe plaque psoriasis.

Methods: Adults with plaque psoriasis for six or more months and moderate-to-severe disease (body surface area [BSA] 10% or greater, Psoriasis Area and Severity Index [PASI] 12 or greater, static Physician Global Assessment [sPGA] 3 or greater) were randomized to 1 of 5 oral doses of BMS-986165 (3mg every other day [QOD], 3mg every day [QD], 3mg twice daily [BID], 6mg BID, 12mg QD) or placebo. Primary endpoint: PASI 75 at Week 12.

Results: 267 patients were randomized and treated. At baseline, mean age of subjects was 45 years, 73 percent were men with a median disease duration of 15 years and prior biologic experience of 43 percent; mean baseline BSA was 23 percent, mean PASI score 18. Overall, characteristics were balanced among treatment arms. At Week 12, the percentages of patients who achieved PASI 75 were 7 percent with placebo and 9 percent, 39 percent*, 69 percent**, 67 percent**, 75 percent** with BMS-986165 3mg QOD, 3mg QD, 3mg BID, 6mg BID, 12mg QD, respectively (*p<0.05, **p<0.0001 vs. placebo). The percentages of patients who achieved PASI 90 were two percent, seven percent, 16 percent*, 44 percent**, 44 percent**, and 43 percent**. For sPGA score 0/1, percentages were seven percent, 20 percent, 39 percent*, 76 percent**, 64 percent**, 75 percent**. Percentages of patients with DLQI score 0/1 were four percent, 16 percent, 16 percent, 42 percent**, 60 percent**, 64 percent**. Efficacy was observed in biologic-naïve and biologic-experienced patients. Treatment-emergent adverse events (TEAEs) were reported in 51 percent (placebo), 59 percent (3mg QOD), 55 percent (3mg QD), 64 percent (3mg BID), 80 percent (6mg BID), and 77 percent (12mg QD) of patients. There were five serious AEs reported, none considered drug related: two events in one placebo patient (hemorrhagic anemia, hemorrhoidal hemorrhage); one event in one patient each in the 3mg QOD (gastroenteritis rotavirus), 3mg QD (eye injury), and 3mg BID (dizziness) groups. No cases of herpes zoster or tuberculosis were reported. Most common TEAEs across arms (ranges): nasopharyngitis (2–16%), headache (4–9%), diarrhea (2–9%), nausea (2–9%), upper respiratory tract infections (0–9%). AEs were generally mild to moderate and resulted in drug discontinuation in four percent of placebo patients and 2 to 7 percent of patients across active doses. There were no significant changes in liver enzymes, blood counts, or lipid levels.

Conclusion: BMS-986165 demonstrated statistically greater efficacy compared with placebo in PASI 75 (primary endpoint), PASI 90, and sPGA 0/1 responses at doses of at least 3mg QD, with dose-related PASI 75 responses peaking at 75 percent. The compound was well tolerated with generally mild to moderate AEs that rarely resulted in discontinuation. Further evaluation of BMS-986165 as a treatment for psoriasis is warranted. two Phase III trials in psoriasis are ongoing (POETYK PSO-1/2: NCT03624127, NCT03611751).

Funding: Study supported by Bristol-Myers Squibb

Efficacy of risankizumab compared with placebo across subgroups in patients with moderate-to-severe plaque psoriasis: integrated analyses from three Phase III trials

Presenters: Lebwohl M¹, Ghislain PD², Kerdel F³, Gu Y⁴, Valdes JM⁴, Thompson EHZ⁵, Lynde C⁶

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; ²UCL St. Luc, Brussels, Belgium; ³Florida Academic Dermatology Centers, Miami, FL; ⁴AbbVie Inc., North Chicago, IL; ⁵AbbVie Inc., Redwood City, CA; ⁶The Lynde Centre for Dermatology and Probity Medical Research, Markham, Ontario, Canada

Introduction: Interleukin-23 (IL-23) plays a key role in the development and maintenance of psoriatic lesions by regulating multiple effector cytokines. Risankizumab (RZB) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-23 by binding to its p19 subunit. The superior efficacy of RZB compared to placebo (PBO) as well as acceptable safety and tolerability profile have been demonstrated in three independent Phase III, randomized, double-blind, PBO-controlled trials. The objective of this analysis was to evaluate the integrated efficacy of RZB compared to PBO across subgroups of patients with moderate-to-severe plaque psoriasis.

Methods: Data from three Phase III studies in patients with moderate-to-severe plaque psoriasis were integrated over the 16-week PBO-controlled period. Patients stratified by weight and prior tumor necrosis factor inhibitor (TNFi) exposure at randomization received either 150mg RZB (n=1005) at Weeks 0 and 4 or matched PBO (n=300). Coprimary efficacy endpoints assessed for consistency at Week 16 across subgroups were Psoriasis Area and Severity Index (PASI) 90 and static Physician Global Assessment (sPGA) 0/1 responses. Missing data were imputed as nonresponders. Treatment comparisons were conducted by Cochran-Mantel-Haenszel test stratified by study, baseline weight (100kg or less vs. 100kg or greater), and prior exposure to TNFi (0 vs. 1 or greater).

Results: Among 1,305 patients included in this integrated analysis, baseline demographics and disease characteristics were generally similar between the two treatment arms. Mean age was 48.1 years and mean weight was 90.8kg; 70.3 percent of patients were men. Mean baseline PASI and body surface area (BSA) were 20.3 and 26.1 percent, respectively. Median baseline PASI score was 18.0, while baseline sPGA was moderate in 80.2 percent of patients. A history of diagnosed or suspected psoriatric arthritis (PsA) was reported in 30.9 percent of patients. At Week 16, RZB-treated patients achieved significantly higher PASI 90 and sPGA 0/1 response rates compared with PBO-treated patients (P<0.001 for both endpoints across all subgroups; regardless of baseline demographics or disease characteristics. The efficacy of RZB in each of the subpopulations was comparable to the overall efficacy in the pooled population.

Conclusion: Treatment with RZB was associated with superior efficacy compared with PBO in adult patients with moderate-to-severe plaque psoriasis, regardless of baseline demographics or disease characteristics.

Funding/Disclosures: ML has received grants as an investigator from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Kadmon Corporation, LEO Pharma, MedImmune, Novartis, Sun Pharma, and Valeant, and has been a paid consultant for Boehringer Ingelheim and Leo Pharma. PDG has received honoraria from AbbVie, Amgen, BMS, Celgene, Eli-Lilly, Flen, Galderma, Janssen, Leo, Maruho, Meda, Menarini, MSD, Novartis, Pfizer, and UCB for participation as a consultant, investigator, speaker, and for participation on ad boards. FK has received honoraria from AbbVie, Amgen, Celgene, Janssen, Leo, Pfizer, Eli Lilly, Novartis, and Stiefel for participation as a speaker; and received grants from AbbVie, Amgen, AstraZeneca, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer for participation as an investigator. YG, JMV, and EHZT are full-time employees of AbbVie and may own stock/options. CL has received honoraria as a principal investigator, speaker, and/or consultant from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, and Valeant. AbbVie and Boehringer Ingelheim funded the UltIMMa-1 (NCT02684370), UltIMMa-2 (NCT02684357), and IMMhance (NCT02672852) studies; Boehringer Ingelheim contributed to its design and participated in data collection, AbbVie performed the data analysis, and participated in interpretation of the data, and both participated in writing, review, and approval of the abstract. AbbVie, Boehringer Ingelheim, and the authors thank all study investigators for their contributions and the patients who participated in this study. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie.

Efficacy of tildrakizumab in patient subgroups across one Phase IIb and two Phase III trials in patients with moderate-to-severe chronic plaque psoriasis

Presenters: Poulin Y^1,2, Ramon M³, Rosoph L⁴, Weisman J⁵, Mendelsohn AM⁶, Parno J⁶, Rozzo SJ⁶, Lee P⁷

Affiliations: ¹Hospital Center of Laval University, Hôpital Hôtel-Dieu de Québec, Québec City, Quebec, Canada; ²Dermatological Research Center of Metropolitan Quebec, Québec City, Quebec, Canada; ³Department of Dermatology, Rambam Health Campus, Haifa, Israel; ⁴North Bay Dermatology Centre, North Bay, Ontario, Canada; ⁵Medical Dermatology Specialists, Inc., Atlanta, GA; ⁶Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁷Center for Clinical Studies, Webster, TX

Background/Objective: Tildrakizumab is a high-affinity, anti-interleukin-23p19 monoclonal antibody indicated for use in the treatment of moderate-to-severe plaque psoriasis. Understanding potential efficacy differences between patient subgroups might help to identify the most appropriate patients for tildrakizumab treatment.

Methods: Pooled data from one Phase IIb and two Phase III, randomized, controlled trials were used to evaluate the efficacy of tildrakizumab in specific subgroups. The tildrakizumab Phase IIb (P05495 [NCT01225731]) and Phase III (reSURFACE 1 [NCT01722331] and reSURFACE 2 [NCT01729754]) trials included patients with moderate-to-severe chronic plaque psoriasis (10% or greater body surface area [BSA], Physician’s Global Assessment [PGA] score 3 or greater, and Psoriasis Area and Severity Index [PASI] score 12 or greater). In P05495, patients received placebo or tildrakizumab 5, 25, 100, or 200mg at Weeks 0 and 4 and every 12 weeks thereafter. In reSURFACE 1 and 2, patients received placebo or tildrakizumab 100 or 200mg at Weeks 0 and 4 (Part 1, Weeks 0–12) and every 12 weeks thereafter. This post-hoc analysis included all patients from the full analysis set who received placebo or tildrakizumab 100 or 200mg at Weeks 0 and 4. The following subgroups were analyzed: age (<65, 65 years or older), sex, race (Asian, white, black/African American, other), psoriatic arthritis (yes, no), failure (yes, no) of at least one traditional systemic treatment (methotrexate, cyclosporine, or phototherapy), prior biologic use (yes, no), and weight (90kg or less, greater than 90kg).

Results: The percentages of patients in each subgroup who achieved a 75-percent-or-greater reduction in PASI score from baseline (PASI 75 responders) in the tildrakizumab 100 or 200mg groups were compared to placebo-treated patients at Week 12 using nonresponder imputation of missing data. Among patients randomized in P05495 (N=355), reSURFACE 1 (N=772), and reSURFACE 2 (N=1090), the differences in the percentages of PASI 75 responders between tildrakizumab- and placebo-treated patients at Week 12 were 56.4 percent and 59.3 percent for tildrakizumab 100 and 200mg, respectively. PASI 75 response rates were numerically greater in patients who weighed 90kg or more and in those with no psoriatic arthritis. This was also the case for patients younger than 65 years of age compared to those 65 years of age or older, but the small numbers in this subgroup limit interpretation. There was no clear or consistent influence on efficacy in the other subgroups, including prior traditional or biologic agent use.

Conclusion: Tildrakizumab 100mg and 200mg efficacy was consistent across subgroups but was slightly improved in patients with lower body weight and no psoriatic arthritis. Previous biologic use was not associated with a lower response rate.

Funding: The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Analyses were presented at the DERM 2018 NP/PA Conference, July 19–22, 2018, Las Vegas, NV.

An evaluation of clinical and quality-of-life outcomes with apremilast treatment in clinical studies in patients with moderate-to-severe (ESTEEM) or moderate (UNVEIL) plaque psoriasis and scalp or nail involvement

Presenters: Korb Ferris L¹, Cohen DJ², Cirulli J³, Petric R³, Burds PF³, Poulin Y⁴

Affiliations: ¹University of Pittsburgh, Pittsburgh, PA; ²Skin Care Physicians of Georgia, Macon, GA; ³Celgene Corporation, Summit, NJ; ⁴Laval University, Quebec, Canada

Background/Objective: Patients with psoriasis might have lesions in highly visible, difficult-to-treat areas, such as the scalp and nails, which can cause embarrassment and severely impact quality of life (QOL) and daily functioning. The efficacy and safety profile of apremilast—an oral, small-molecule phosphodiesterase 4 inhibitor—was evaluated in patients with moderate-to-severe psoriasis (psoriasis-involved body surface area [BSA] 10% or greater, static Physician Global Assessment [sPGA] 3 or greater, Psoriasis Area and Severity Index [PASI] 12 or greater) in the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) Phase III clinical trial program and in a Phase IV study in systemic- and biologic-naive patients with moderate psoriasis (BSA 5–10%, sPGA=3), Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL). The current analysis characterizes clinical and QOL outcomes observed among patients in the ESTEEM and UNVEIL trials who had scalp or nail involvement at baseline.

Methods: ESTEEM 1 and 2 (NCT01194219 and NCT01232283) were similarly designed Phase III multicenter, randomized, double-blind, placebo (PBO)-controlled studies of apremilast 30mg twice daily (APR) in patients with moderate-to-severe plaque psoriasis. UNVEIL (NCT02425826) was a Phase IV, multicenter, randomized, double-blind, placebo-controlled study in biologic- and systemic-naive patients with moderate plaque psoriasis. Full details of the study design, inclusion and exclusion criteria, patient population, and primary safety and efficacy results for the ESTEEM and UNVEIL trials have been described in detail previously. Clinical efficacy and QOL were evaluated based on mean Dermatology Life Quality Index (DLQI) scores at Weeks 16 and 32, achievement of a DLQI score of 0 or 1 (minimal impact of psoriasis on QOL) at Weeks 16 and 32, achievement of five-point improvement in DLQI score at Weeks 16 and 32, a NAPSI score of 0 (nail clearance) at Weeks 16 and 32, and an ScPGA score of 0 (clear) or 1 (minimal) at Weeks 16 and 32. Post-hoc analyses of the proportions of patients meeting the response criteria were evaluated descriptively, with missing data handled using the last-observation-carried-forward (LOCF) methodology.

Results: There were 1,255 patients in ESTEEM 1 and 2 and 221 patients in UNVEIL. Despite greater psoriasis-involved BSA in patients in ESTEEM versus UNVEIL, mean DLQI score at baseline was generally similar, indicative of a similar, significant impact of psoriasis on QOL in patients with moderate-to-severe psoriasis (ESTEEM) and patients with moderate psoriasis (UNVEIL). At baseline, most patients in ESTEEM had moderate-to-very-severe scalp psoriasis (n=832), greater than 60 percent had nail involvement, and 1,100 patients had scalp or nail involvement. In contrast, fewer UNVEIL patients had moderate-to-very-severe scalp psoriasis (n=98), nail psoriasis (n=83), or scalp or nail psoriasis (n=146) at baseline. Mean (SD) BSA at baseline among patients with scalp or nail involvement was 26.5 percent (15.1) and 24.8 percent (15.2) in ESTEEM and 7.2 percent (1.8) and 7.1 percent (1.6) in UNVEIL with PBO versus APR, respectively. At Week 16, among patients with moderate-to-severe psoriasis (ESTEEM) or moderate psoriasis (UNVEIL) who had moderate-to-very-severe scalp psoriasis at baseline, ScPGA score of 0 or 1 was achieved by greater proportions of patients receiving APR versus PBO, regardless of the extent of whole-body psoriasis. At Week 32, ScPGA score of 0 or 1 was maintained with APR treatment in the open-label treatment phase. At Week 16, among patients with moderate-to-severe psoriasis (ESTEEM) who had nail psoriasis at baseline, Nail Psoriasis Severity Index (NAPSI) 0 was achieved by more patients receiving APR versus PBO. Among patients with moderate psoriasis (UNVEIL) who had nail psoriasis at baseline, the proportion of patients who achieved NAPSI 0 was comparable between the APR and PBO groups. Mean DLQI scores improved at Week 16 in patients treated with APR; at Week 32, improvement was maintained in patients who continued APR and emerged in patients who were randomized to PBO and then switched to APR at Week 16. At Week 16, a five-or-greater-point improvement from baseline in DLQI score was achieved by greater proportions of patients receiving APR versus PBO. At Week 32, a five-or-greater-point improvement from baseline in DLQI score was maintained in the open-label APR treatment phase.

Conclusion: Patients with moderate-to-severe psoriasis (ESTEEM) and patients with moderate psoriasis (UNVEIL) reported similar levels of QOL impairment at the baseline visit, despite substantial differences in extent and severity of psoriasis. In both ESTEEM and UNVEIL, greater proportions of patients with baseline nail and scalp psoriasis demonstrated complete clearance of nail psoriasis and clear or minimal involvement of scalp psoriasis with APR treatment compared with PBO. With APR treatment, more patients reported that psoriasis had no effect on their QOL compared with patients in the PBO group at Week 16, which was maintained with open-label APR treatment at Week 32.

Funding/Disclosures: LKF is an consultant and/or investigator for AbbVie, Amgen, Eli Lilly, Castle Biosciences, DermTech, Janssen, LEO Pharma, Novartis, Pfizer, and Regeneron. DJC has no conflicts of interest to disclose. JC, RP, and PFB are employees of Celgene Corporation. YP has received grants, board membership fees, and/or speaker fees from AbbVie, Amgen, Baxter, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, EMD Serono, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, and UCB Pharma.

An evaluation of clinical and quality-of-life outcomes with apremilast treatment for up to 52 weeks in ESTEEM 1 patients with moderate-to-severe plaque psoriasis classified as PASI-75 nonresponders

Presenters: Jullien D¹, Weiss JS², Cirulli J³, Petric R³, Abramovits W⁴

Affiliations: ¹Edouard Herriot Hospital—Department of Dermatology and Venereology, Lyon, France; ²Gwinnett Dermatology PC, Snellville, GA; ³Celgene Corporation, Summit, NJ; ⁴Dermatology Treatment and Research Center, Dallas, TX

Background/Objective: Among patients with plaque psoriasis, improvements in patient-reported measures, such as pruritus and quality of life (QOL), are not captured by traditional measures of clinical efficacy, such as Psoriasis Area and Severity Index (PASI)-75 response. The Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) evaluated the efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis. The current analysis characterizes clinical and QOL outcomes observed among ESTEEM 1 patients who did not achieve a PASI-75 response at both Week 32 and Week 52 (PASI-75 nonresponders) yet chose to continue apremilast treatment during this period (Weeks 32 to 52).

Methods: ESTEEM 1 (ClinicalTrials.gov: NCT01194219) was a Phase III, multicenter, randomized, double-blind, placebo (PBO)-controlled study of apremilast 30mg twice daily (APR) in patients with moderate-to-severe plaque psoriasis. Full details of the study design, inclusion and exclusion criteria, patient population, and primary safety and efficacy results for ESTEEM 1 have been described in detail previously. The current analysis included only those patients who were PASI-75 nonresponders at both Week 32 and Week 52 who continued APR treatment (PBO/APR/APR and APR/APR/APR). Using a linear mixed model for repeated measures, adjusted mean percentage change from baseline in PASI and pruritus visual analog scale (VAS) scores and mean change in Dermatology Life Quality Index (DLQI) score by time point were examined. The proportions of patients achieving a PASI-50 response at Weeks 16, 32, and 52 were summarized.

Results: A total of 203/844 ESTEEM 1 patients (24.1%) (PBO/APR/APR n=69; APR/APR/APR n=134) who were randomized at baseline were PASI-75 nonresponders at Weeks 32 and 52. At Week 32, patients who were PASI-75 nonresponders could add topical or phototherapy at the discretion of the investigator. Baseline PASI scores were comparable between the two groups of nonresponders (APR/APR/APR baseline mean standard deviation [SD]: 17.8 [5.5]; PBO/APR/APR baseline mean [SD]: 19.4 [6.7]). An approximately 50-percent reduction from baseline in PASI score was maintained from Weeks 12 to 52 in patients receiving APR/APR/APR (improvement range: -48.2 to -55.1%), and from Weeks 24 to 52 in patients receiving PBO/APR/APR (improvement range: -49.3 to -55.7%). Among patients who did not achieve a PASI-75 response at both Week 32 and Week 52, a greater proportion of patients receiving APR versus PBO achieved a PASI-50 response at Week 16. The majority of the patients remaining on APR (APR/APR/APR) or switching from PBO to APR (PBO/APR/APR) achieved a PASI-50 response at Weeks 32 and 52. Baseline pruritus VAS scores were comparable between the two groups of nonresponders (APR/APR/APR baseline mean [SD]: 65.7 [23.7]; PBO/APR/APR baseline mean [SD]: 64.7 [25.3]). In patients treated with APR, pruritus VAS scores were reduced from baseline by approximately one-third from Weeks 4 to 52 in patients receiving APR/APR/APR (improvement range: -29.8% to -38.3%), and from Weeks 20 to 52 in patients receiving PBO/APR/APR (improvement range: -27.7 to -36.9%). At baseline, DLQI scores (mean [SD]) were comparable between the APR/APR/APR (12.0 [7.1]) and PBO/APR/APR (12.4 [5.8]) groups. In patients treated with APR, improvement from baseline in DLQI score by greater than five points was demonstrated in the APR/APR/APR group from Week 4 through Week 52 (range of mean improvement: -5.9 to -7.7). The PBO/APR/APR group, during APR treatment (range of mean improvement: -5.8 to -6.8).

Conclusion: In ESTEEM 1 patients who did not achieve a PASI-75 response, many achieved clinically meaningful improvements in itch and QOL. Approximately 60 percent of patients achieved a PASI-50 response at Week 52 with continuous APR treatment. The PASI-75 response threshold might not always capture all patients who derive therapeutic benefit from treatment. Concurrent assessment of improvements in partial skin clearance, pruritus, and QOL might more reliably indicate clinically meaningful benefit with APR treatment.

Funding/Disclosures: DJ has received personal fees from AbbVie, Celgene Corporation, Eli Lilly, Janssen, LEO Pharma, Novartis, and Sanofi. JSW has been a researcher, speaker, and/or consultant for AbbVie, Amgen, Celgene Corporation, Janssen, LEO Pharma, Novartis, Promius, and Valeant/Ortho. JC and RP are employees of Celgene Corporation. WA is advisory board, speaker, consultant, and/or investigator for AbbVie, Akros, Allergan, Amgen, Anacor Pharm, Aqua Pharma, Celgene Corporation, Centocor, Conversant Bio, Dermavant, Eli Lilly, Exeltis, Galderma, Genentech, Glenmark, GSK, Innocutis, Innovaderm, Janssen Biotech, LEO Pharma, MediMetriks, Merck, Novartis, Novan, Novum, Otsuka, Parexel, PharmaDerm, Perrigo, Pfizer, Premier, Promius, Prothena, PuraCap, Quinnova, Ranbaxy, Regeneron, Rho, Sanofi, Serono, Taro, Teva, Tioga, Theorem, Tolmar, UBC, Valeant, and XenoPort.

Impact of prior treatment history on efficacy of risankizumab compared with placebo in patients with moderate-to-severe plaque psoriasis: integrated analyses from three Phase III trials

Presenters: Strober B¹, Lambert J², Gu Y³, Thompson EHZ⁴, Valdecantos WC³, Menter A⁵

Affiliations: ¹University of Connecticut Health Center and Probity Medical Research, Farmington, CT; ²Department of Dermatology, Ghent University Hospital, Gent, Belgium; ³AbbVie Inc., North Chicago, IL; ⁴AbbVie Inc., Redwood City, CA; ⁵Division of Dermatology, Baylor University Medical Center, Dallas, TX

Background/Objective: Interleukin-23 (IL-23), an important regulator of multiple effector cytokines, plays a pivotal role in the development and maintenance of psoriatic lesions. Risankizumab (RZB) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-23 by binding to its p19 subunit. The superior efficacy of RZB compared to placebo (PBO) and ustekinumab, as well as its acceptable safety and tolerability profile, have been demonstrated in three Phase III, randomized, double-blind, PBO- and active-comparator-controlled trials. The objective of this analysis is to report the integrated efficacy of RZB compared to PBO by prior treatment history in patients with moderate-to-severe plaque psoriasis.

Methods: Data from three Phase III studies (IMMhance, UltIMMa-1, and UltIMMa-2) in patients with moderate-to-severe plaque psoriasis were integrated over the 16-week PBO-controlled period. Patients stratified by weight and prior tumor necrosis factor inhibitor (TNFi)-exposure at randomization received either 150mg RZB (n=1,005) at Weeks 0 and 4 or matching PBO (n=300). The consistency of Psoriasis Area and Severity Index (PASI) 90 and static Physician Global Assessment (sPGA) clear or almost clear (sPGA 0/1) responses at Week 16 was assessed in subgroups of patients by prior psoriasis treatment history. The reason for prior treatment discontinuation was generally patient-reported. Missing data were imputed as nonresponders. Treatment comparisons were conducted by Cochran-Mantel-Haenszel test stratified by study, baseline weight (100kg or less vs. greater than 100kg), and prior exposure to TNFi (0 vs. 1 or greater).

Results: Mean baseline PASI and BSA were 20.3 and 26.1 percent, respectively. A history of diagnosed or suspected psoriatic arthritis (PsA) was reported in 30.9 percent of patients. Of the 1,305 patients included in this integrated analyses, 19.7 percent were naïve to all treatment except topical therapy and 30.0 percent were naïve to systemic therapy. Prior psoriasis therapy received included phototherapy (31.2%), photochemotherapy (8.7%), nonbiologic systemic therapy (47.8%), and biologic therapy (44.8%). TNFi therapy was reported in 28.1 percent of patients, while 29.6 percent received non-TNFi biologic therapy. A total of 218 patients reported failure of one or more prior biologic therapy; a majority was failure of at least one prior TNFi therapy. At Week 16, RZB-treated patients achieved significantly higher PASI 90 and sPGA 0/1 response rates compared to PBO-treated patients (P<0.001 for both endpoints across all subgroups), regardless of previous psoriasis treatment history. The efficacy of RZB in each of the subpopulations was comparable to the overall efficacy in the pooled population.

Conclusion: Treatment with RZB was associated with superior efficacy compared to PBO in adult patients with moderate-to-severe plaque psoriasis, regardless of previous psoriasis treatment history, including prior biologic failure.

Funding/Disclosures: AbbVie and Boehringer Ingelheim funded the IMMhance (NCT02672852), UltIMMa-1 (NCT02684370), and UltIMMa-2 (NCT02684357) studies; Boehringer Ingelheim contributed to its design and participated in data collection, AbbVie performed the data analysis and participated in interpretation of the data, and both participated in writing, review, and approval of the abstract. AbbVie, Boehringer Ingelheim, and the authors thank all study investigators for their contributions and the patients who participated in this study. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie. BS has received honoraria as a consultant from AbbVie, Almirall, Amgen, Astra Zeneca, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo, Medac, Menlo Therapeutics, Novartis, Ortho Dermatologics/Valeant, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB Pharma; scientific director for the CORRONA-NPF Psoriasis Registry. JL serves as an investigator and/or consultant for AbbVie, Celgene, Janssen, Lilly, Leo Pharma Novartis, Pfizer, and UCB. YG, EHZT, and WCV are full-time employees of AbbVie and might own stock/options. AM has received grants and honoraria from AbbVie, Amgen, Janssen Biotech, Inc., and LEO Pharma for service on an advisory board, as consultant, investigator, and speaker; received grants and honoraria from Allergan for service on an advisory board and as a consultant and from Eli Lilly for service on an advisory board, as a consultant and investigator; received grants and honoraria from Boehringer Ingelheim for service on an advisory board and as an investigator; received grants and honoraria from Novartis, and Pfizer for service as a consultant and investigator; received grants from Celgene, Dermira, Merck, Neothetics, Regeneron, and Syntrix for service as an investigator; and received honoraria from Galderma for service as a consultant.

Incidence of cardiovascular events among tildrakizumab-treated patients with moderate-to-severe plaque psoriasis: pooled data from three large, randomized, clinical trials

Presenters: Bissonnette R¹, Fernández-Peñas P², Puig L³, Mendelsohn AM⁴, Rozzo SJ⁴, Menter AM⁵

Affiliations: ¹Innovaderm Research, Montreal, Quebec, Canada; ²Department of Dermatology, Westmead Hospital, Westmead, and Sydney Medical School, University of Sydney, Sydney, NSW, Australia; ³Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; ⁴Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁵Division of Dermatology, Baylor Scott & White, and Texas A&M College of Medicine, Dallas, TX

Background/Objective: Observational studies suggest that patients with moderate-to-severe psoriasis might have an increased risk of major adverse cardiovascular (CV) events (MACE). We assessed the incidence of CV events during Phase II and III trials of tildrakizumab (TIL), a high-affinity, humanized, immunoglobulin G1-kappa, anti-interleukin-23p19 antibody for moderate-to-severe chronic plaque psoriasis.

Methods: This pooled analysis included data from patients in P05495 (Phase IIb; NCT01225731) and reSURFACE 1 and 2 (Phase III; NCT01722331 and NCT01729754) who received placebo (PBO) or TIL 100 or 200mg at Weeks 0, 4, and every 12 weeks thereafter, and were followed up to Week 52 (P05495/reSURFACE 2) or Week 64 (reSURFACE 1). reSURFACE 2 included an additional arm of etanercept (ETN) 50mg administered twice per week for the first 12 weeks and then once per week up to Week 28. PBO controls were included up to Week 16 (P05495) or Week 12 (reSURFACE 1 and 2). Safety data from the full-trial periods and Year 1 of the extensions were analyzed. In this safety pool, patients with multiple treatments were counted in each assigned treatment group after starting a different treatment. Extensions to Phase III studies are ongoing. MACE comprised nonfatal myocardial infarction (MI), stroke, and CV deaths confirmed as CV or sudden. Confirmed composite-adjudicated CV (CACV) events included MACE; unstable angina; coronary revascularization; resuscitated cardiac arrest; and fatal or nonfatal thrombotic, embolic, or ischemic CV events.

Results: The pooled safety population included 588 patients who received PBO, 1,083 who received TIL 100mg, 1,041 TIL 200mg, and 313 ETN. The numbers of patients with CACV events (exposure-adjusted rate, measured as the number of patients with events/100 patient-years) were comparable for the TIL 100mg (4 [0.40]) and 200mg (8 [0.86]) groups versus PBO (1 [0.46]) and ETN (1 [0.65]). Three deaths were adjudicated as MACE unrelated to study treatment, all in patients with preexistent CV risk factors (e.g., hypertension): aneurysm (TIL 200mg) and respiratory arrest and MI (both TIL 100mg).

Conclusion: In the extension, across TIL 100 and 200mg groups (n=1,237), only seven patients had CACV events (0.60%); no deaths were due to CV events. In the TIL clinical program, the incidence of CV events was low and comparable across TIL treatment groups and versus PBO and ETN.

Funding: The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Analyses were presented at the Fall Clinical Dermatology Conference, October 18–21, 2018, Las Vegas, NV.

Incidence of infections in clinical trials of tildrakizumab for moderate-to-severe chronic plaque psoriasis

Presenters: Crowley JJ¹, Sturgill-Koszycki S², Menter AM³, Mendelsohn AM⁴, Li Q⁵

Affiliations: ¹Bakersfield Dermatology, Bakersfield, CA; ²Previously of Sun Pharmaceutical Industries, Inc., Princeton, NJ; ³Division of Dermatology, Baylor Scott & White, and Texas A&M College of Medicine, Dallas, TX; ⁴Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁵Merck & Co., Inc., Kenilworth, NJ

Background/Objectives: Risk of infection is a concern with biologic cytokine inhibitor treatments. This analysis assessed infections during Phase II and III trials of tildrakizumab (TIL), a high-affinity, humanized, immunoglobulin G1-kappa, anti-interleukin-23p19 monoclonal antibody for moderate-to-severe chronic plaque psoriasis.

Methods: Patients were randomized in P05495 (Phase II; NCT01225731), reSURFACE 1 (Phase III; NCT01722331), and reSURFACE 2 (Phase III; NCT01729754). In Part 1 (Weeks 1–16) of P05495, patients received subcutaneous placebo or TIL 5mg, 25mg, 100mg, or 200mg at Weeks 0 and 4, and were rerandomized to various TIL doses in Part 2 (Weeks 16–52). In Part 1 (Weeks 1–12) of reSURFACE 1 and 2, patients received subcutaneous placebo, TIL 100mg, or TIL 200mg at Weeks 0 and 4. Patients were rerandomized in Part 2 (Weeks 12–28) and Part 3 (Weeks 28–64 in reSURFACE 1 and Weeks 28–52 in reSURFACE 2). Etanercept 50mg was an active control in Parts 1 and 2 of reSURFACE 2. Treatment-emergent adverse event data pools (n=2081) for the placebo-controlled and full trial periods (52 weeks for P05495/reSURFACE 2; 64 weeks for reSURFACE 1) were analyzed.

Results: Severe infections met the regulatory definition of a serious adverse event (AE) or required intravenous antibiotics. In the placebo-controlled period, the incidence of infections was comparable for placebo and TIL 100mg and 200mg (23%, 23%, and 22%, respectively); all were comparable with etanercept (24%). The incidence of severe infections was low for all treatment groups (range, 0.0–0.3%). In the full trial period, exposure-adjusted rates (patients/100 patient-years) for infections were lower with TIL 100mg and 200mg (48.9 and 52.6, respectively) than with placebo and etanercept (79.5 and 86.0, respectively). Exposure-adjusted rates for severe infections were 0.91, 1.10, 1.61, and 1.96 for placebo, TIL 100mg, TIL 200mg, and etanercept, respectively. In all, 33 severe infections were identified (respiratory: tildrakizumab 100mg, 4 events; tildrakizumab 200mg, 2 events; placebo and etanercept, 0 events; skin: placebo, 3 events; TIL 100mg, 3 events; TIL 200mg, 6 events; etanercept, 2 events; gastrointestinal: TIL 100mg, 4 events; TIL 200mg, 5 events; placebo and etanercept, 0 events; urinary tract: TIL 200mg, 1 event; etanercept, 1 event; placebo and TIL 100mg, 0 events). One patient had bone tuberculosis (TIL 200mg; original purified protein derivative test was negative), and one sepsis event (TIL 200mg) occurred seven months after TIL treatment ended.

Conclusion: Infection rates with TIL treatment were low and comparable with placebo and etanercept during the placebo-controlled period. By Weeks 52/64, exposure-adjusted rates remained low for all groups.

Insights into psoriasis disease severity and treatment efficacy using patient-level Psoriasis Area and Severity Index (PASI) scores from tildrakizumab Phase III clinical trials

Presenters: Ellis C¹, Korman N², Murphy FT^3,4, Spelman L^5,6, Mendelsohn AM⁷, Parno J⁷, Rozzo SJ⁷, Yamauchi PS⁸

Affiliations: ¹Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI; ²Case Western Reserve University and University Hospital Cleveland Center, Cleveland, OH; ³Altoona Arthritis & Osteoporosis Center, Duncansville, PA; ⁴Villanova University, Villanova, PA; ⁵Veracity Clinical Research, Woolloongabba, Queensland, Australia; ⁶Probity Medical Research, Waterloo, Ontario, Canada; ⁷Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁸David Geffen School of Medicine at UCLA, Los Angeles, CA

Introduction: Typical psoriasis clinical trial efficacy endpoints, such as 90-percent-or-greater reduction in Psoriasis Area and Severity Index score (PASI 90) response, provide little information on disease activity and are less relevant to patients than low PASI scores. We performed a post-hoc analysis of pooled data from two tildrakizumab (TIL) Phase III trials to ascertain the value of patient-level PASI scores and dichotomous PASI improvement rates as estimators of residual disease following treatment.

Methods: In reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754), patients received TIL 100mg (n=616) or 200mg (n=622) at Weeks 0, 4, and then every 12 weeks, or placebo (n=309) at Week 0 and Week 4 followed by rerandomization at Week 12 and treatment with TIL 100mg or 200mg at Week 12 and Week 16. PASI score distributions were compared using a two-sample asymptotic Kolmogorov–Smirnov (KS) test of observed data at Weeks 0, 4, 12, and 28.

Results: At Week 0, median PASI score was 18.0 across groups, indicating that a PASI score 1.8 or less was needed to achieve PASI 90 response in 50 percent of the patients. Differences in PASI score distributions between TIL and placebo were significant at Weeks 4, 8, and 12 (all KS test P<0.001). Median PASI scores decreased to 11.0 at Week 4 and 3.0 at Week 12 in both TIL groups, and PASI scores were significantly correlated with percentage PASI changes in both TIL groups (P<0.0001). At Week 12, PASI scores 1.0 or less and 2.0 or less were achieved by 32 percent and 46 percent of patients (TIL 100mg) and by 29 percent and 47 percent of patients (TIL 200mg), respectively, whereas 38 and 37 percent achieved PASI 90 response with TIL 100 and 200mg. At Week 28, median PASI scores were 2.0 and 1.0 in the TIL 100mg and 200mg treatment arms, respectively; PASI scores 1.0 or less and 2.0 or less were achieved by 48 percent and 60 percent of patients with TIL 100mg and by 52 percent and 65 percent of patients with TIL 200mg, respectively. In contrast, 54 percent and 58 percent of patients achieved a PASI 90 response with TIL 100 and 200mg, respectively.

Conclusion: At Weeks 12 and 28, 6 to 10 percent more patients had a PASI score 2.0 or less than had achieved a PASI 90 response, which required a PASI score 1.8 or less for half of the patients based on median baseline PASI score. This suggests that absolute PASI scores might provide a more clinically meaningful measure of residual disease than PASI 90 response rates.

Long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion

Presenters: Yamauchi PS¹, Weiss JS², Lin T³, Pillai R⁴

Affiliations: ¹Clinical Science Institute, Santa Monica, CA; ²Gwinnett Clinical Research Center, Inc., Snellville, GA; ³Ortho Dermatologics, Bridgewater, NJ; ⁴Dow Pharmaceutical Sciences Inc., Petaluma, CA

Background/Objective: Psoriasis is an immune-mediated disease, often chronic with frequent remissions and exacerbations. Patients often stop, restart, or switch therapy. Adherence to topical therapy is generally poor in the majority of the patients, although it is seen to improve with simple regimens and once-a-day therapy. Data on maintenance of efficacy posttreatment are sparse. The objective was to evaluate the maintenance of treatment success following cessation of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe psoriasis.

Methods: This was a one-year multicenter, open-label study in 555 subjects (mean age 51.9 years) with moderate-to-severe plaque psoriasis treated with HP/TAZ lotion. Patients were treated with HP/TAZ lotion once-daily for eight weeks and then as needed; treatment success defined as an Investigator Global Assessment (IGA) score of 0 or 1 (“Clear” or “Almost Clear”). Patients who did not reach treatment success at Week 8 were treated for four additional weeks; otherwise they received no further treatment. All patients were evaluated at Week 12. Those demonstrating at least a one-grade improvement in baseline IGA were subsequently managed in four-week cycles, either treated with HP/TAZ lotion once daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success, with a maximum continuous exposure of 24 weeks.

Results: Overall, 318 patients (57.3%) achieved treatment success at some point during the study; the majority (54.4%, n=173) within the first eight weeks. In many, treatment success was more rapid, being achieved within the first two and four weeks in 12.6 percent and 37.4 percent of patients respectively. Of those patients who stopped therapy after achieving treatment success, 6.6 percent (n=15) did not require any retreatment, 28.3 percent did not require retreatment for at least two months, and the majority (55.3%) did not require retreatment for at least one month. These data are consistent with those reported in the earlier studies with HP/TAZ lotion, where 55 percent of patients who were successes in treatment remained so at the end of the four-week posttreatment follow-up. A limitation was that it was an open-label study.

Conclusion: HP/TAZ lotion provides rapid and sustained treatment success in patients with moderate-to-severe psoriasis when followed for one year.

Disclosures: PSY and JSS are advisors to Ortho Dermatologics and investigators with Dow Pharmaceutical Sciences. TL and RP are employees of Bausch Health.

Maintenance of response with guselkumab for up to three years of treatment in the Phase III VOYAGE 1 trial of patients with plaque psoriasis

Presenters: Griffiths CEM¹, Papp KA², Song M³, Randazzo B³, Li S³, Shen YK³, Han C³, Blauvelt A⁴

Affiliations: ¹Dermatology Centre, University of Manchester, Manchester, United Kingdom; ²K. Papp Clinical Research and Probity Research Inc, Waterloo, Ontario, Canada; ³Janssen Research & Development, LLC, Spring House, PA; ⁴Oregon Medical Research Center, Portland, OR

Background/Objective: Guselkumab (GUS) is a fully human monoclonal antibody that binds and blocks IL-23. VOYAGE 1 is a Phase III, double-blind, placebo- and active comparator-controlled trial that showed significantly higher proportions of patients with moderate-to-severe plaque psoriasis achieving several outcome measures, including Psoriasis Area and Severity Index (PASI) 90 response and Investigator Global Assessment (IGA) 0/1 scores with GUS versus placebo (PBO) at Week 16 and GUS versus adalimumab (ADA) at Week 24. Study results up to three years of continuous treatment with GUS were examined.

Methods: Patients were randomized to GUS 100mg at Weeks 0, 4, and 12, then every eight weeks (Q8WK); PBO at Weeks 0, 4, and 12 followed by GUS 100mg at Weeks 16 and 20 then Q8WK; or ADA 80mg at Week 0, 40mg at Week 1, then 40mg Q2Wk through Week 47. Starting at Week 52, all patients received open-label GUS 100mg Q8WK through Week 156. Efficacy was assessed using prespecified treatment failure rules starting at Week 52 (patients were considered nonresponders after discontinuing due to lack of efficacy, worsening of psoriasis, or use of a prohibited treatment). Data for patients randomized to GUS and for those originally randomized to PBO and then switched to GUS at Week 16 were combined (GUS group).

Results: In total, 837 patients were randomized at baseline. The proportions of patients in the GUS group who achieved designated clinical responses at Weeks 100 and 156, respectively were PASI 90, 82.1 percent (n=448), 82.8 percent (n=431); PASI 100, 51.1 percent (n=448), 50.8 percent (n=431); IGA 0/1, 83.3 percent (n=448), 82.1 percent (n=429); IGA 0, 55.6 percent (n=448), 53.1 percent (n=429); Dermatology Life Quality Index (DLQI) 0/1, 75.2 percent (n=436), 74.7 percent (n=411); Psoriasis Symptoms and Signs Diary (PSSD) symptom score 0, 40.2 percent (n=343), 40.4 percent (n=319); and PSSD sign score 0, 32.9 percent (n=343), 29.2 percent (n=319). No additional safety signals were identified.

Conclusion: High levels of response were stably maintained through up to three years of continuous GUS treatment in patients with moderate-to-severe psoriasis; treatment with GUS was well-tolerated.

Disclosures: CEMG, KAP, and AB are investigators for Janssen Research & Development, LLC. MS, BR, SL, YKS, CH are employees of Janssen Research & Development, LLC.

No increased risk of liver dysfunction from tildrakizumab treatment: post-hoc analyses of the tildrakizumab psoriasis clinical program

Presenters: Lebwohl MG,¹ West DT,² Mendelsohn AM,³ Rozzo SJ,³ Girolomoni G⁴

Affiliations: ¹Department of Dermatology, Mount Sinai Hospital, New York, NY; ²Advanced Dermatology and Cosmetic Surgery, Phoenix, AZ; ³Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁴Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy

Background/Objective: Tildrakizumab (TIL) is a high-affinity, humanized, immunoglobulin G1-kappa, anti-interleukin-23p19 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. We evaluated adverse events related to liver function in the psoriasis clinical development program for TIL.

Methods: This post-hoc analysis included patients with moderate-to-severe chronic plaque psoriasis in a Phase IIb (P05495 [NCT01225731]) and two Phase III trials (reSURFACE 1 [NCT01722331] and 2 [NCT01729754]). In P05495, patients were randomized (1:1:2:2:2) to placebo or TIL 5mg, 25mg, 100mg, or 200mg. In reSURFACE 1 and 2, patients were randomized (1:2:2) to placebo or TIL 100mg or 200mg; reSURFACE 2 had an additional etanercept 50mg arm (1:2:2:2). Patients were treated at Weeks 0 and 4, and then every 12 weeks, and followed for up to Week 52 (P05495 and reSURFACE 2) or Week 64 (reSURFACE 1). The primary safety population included all subjects as treated (1 dose or more of study treatment). We aimed to identify serious liver function test (LFT) findings and evidence of drug-induced liver injury in patients receiving TIL 100mg or 200mg using pooled safety data from the base studies (P05495, n=355; reSURFACE 1, n=771; reSURFACE 2, n=1,090). LFT events of clinical interest were defined as elevated aspartate or alanine transaminase (AST or ALT) levels three or greater times the upper limit of normal (ULN) and elevated total bilirubin levels two or greater times the ULN combined with alkaline phosphatase levels less than two times the ULN.

Results: Data from Year 1 of the extension study are also provided. Placebo-controlled period (Week 0–12/16): two patients (0.6%) in the placebo group and one (0.1%) in the TIL 200mg group discontinued due to elevated LFTs. Base study periods (Week 0–52/64): the numbers of patients (patients with events/100 patient-years) who discontinued due to elevated LFT results were similar in placebo (2 [0.91]) and TIL (4 [0.21]) groups. Two patients had elevated LFT events of clinical interest: the event in one (TIL 200mg, reSURFACE 1) was deemed related to chronic ethanol exposure; the second (etanercept 50mg) had a medical history of increased AST and ALT levels. In the extension period, no patients met the criteria for elevated LFT events of clinical interest. There were no cases of hepatitis B or C activation.

Conclusion: Patients receiving TIL had low rates of increased liver function or drug-induced liver injury, similar to patients receiving placebo or etanercept.

An open-label, observational study evaluating calcipotriene/betamethasone dipropionate foam in psoriasis patients being treated with biologic agents

Presenters: Bagel J, Zapata J, Nelson E, Keegan B

Affiliations: Psoriasis Treatment Center of Central New Jersey; East Windsor, NJ

Background/Objective: Patients receiving biologic therapy for psoriasis might benefit from adjunctive therapy with topical agents. The combination topical treatment calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam, was shown to be significantly more effective than calcipotriene or betamethasone aerosol foams alone and had superior efficacy compared to a gel formulation. This study assessed the effectiveness and safety of combining biologic agents and Cal/BD foam for patients with plaque psoriasis.

Methods: Twenty-five adults with chronic plaque-type psoriasis (body surface area [BSA] 5% or less) who were being treated with biologic agents for 24 weeks or longer were enrolled in an open-label, single-arm observational study. All patients received Cal/BD foam, daily (QD) for four weeks, followed by foam treatment twice per week on consecutive days for 12 weeks. The endpoints were assessed at baseline, Week 4, and Week 16 and included Physician Global Assessment (PGA), BSA, PGA x BSA, Dermatology Life Quality Index (DLQI), and the Treatment Satisfaction Questionnaire for Medication (TSQM)-9. Safety evaluations included assessments of local skin reactions and adverse events (AE).

Results: Subjects included 18 men and seven women, with a mean age of 53±11 years. Cal/BD foam treatment was associated with an improvement of every measure of disease activity. At Week 4, PGA improved by 64 percent (2.8±0.8 at baseline vs. 1.0±0.8 at Week 4; P<0.001). Similarly, BSA improved by 59 percent (2.9±1.2 at baseline vs. 1.2±1.3 at Week 4; P<0.001), and PGA x BSA improved by 78 percent (8.6±4.9 at baseline vs. 1.9±2.6 at Week 4; P<0.001). Notably, at baseline, only three subjects (12%) met treat-to-target criteria (BSA 1 or less), compared to 19 subjects (76%) at Week 4. The corresponding numbers for PGA 1 or less were one (4%) at baseline versus 19 (76%) at Week 4. In addition, subjects experienced a 52-percent improvement in DLQI at Week 4 (P=0.011). Treatment satisfaction at Week 4 was high, with a mean TSQM-9 satisfaction score of 76. Adverse events up to Week 4 were experienced by four subjects and included headache, pruritus, melasma, and a broken toe, which were mild in severity and were deemed unrelated to treatment.

Conclusion: Topical therapy with Cal/BD foam was associated with an improvement of every measure of disease activity in subjects being treated with biologics. Treat-to-target goals were achieved by three of four patients at Week 4.

Funding/Disclosures: This study was sponsored by LEO Pharma Inc. US. Editorial support was provided by p-value communications. JB is an advisor, consultant, investigator, and speaker for AbbVie, Amgen, Celgene, Janssen, Eli Lilly, LEO Pharma, Novartis, and Regeneron. He is an investigator and consultant for Pfizer and an investigator for Valeant, Lycera, UCB, Actelion. He is the Founder of Windsor Dermatology. BK is an investigator and speaker for AbbVie, Janssen, Eli Lilly, Novartis, Pfizer, Actelion, and Valeant and a speaker for Allergan and Promius.

Outcomes of pregnancies from tildrakizumab Phases I to III clinical development program

Presenters: Haycraft K¹, DiRuggiero D², Rozzo SJ³, Mendelsohn AM³, Bhutani T⁴

Affiliations: ¹Riverside Dermatology & Spa, Hannibal, MO; ²Skin Cancer & Cosmetic Dermatology Center, Rome, GA; ³Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁴UCSF Medical Center, San Francisco, CA

Background/Objective: Tildrakizumab (TIL), a high-affinity, humanized, immunoglobulin G1k, anti-interleukin-23p19 monoclonal antibody, has demonstrated efficacy in the treatment of moderate-to-severe chronic plaque psoriasis in three large clinical trials: P05495 (Phase IIb; NCT01225731), reSURFACE 1 (Phase III; NCT01722331), and reSURFACE 2 (Phase III; NCT01729754). Here, we evaluate pregnancy outcomes in women exposed to TIL, specifically cases of spontaneous abortion and congenital anomalies reported during the TIL clinical development program.

Methods: Inclusion criteria included mandatory contraception for participants of both sexes for cases in which at least one partner was a woman of childbearing age. Female patients who were pregnant, intended to become pregnant (within 6 months of completing the trial), or were lactating were excluded from enrollment into the clinical trials. However, the patients who became pregnant during the clinical trials (protocol violators) were categorized, and pregnancy outcome data were evaluated. Data were collected from patients who participated in the following TIL clinical trials: P05661, P05776, and P06306 (in healthy volunteers); P05839 (in patients with Crohn’s disease); and P05382, P009, P05495, reSURFACE 1, and reSURFACE 2 (in patients with psoriasis).

Results: Among 528 patients receiving TIL in clinical trial Phases II to III, a total of 13 pregnancies were reported. These included patients for whom contraception failed (n=5) and patients who did not use contraception (n=8). A total of two pregnancies occurred in the Phase I trials (one in each of the two trials P05661 and P05839), and 11 pregnancies occurred in the Phase IIb/III trials, (i.e., 2 pregnancies in P05495, 5 pregnancies in reSURFACE 1, and 4 pregnancies in reSURFACE 2). The duration of exposure to TIL was variable in these patients, with the longest duration being for a patient who had received 11 doses of TIL 100mg, with the last dose received on Day 784. Medication was immediately stopped after confirmation of pregnancy in these patients. Outcomes were reported for all 13 pregnancies: these included six cases of fetal loss (2 spontaneous abortions [15.4%] and 4 elective abortions [30.8%]) and seven full-term live births with no identifiable congenital anomalies (53.8%). In summary, although contraception in female patients of childbearing age was mandatory prior to initiation of TIL therapy, some pregnancies occurred during the TIL clinical development program as protocol violations. The rate of spontaneous abortion (15.4%) was similar to that seen in the general population (12–15%).

Conclusion: All of the pregnancies that continued to full term resulted in healthy babies with no congenital anomalies.

Funding/Disclosures: The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ; analyses were funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ. Analyses were presented at the DERM 2018 NP/PA Conference, July 19–22, 2018, Las Vegas, NV.

Patient-reported outcomes in subjects with plaque psoriasis treated with tapinarof cream: results from a Phase IIb, randomized, parallel-group study

Presenters: Bhatia N¹, Rubenstein D², Tallman AM³

Affiliations: ¹ Therapeutics Clinical Research, San Diego, CA; ²Dermavant Sciences, Inc., Durham, NC; ³Dermavant Sciences, Inc., New York, NY

Background/Objective: Although multiple options are available for the treatment of plaque psoriasis, there is a need for effective topical therapies that can be used without body surface area (BSA) restrictions or concerns for the duration of treatment. Tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for the treatment of psoriasis and atopic dermatitis.

Methods: This Phase IIb, double-blind, six-arm, vehicle-controlled, randomized study (NCT02564042) assessed the efficacy and safety of tapinarof cream in subjects with plaque psoriasis. Subjects (aged 18–65 years) with chronic stable plaque psoriasis (6 months or longer), BSA involvement between one and 15 percent, and Physician Global Assessment (PGA) score of two or greater at baseline were randomized 1:1:1:1:1:1 to tapinarof cream 0.5% or 1.0% once (QD) or twice daily (BID) or vehicle QD or BID for 12 weeks and followed for four weeks. The previously reported primary endpoint was the proportion of subjects who had a PGA score of zero or a 1 and 2-or-greater-grade improvement from baseline to Week 12. Patient-reported outcomes included change in Psoriasis Symptom Diary (PSD) scores and subject global impression of overall severity of psoriasis symptoms and overall severity of pruritus from baseline to Week 12. Response options ranged from one (very improved) to seven (very worse).

Results: Of 227 subjects randomized, 174 completed the study. Baseline characteristics and demographics were comparable across groups. Overall, 43 to 61 percent of subjects rated their baseline symptoms as moderate, 28 to 44 percent as severe, and 3 to 13 percent as very severe. At Week 12, 82 percent (1.0% BID), 88 percent (1.0% QD), 77 percent (0.5% BID), and 80 percent (0.5% QD) of subjects in the tapinarof cream groups rated change in severity of their psoriasis symptoms as “very/moderately improved” versus 48 percent (BID) and 35 percent (QD) of vehicle-treated subjects. Baseline pruritus scores were similar across all groups. At Week 12, 70 percent (1.0% BID), 76 percent (1.0% QD), 77 percent (0.5% BID) and 73 percent (0.5% QD) of tapinarof cream-treated subjects rated the severity of pruritus as “very improved” or “moderately improved” versus 47 percent (BID) and 35 percent (QD) treated with the vehicle. Reduction in mean weekly PSD scores was higher in the tapinarof cream groups than in the vehicle groups. Moreover, the nine items with the highest severity at baseline improved more for subjects treated with tapinarof cream than those treated with the vehicle. By Week 12, scores had reduced more in the tapinarof cream groups than in the vehicle groups. Overall, 56 percent of subjects in the tapinarof cream groups and 25 percent in the vehicle groups experienced treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. Most common TEAEs (5% or greater) were folliculitis (9%) and contact dermatitis (5%).

Conclusion: Subjects treated with tapinarof cream reported improvements in symptoms, including pruritus from psoriasis, after 12 weeks versus the vehicle. Overall, tapinarof cream was well tolerated.

Funding/dislcosures: Not provided

Physician Global Assessment and body surface area composite tool response in patients with plaque psoriasis after 16 and 48 weeks of certolizumab pegol treatment

Presenters: Merola JF¹, Reich K², Boehnlein M³, Peterson L⁴, Gottlieb AB⁵

Affiliations: ¹Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; ²SCIderm Research Institute, Hamburg, and Dermatologikum Berlin, Germany; ³UCB Pharma, Monheim, Germany; ⁴UCB Pharma, Raleigh, NC; ⁵Department of Dermatology, Icahn School of Medicine at Mt Sinai, New York, NY

Background/Objective: In Phase III trials, treatment with certolizumab pegol (CZP), an Fc-free PEGylated anti-tumor necrosis factor (TNF) biologic, resulted in improvements in patients with plaque psoriasis (PSO), assessed using the Psoriasis Area Severity Index (PASI). The Physician Global Assessment (PGA) and body surface area (BSA) composite tool (PGAxBSA) has previously been shown to be a reliable indicator of disease activity in PSO. The aim of this study was to assess PGAxBSA response in patients with PSO after 16 and 48 weeks of CZP treatment.

Methods: Data were pooled from CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272), ongoing Phase III trials evaluating CZP in adults with PSO of six months or longer (baseline PASI 12 or greater, 10% or greater affected BSA, and PGA 3 or greater on a 5-point scale). At baseline, patients were randomized 2:2:1 to CZP 400mg every two weeks (Q2W), CZP 200mg Q2W (400mg loading dose at Weeks 0, 2, and 4), or placebo. CZP-randomized patients who achieved a 50-percent improvement from baseline in PASI (PASI50) at Week 16 continued the same CZP dose to Week 48; Week 16 PASI50 nonresponders entered an escape arm and are not included in Week 48 analysis. PASI50 nonresponders at Weeks 32, 40, and 48 were withdrawn. This post-hoc analysis evaluates PGAxBSA at Week 16 in patients randomized to CZP 400mg Q2W, 200mg Q2W or placebo at baseline, and Week 48 PGAxBSA in patients who remained on CZP 400mg Q2W or 200mg Q2W through to Week 48. In addition, we present the proportions who achieved a PGAxBSA75 response (75% improvement from baseline in PGAxBSA). Observed data with no imputation are presented.

Results: At Week 0, 461 patients were randomized to placebo (n=100), CZP 400mg Q2W (n=175), or CZP 200mg Q2W (n=186). Mean (standard deviation [SD]) baseline PGAxBSA scores were 77.3 (51.4), 80.0 (58.1) and 80.0 (58.5), respectively. At Week 16, the mean (SD) change from baseline in PGAxBSA score was -12.4 (40.3, n=91) in placebo patients, -63.9 (47.6, n=169) in CZP 400mg Q2W patients, and -64.0 (55.8, n=175) in CZP 200mg Q2W patients, with mean reductions of 11.4 percent, 82.2 percent and 80.0 percent from baseline, respectively. At Week 16, 131 of 169 (77.5%) CZP 400mg Q2W patients and 137 of 175 (78.3%) CZP 200mg Q2W patients achieved PGAxBSA75. Among patients remaining in the trial at Week 48, mean PGAxBSA scores were further improved. In CZP 400mg Q2W patients, the mean (SD) change in PGAxBSA score was -75.0 (50.4, n=130) at Week 48, and in CZP 200mg Q2W patients it was -72.0 (52.6, n=134), a 95.7-percent and 93.0-percent mean reduction, respectively. At Week 48, 128 of 130 (98.5%) CZP 400mg Q2W and 124 of 134 (92.5%) CZP 200mg Q2W patients achieved PGAxBSA75.

Conclusion: Patients with moderate-to-severe PSO showed an 80-percent improvement from baseline in PGAxBSA after 16 weeks of CZP treatment, with mean scores reduced by more than 90 percent from baseline in those remaining in the study to Week 48. PGAxBSA75 was achieved by more than three-quarters of patients at Week 16, and more than 90 percent of patients at Week 48.

Rapid and effective itch relief using calcipotriol plus betamethasone dipropionate foam in patients with psoriasis

Presenters: Jalili A¹, Lebwohl M², Stein Gold L³, Andersen SB⁴, Jensen KL⁴, Thaçi D⁵

Affiliations: ¹Department of Dermatology, Bürgenstock Medical Center, Obbürgen, Switzerland; ²Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; ³Henry Ford Health System, Detroit, MI; ⁴LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark; ⁵Comprehensive Center for Inflammation Medicine, University of Luebeck, Luebeck, Germany

Background/Objective: Itch is common in psoriasis, regardless of disease severity, and is bothersome to many patients, adversely affecting health-related quality of life (HRQoL) and sleep. Topical fixed-dose combination calcipotriol 50ug/g plus betamethasone dipropionate 0.5mg/g cutaneous foam (Cal/BD foam) has demonstrated superior efficacy and favorable tolerability versus Cal or BD alone and versus Cal/BD in gel and ointment formulations in patients with psoriasis. Recently, Cal/BD foam demonstrated good itch relief, comparable to BD foam alone and superior to Cal foam alone. Steroid monotherapy is perceived as the gold standard in itch relief. This pooled analysis evaluated the efficacy of Cal/BD foam on itch and itch-related sleep loss, as well as Dermatology Life Quality Index (DLQI), and timing relative to effect on visible symptoms, versus foam vehicle (FV), through four weeks of treatment.

Methods: Data from three Phase II/III trials (NCT01536886, NCT01866163, NCT02132936) of Cal/BD foam versus FV and active comparators in patients with psoriasis aged 18 years or older with mild-to-severe disease were pooled. For itch-related analyses, only patients with baseline (BL) itch Visual Analog Scale (VAS) greater than 40 were analyzed. For endpoints at Days 3 and 5, only Phase III studies provided patient data. Efficacy endpoints included proportion of patients achieving itch reduction greater than 40 (according to VAS, range 1–100) or 70-percent-or-greater improvement in itch/itch-related sleep loss at Day 3, Day 5, Weeks 1, 2, and 4, or 75-percent improvement in the (excluding head) modified Psoriasis Area Severity Index (mPASI75) from BL at Weeks 1, 2, and 4.

Results: Overall, 837 patients were included in the pooled analysis; 37 patients had BL itch VAS=0 (mean mPASI±SD: 5.76±3.06) and were subsequently excluded (Cal/BD foam, n=610; FV, n=190). Of that, 776 patients (97.0%) had data available at Week 4; there were no systematic reasons for discontinuation. Additionally, 484 had BL itch VAS greater than 40 (mean mPASI±SD: 7.83±5.32). We found no correlation between itch VAS score and mPASI at BL (R²=0.021). In patients with a BL itch VAS greater than 40, the proportion of patients achieving itch VAS reduction greater than 40 increased through four weeks with active treatment versus FV (Cal/BD foam: Day 3: 41.3% [p=0.05], Day 5: 57.5% [p=0.005], Week 1: 60.1%, Week 2: 70.1%, Week 4: 83.0% [p<0.001]; FV: Day 3: 29.2%, Day 5: 40.2%, Week 1: 35.5%, Week 2: 42.5%, Week 4: 45.8%). In patients with BL itch VAS greater than 40, 34.2 percent of Cal/BD-foam-treated patients achieved a 70-percent-or-greater improvement in itch (Itch70) at Day 3, versus 22.5 percent of patients receiving FV (p<0.05); the proportion of patients achieving Itch70 continued to improve through four weeks with active treatment (Cal/BD foam: Day 5: 51.2%, Week 1: 54.4%, Week 2: 68.9%, Week 4: 79.3%; FV: Day 5: 28.7%, Week 1: 26.5%, Week 2: 36.7%, Week 4: 38.1; p<0.001). In patients with BL itch VAS greater than 40/sleep loss greater than 20, improvements in itch-related sleep loss occurred at Week 1 and continued to improve through four weeks. These improvements occurred before significant improvements in mPASI75 were observed. Data for DLQI are provided for Phase III data only (Cal/BD foam: n=178; FV: n=52); at baseline, all patients had a DLQI score greater than five. An improvement in DLQI was observed in both treatment groups: 44.2 percent of Cal/BD foam-treated patients and 18.3 percent of FV-treated patients achieved DLQI 0/1 at Week 4. Significant differences between Cal/BD foam- versus FV-treated patients were observed in those with BL DLQI greater than 10 (n=172 vs. n=50) who achieved a DLQI score of one or less (25.0 vs. 4.0%; p=0.001) and DLQI 0 (17.4 vs. 2.0%; p=0.006) at Week 4.

Conclusion: Cal/BD foam offers more rapid and effective relief from itch than FV; itch reduction is associated with significant improvements in sleep and DLQI. Cal/BD foam has a direct impact on itch relief observed before improvements in visible disease severity (mPASI).

Disclosures: AJ has been a consultant and advisor and/or received speaking fees and/or grants and/or served as an investigator in clinical trials for the following companies: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, GSK, LEO Pharma Janssen-Cilag, MSD, Novartis and Sanofi. ML is an employee of Mount Sinai which receives research funds from: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, MedImmune/Astra Zeneca, Novartis, Pfizer, Valeant and ViDac; is a consultant for Allergan, Aqua, Boehringer-Ingelheim, LEO pharma, Promius, and Menlo. LSG has been an investigator and/or advisor for LEO Pharma., Celgene, Janssen, Novartis, Pfizer, Taro. DT has been a consultant and advisor and/or received speaking fees and/or grants and/or served as an investigator in clinical trials for the following companies: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, BMS, Celgene, Dignity, Eli Lilly, Forward Pharma, Galapagos, GSK, Leo Pharma, Janssen-Cilag, Maruho, Mitsubishi Pharma, MSD, Mundipharma, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and Xenoport. SA and KJ are employees of LEO Pharma A/S.

Response to mirikizumab at Week 52 among patients who did not achieve a PASI 90 response at Week 16

Presenters: Papp K¹, Maari C², Rich P³, Klekotka P⁴, Li J⁴, Tuttle J⁴, Patel D⁴, Arora V⁴, Reich K⁵

Affiliations: ¹K. Papp Clinical Research, Waterloo, Ontario, Canada; Probity Medical Research, Waterloo; ²Innovaderm Research, Montreal, Quebec, Canada; ³Oregon Dermatology & Research Center; ⁴Eli Lilly & Company, Indianapolis, IN; ⁵SCIderm Research Institute, Hamburg, and Dermatologikum Berlin, Germany.

Background/Objective: Interleukin-23 (IL-23) is believed to be critical to the pathogenesis of psoriasis. Inhibition of the IL-23/T-helper (Th) 17 pathway leads to high levels of skin clearance in patients with psoriasis. Mirikizumab (LY3074828) is a humanized monoclonal antibody directed against p19 subunit of IL-23. The objective of the study was to present 52-week efficacy and safety results among patients with moderate-to-severe plaque psoriasis who did not achieve at least 90-percent improvement in the Psoriasis Area and Severity Index (PASI 90) at Week 16 in a Phase II (AMAF, NCT02899988), multicenter, randomized, double-blind, placebo-controlled trial.

Methods: The primary objective was to evaluate superiority of mirikizumab to placebo in achieving PASI 90 response at Week 16. The secondary objectives included comparison between mirikizumab and placebo for: safety and tolerability; PASI 100, PASI 90, and PASI 75 response at Week 16; PASI 100, PASI 90, and PASI 75 response at Week 52.

Results: At Week 16, 29.4 percent (n=15), 58.8 percent (n=30), and 66.7 percent (n=34) of patients treated with mirikizumab 30mg, 100mg, and 300mg, respectively, had a PASI 90 response compared to zero percent in placebo-treated patients. During Weeks 16 to 52 of this study, among patients who did not achieve PASI 90 at Week 16, the most common (5% or greater) treatment-emergent adverse events (AEs) included nasopharyngitis (n=25; 20.8%), upper respiratory tract infection (n=12; 10.0%), urinary tract infection (n=6; 5.0%), arthralgia (n=8; 6.7%), back pain (n=6; 5.0%), headache (n=6; 5.0%), injection-site pain (n=7; 5.8%), and hypertension (n=6; 5.0%). Four (3.3%) patients experienced serious AEs (SAEs) and six (5.0%) patients discontinued the study due to AEs in this group of patients during Weeks 16 to 52.

Conclusion: Among patients who did not achieve a PASI 90 response after 16 weeks of treatment, high percentages of patients achieved PASI 90 at Week 52 with 300mg once every eight weeks (Q8W), regardless of treatment during the first 16 weeks of the study. The safety profile at Week 52 was consistent with that of Week 16 and other studies on anti-IL-23p19 monoclonal antibodies.

Funding/Disclosures: KP has received grant/research support: AbbVie, Allergan, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dermira, Eli Lilly and Company, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Takeda. CM has been an advisory board member, investigator and/or speaker for AbbVie, Amgen, Celgene, Eli Lilly and Company, Galderma, Leo Pharma, Merck, Novartis, and Tribute. PR has received grant/research support: AbbVie, Allergan, AnacorPharmaceuticals, Boehringer Ingelheim, CassiopeaSpA, Dermira, Eli Lilly and Company, Galderma Laboratories, Janssen-Ortho, KadmonCorporation, Leo Pharma, Merck, Moberg Derma, Novartis, Pfizer, Ranbaxy Laboratories Limited, Sandoz, Viamet, Cellceutix, and Cutanea. KR served as advisor and/or paid speaker for AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Takeda, UCB Pharma, and Xenoport. PK, JL, JT, and DP are current employees and shareholders of Eli Lilly and Company. We acknowledge Ananya Biswas, from Eli Lilly and Company, who provided medical writing assistance. This study was sponsored by Eli Lilly and Company.

Safety and efficacy of a fixed combination halobetasol and tazarotene lotion in the treatment of moderate-to-severe plaque ssoriasis: subgroup analysis

Presenters: Stein Gold L¹, Lain E², Bagel J³, Lin T⁷, Martin G⁸, Pillai R⁸

Affiliations: ¹Henry Ford Hospital, Detroit, MI; ²Private Practice, Austin, TX; ³Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; ⁴Ortho Dermatologics, Bridgewater, NJ; ⁵Dow Pharmaceutical Sciences Inc., Petaluma, CA

Background/Objective: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment, but safety concerns might limit use. Combination with tazarotene might optimize efficacy and minimize safety and tolerability concerns. The objective was to investigate safety and efficacy of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis.

Methods: The study included two multicenter, randomized, double-blind, vehicle-controlled Phase III trials (N=418). Subjects randomized (2:1) to HP/TAZ lotion or vehicle once-daily for four weeks with a four-week follow-up. Primary efficacy assessment was measured based on treatment success (at least a two-grade improvement from baseline in IGA score and ”clear” or “almost clear”). Safety and treatment-emergent AEs were evaluated throughout. Differences in treatment success and safety were evaluated in a number of subpopulations.

Results: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as Week 2 (p=0.002). By Week 8, 40.6 percent of subjects were treatment successes compared to 9.9 percent on the vehicle (p<0.001). HP/TAZ lotion appeared more efficacious in subjects who were women, younger, and with moderate psoriasis. By Week 8, 41.6 percent of subjects with moderate disease (compared to 35.0% severe); 44.6 percent of female subjects (compared to 38.4% male); and 43.4 percent of subjects younger than 51 years (compared to 37.9% 51 years or older) were treatment successes. Ethnicity did not appear to influence efficacy. Treatment-related adverse events (AEs) were more common in female subjects (23.2% compared to 18.7%), although they tended to be milder.

Conclusion: HP/TAZ lotion provides good efficacy and tolerability overall, with greater efficacy in patients who are younger women with moderate psoriasis.

Safety and efficacy of halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis: a pooled analysis of two Phase III studies

Presenters: Sugarman JL¹, Weiss J², Tanghetti EA³, Soung J⁴, Yamauchi PS⁵, Lin T⁶, Harris S⁷, Martin G⁸, Pillai R⁸

Affiliations: ¹University of California, San Francisco, CA; ²Gwinnett Dermatology, PC, and Gwinnett Clinical Research Center, Inc, Snellville, GA; ³Center for Dermatology and Laser Surgery, Sacramento, CA; ⁴Southern California Dermatology, Santa Ana, CA; ⁵David Geffen School of Medicine at UCLA, Los Angeles, CA; ⁶Ortho Dermatologics, Bridgewater, NJ; ⁷Bausch Health, Bridgewater, NJ. ⁸Dow Pharmaceutical Sciences Inc., Petaluma, CA

Background/Objective: Clinical trials have studied twice-daily dosing of topical corticosteroids (TCS); safety concerns and labeling limit consecutive use to 2 to 4 weeks. The objective was to investigate safety and efficacy of once-daily halobetasol propionate (HP) 0.01% lotion in moderate-to-severe plaque psoriasis.

Methods: The study included two multicenter, randomized, double-blind, vehicle-controlled Phase III trials (N=430). Patients were randomized (2:1) to HP lotion or vehicle once-daily for eight weeks with a four-week follow-up. Primary efficacy assessment was based on treatment success (at least a two-grade improvement from baseline in Investigator Global Assessment [IGA] score and “clear” or “almost clear”). Additional assessments included improvement in psoriasis signs and symptoms, body surface area (BSA) and a composite score of IGAxBSA. Patients achieving a 50-percent reduction in IGAxBSA (IGAxBSA-50) were considered to have a clinically meaningful outcome. Safety and treatment-emergent adverse events (AEs) evaluated throughout.

Results: HP lotion demonstrated statistically significant superiority over the vehicle as early as Week 2. By Week 8, 37.5 percent of patients were considered treatment successes compared to only 10.0 percent on vehicle (P<0.001). HP lotion was also superior in reducing psoriasis symptoms and BSA involvement. Overall, there was a 49.4-percent reduction in mean IGAxBSA composite score by Week 8, and 56.8 percent of patients achieved IGAxBSA-50, (both P<0.001) versus the vehicle. There were only five treatment-related AEs following use with HP lotion, the most common being application site dermatitis (0.7%). A limitation of the study was that IGAxBSA evaluations were post hoc.

Conclusion: HP 0.01% lotion provides significant efficacy over eight weeks, with good tolerability and safety.

Secukinumab improves GRAPPA-OMERACT core domains of psoriatic arthritis

Presenters: Orbai AM¹, McInnes I², Coates L³, Husni ME⁴, Gladman D⁵, Pricop L⁶, Chambenoit O⁶, Meng X⁶, Mease P⁷

Affiliations: ¹Johns Hopkins University School of Medicine, Baltimore MD; ²University of Glasgow, Glasgow, United Kingdom; ³NDORMS, University of Oxford, Oxford, UK; ⁴Cleveland Clinic, Cleveland, OH; ⁵Toronto Western Research Institute and University of Toronto, Toronto, Ontario, Canada; ⁶Novartis Pharmaceutical Corp, East Hanover, NJ; ⁷Swedish Medical Center and University of Washington, Seattle, WA

Background/Objective: Secukinumab (SEC), a fully human monoclonal antibody that selectively neutralizes IL-17A, has demonstrated efficacy for patients with psoriatic arthritis (PsA) in multiple Phase III clinical trials. To improve and standardize the assessment of outcomes, the PsA core domain set has been updated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and endorsed by Outcome Measures in Rheumatology (OMERACT) in 2016. The updated PsA core domains are: musculoskeletal disease activity (arthritis, enthesitis, dactylitis, and spine symptoms), skin disease activity (psoriasis and nail psoriasis), pain, patient global assessment, physical function, fatigue, health-related quality of life, and systemic inflammation. Here, we report the efficacy of SEC versus placebo (PBO) across individual PsA core domains using pooled data from four Phase III FUTURE studies.

Methods: Patients with active PsA participated in the Phase III clinical trials FUTURE 2, 3, 4, and 5 (N=397, N=414, N=341, and N=996, respectively). Data were pooled into SEC dosed at 150mg (load vs. no load), 300mg, or PBO at the end of the 16-week double-blind period, and efficacy was evaluated according to the updated GRAPPA-OMERACT PsA core domains. Core domains were assessed using multiple instruments, with improvement defined as the percentage of patients achieving 50-percent-or-greater improvement (joints), complete resolution (arthritis, enthesitis, or dactylitis), or minimal clinically important difference in PsA where known and/or least squares mean change from baseline (patient-reported outcomes). Axial data are from MEASURE 2 (not assessed in FUTURE studies).

Results: In total, 2,049 patients were included; 461 received SEC 300mg, 572 received SEC 150mg, 335 received SEC 150mg no load, and 681 received PBO. Baseline demographics and disease characteristics were broadly similar in all treatment groups. SEC demonstrated significant efficacy versus PBO (P<0.05) across GRAPPA-OMERACT PsA core domains in the Phase III clinical trials program using multiple instruments and thresholds to measure improvement. SEC 300mg had the greatest efficacy across domains versus PBO.

Conclusion: SEC improves both the disease manifestations and life impact of PsA as demonstrated using the PsA core domain set.

Funding: This investigation was sponsored by Novartis Pharma AG, Basel, Switzerland. Originally presented at the ACR/ARHP Annual Meeting, Chicago, IL, November 8 to 13, 2018.

Secukinumab provides rapid relief from pain and itch in patients with moderate-to-severe psoriasis: diary data from pooled ERASURE and FIXTURE studies

Presenters: Yosipovitch G¹, Soung J², Weiss J³, Muscianisi E⁴, Meng X⁴, Gilloteau I⁵, Elewski BE⁶

Affiliations: ¹Miami Itch Center at the University of Miami, Leonard M. Miller School of Medicine, Miami, FL; ²Southern California Dermatology, Santa Ana, CA; ³Gwinnett Clinical Research Center, Snellville, GA; ⁴Novartis Pharmaceutical Corp, East Hanover, NJ; ⁵Novartis Pharma AG, Basel, Switzerland; ⁶University of Alabama at Birmingham School of Medicine, Birmingham, AL

Background/Objective: Effective treatments for moderate-to-severe psoriasis should relieve psoriasis-related symptoms (e.g. pain and itch), beyond clearing skin. For many patients, itch is the most bothersome symptom and is closely related to psychosocial wellbeing. Secukinumab (SEC), a fully human monoclonal antibody that selectively neutralizes interleukin 17A, is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.

Methods: Time to pain and itch relief (scale, 0–10) derived from patients’ daily Psoriasis Symptom Diaries (PSDs) during the first 12 weeks of treatment was assessed in ERASURE (NCT01365455) and FIXTURE (NCT01358578), two SEC Phase III trials.

Results: Pooled analysis included 2,042 patients randomized to SEC 150mg (n=572) or 300mg (n=572), placebo (n=572), or etanercept (n=326); 39 percent completed PSDs at baseline and 35 percent at Week 12. Relief from itch (mean score change from baseline) started as early as Week 2 with SEC (150mg, -1.36; 300mg, -1.38) versus placebo (-0.25) and etanercept (-0.69); greater improvements were seen at Week 4 with SEC (150mg, -2.87; 300mg, -3.03) versus placebo (-0.42) and etanercept (-1.86). Relief from pain also started as early as Week 2 with SEC (150mg, -1.48; 300mg, -1.55) versus placebo (-0.07) and etanercept (-0.74); greater improvements were observed at Week 4 with SEC (150mg, -2.65; 300mg, -2.92) vs. placebo (-0.28) and etanercept (-1.81). Improvements in pain were observed at Week 12 with SEC (150mg, -4.02; 300mg, -4.52) versus placebo (-0.16) and etanercept (-3.48). At Week 2, more patients had pain values of zero (no pain) or one (minimal pain) with SEC (150mg, 11.9%; 300mg, 13.9%) versus placebo (5.6%) and etanercept (7.0%). At Week 12, no/minimal pain was observed in 64.6 percent and 72.4 percent of patients receiving SEC 150mg and 300mg, respectively, versus 6.3 percent receiving placebo and 48.0 percent receiving etanercept. Similarly, at Week 2, more patients had itch values of zero or one with SEC (150mg, 2.7%; 300mg, 6.0%) versus 1.4 percent with placebo and 1.6 percent with etanercept. This trend continued to Week 4. By Week 12, no/minimal itch was observed in 57.2 percent and 68.6 percent of patients treated with SEC 150mg and 300mg, respectively, versus 4.2 percent with placebo and 39.8 percent with etanercept.

Conclusion: By Week 4, greater improvements in itch and pain were observed with SEC (150mg, 300mg) versus placebo and etanercept, and were sustained up to Week 12. Relief from itch and pain should be addressed when treating patients.

Funding: This investigation was sponsored by Novartis Pharma AG, Basel, Switzerland. Originally presented at the Fall Clinical Dermatology Conference (FCDC), Las Vegas, NV, October 18 to 21, 2018.

Secukinumab rapidly improves mobility, self-care, and usual activities in patients with psoriasis: pooled analysis from four Phase III trials

Presenters: Feldman SR¹, Gomez B², Meng X², Germino R²

Affiliations: ¹Wake Forest Baptist Medical Center, Winston-Salem, NC; ²Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background/Objective: Beyond skin manifestations, patients with psoriasis experience decreased health-related quality of life due to impaired movement. Secukinumab (SEC) is a fully human monoclonal antibody that selectively neutralizes interleukin 17A and has shown long-lasting efficacy and safety in the treatment of the complete spectrum of psoriasis manifestations. For hypothesis generation, this retrospective pooled analysis assessed the effect of SEC treatment on the mobility, self-care, and usual activities domains of the three-level EuroQol 5-Dimensions (EQ-5D-3L) questionnaire in patients with moderate-to-severe psoriasis.

Methods: This pooled analysis of four Phase III clinical trials (ERASURE, FIXTURE, FEATURE, and JUNCTURE) included patients with moderate-to-severe psoriasis who were randomized to receive placebo or SEC 300mg and who reported problems with mobility, self-care, or usual activities at baseline. Demographics, clinical characteristics, and treatment history were examined at baseline. Percentage of patients reporting problems in EQ-5D-3L mobility, self-care, or usual activities domains were compared at Weeks 4, 8, and 12 between patients receiving placebo and those receiving SEC 300mg.

Results: Among the 282 patients receiving placebo and 309 receiving SEC 300mg, respectively, who reported at least one problem at baseline, 172 and 180 reported problems with mobility, 94 and 99 with self-care, and 214 and 254 with usual activities at baseline. The mean ages of patients receiving placebo and 300mg SEC, respectively, were 45.7 and 44.3 years, 67.4 percent and 64.4 percent were male, with mean times since psoriasis diagnosis of 16.8 and 16.6 years; 30.1 percent and 25.9 percent had concurrent PsA diagnosis and 27.3 percent and 22.7 percent had prior biologic use. The percentage of patients with problems in mobility at Week 4 was lower with SEC 300mg compared to placebo (39.31 vs. 61.45%); similar trends were observed at Weeks 8 (26.40 vs. 51.90%) and 12 (28.57 vs. 53.38%). The percentage of patients with problems in self-care at Week 4 was lower with SEC 300mg compared to placebo (28.57 vs. 59.14%); similar trends were observed at Weeks 8 (20.83 vs. 57.65%) and 12 (12.90 vs. 56.96%). The percentage of patients with problems in usual activities at Week 4 was lower with SEC 300mg compared to placebo (36.21 vs. 68.93%); similar trends were observed at Weeks 8 (25.61 vs. 64.29%) and 12 (17.30 vs. 57.38%). Patients receiving SEC 300mg reported significant improvements in mobility, self-care, and usual activities at Week 12 compared to patients receiving placebo (all P<0.0001).

Conclusion: In this pooled analysis of four Phase III trials of patients with moderate-to-severe psoriasis, treatment with SEC resulted in improvements from baseline through 12 weeks in mobility, self-care, and usual activities compared to placebo. These findings highlight the importance of treating patients with moderate-to-severe psoriasis beyond the achievement of skin clearance to also improve their overall quality of life.

Disclosures: SRF has received consulting, speaking, and/or research support from Novartis, AbbVie, Celgene, Sun Pharma, Janssen, Lilly, and Ortho. BG, XM, and RG are employees of Novartis.

ROSACEA

Combined doxycyclin 40mg modified release capsules plus ivermectin 1% cream therapy for severe papulopustular rosacea

Presenters: Del Rosso J¹, Johnson S², Jackson M³

Affiliations: ¹JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; ²Johnson Dermatology Clinic, Fort Smith, AR; ³University of Louisville, Louisville, KY

Background/Objective: Rosacea is a chronic inflammatory skin disease that is often best managed with combination therapy. There have been a limited number of rigorous controlled studies of combination therapies, despite high interest in such approaches. Doxycycline 40mg modified release (DMR) and ivermectin 1% cream (IVM) are two well-established treatments for rosacea with proven efficacy, tolerability, and safety. DMR and IVM have different and complementary targets in the inflammatory cascade of rosacea, suggesting this would be a potentially effective combination. The objective of our study was to evaluate whether DMR+IVM was more efficacious than IVM alone in treating severe papulopustular rosacea (PPR; Investigator Global Assessment [IGA] 4), and whether there was a better improvement in quality of life with combination versus monotherapy. Additionally, we studied whether combination therapy could increase the percentage of subjects reaching “clear” (IGA 0; 100% reduction of inflammatory lesions plus no erythema) as well as relief of other rosacea-associated symptoms.

Methods: This was a 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study. Subjects aged 18 years or older with severe PPR (IGA 4), including more than 20 to 70 inflammatory lesions on the face, were eligible and were randomized to either DMR+IVM (combination arm) or IVM+placebo. All subjects used Cetaphil Redness Relieving facial wash and Cetaphil Redness Relieving Moisturizer, sun protection factor (SPF) 30. The primary efficacy assessment was percent change in inflammatory lesion count from baseline to Week 12; secondary variables included Clinician’s Erythema Assessment (CEA) and change in stinging/burning and flushing. Adverse events and cutaneous tolerability were recorded.

Results: A total of 273 IGA 4 patients with rosacea participated; 60 percent had severe erythema (CEA 4), 50 percent had moderate to severe stinging/burning, and 40 percent had ocular symptoms. Compared to IVM alone, the combination of DMR+IVM:

Displayed superior efficacy in reduction of inflammatory lesions (-80.29 vs. -72.56%, P=0.032) and IGA score (P=0.032).
Combination therapy had a faster onset of action, with a significant differences over topical alone, as early as Week 4.
Significantly increased the number of subjects achieving IGA 0 (11.9 vs. 5.1%, P=0.043) and 100-percent lesion reduction (17.8 vs. 7.2%, P=0.006) at Week 12.
Both combination and monotherapy treatment arms substantially reduced CEA score, burning/stinging, flushing frequency, Dermatology Life Quality Index (DLQI) and ocular symptoms. The combination of DMR+IVM was well tolerated, there were no increases in GI-related symptoms, and there were no discontinuations of treatment due to related side effects.

Conclusion: Combination therapy with DMR+IVM was shown to be a safe and more efficacious option compared to monotherapy in the treatment of PPR.

Funding/dislcosures: Not provided

Efficacy and safety of FMX103 (1.5% minocycline foam) in the treatment of moderate-to-severe papulopustular rosacea: results from two Phase III randomized, multicenter, double-blind, vehicle-controlled studies

Presenters: Stein Gold L¹, Del Rosso JQ², Bhatia ND³, Hooper D⁴, Nahm W⁵, Stuart I⁶

Affiliations: ¹Henry Ford Health System, Detroit, MI; ²Touro University Nevada, Henderson, NV; ³Therapeutics Clinical Research, San Diego, CA; ⁴Delricht Research, New Orleans, LA; ⁵Scripps Mercy Hospital, San Diego, CA; ⁶Foamix Pharmaceuticals, Inc., Bridgewater, NJ

Background/Objective: To determine the efficacy, safety, and local tolerability of FMX103 1.5% topical minocycline foam used for 12 weeks in the treatment of papulopustular rosacea.

Methods: Two Phase III, randomized, multicenter, double-blind, vehicle-controlled, two-arm studies (Study FX2016-11 and Study FX2016-12) were conducted in subjects of 18 years or older of age with moderate-to-severe papulopustular rosacea. Subjects were randomized 2:1 to either FMX103 or vehicle treatment respectively and applied, or had applied for them, FMX103 foam or vehicle foam once daily to the face for 12 weeks. They were evaluated at baseline and Weeks 2, 4, 8, and 12. Coprimary efficacy endpoints were absolute change from baseline in inflammatory lesion count and the proportion of subjects with treatment success, defined as an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a two-grade improvement from baseline at Week 12. Safety evaluations included adverse events, vital signs, physical examination, laboratory investigations, and local tolerability assessment. Subject global assessment (SGA) and subject satisfaction were assessed by a questionnaire at Week 12.

Results: A total of 1,522 subjects were enrolled in the two studies (Study FX2016-11, n=751; Study FX2016-12, n=771). At baseline, in Study FX2016-11 and FX2016-12, respectively, the mean inflammatory lesion count was 28.5 and 30.0 for the FMX103 treatment groups, and 29.0 and 30.2 for the vehicle treatment groups. Both studies met both coprimary endpoints. There were statistically significant reductions in number of inflammatory lesions from baseline with FMX103 (Study FX2016-11, -17.57 vs. -15.65, P=0.003; Study FX2016-12, -18.54 vs. -14.88; P<0.0001) and significantly higher rates of IGA treatment success versus vehicle (Study FX2016-11, 52.1 vs. 43.0%, P=0.027; Study FX2016-12, 49.1 vs. 39.0%, P=0.008). The most common treatment-emergent adverse event (TEAE) for both studies was upper respiratory tract infection. There were no serious treatment-related TEAEs. Overall, nine subjects across both studies discontinued due to a TEAE (FMX103, seven subjects; vehicle, two subjects).

Conclusion: FMX103 appeared to be effective with a favorable safety profile for the treatment of moderate-to-severe papulopustular rosacea.

Funding/Disclosures: Not provided

SEBORRHEIC KERATOSES

Assessing patient satisfaction with hydrogen peroxide topical solution, 40% (w/w) treatment of seborrheic keratoses on the face, neck, and décolletage: objectives and design of the Phase IV, open-label SK-FAN study

Presenters: DuBois J¹, Grande K², Schnyder J³, Shanler SD³

Affiliations: ¹DermResearch, Inc., Austin, TX; ²The Skin Wellness Center, Knoxville, TN; ³Aclaris Therapeutics, Inc., Wayne, PA

Background/Objective: Seborrheic keratoses (SKs) are benign cutaneous lesions affecting about 84 million individuals in the United States. A proprietary hydrogen peroxide topical solution 40% (w/w) (HP40) is approved by the United States Food and Drug Administration for the treatment of raised SKs. This report describes the methodology of a Phase IV, open-label study designed to assess participant satisfaction following HP40 treatment of SKs located on the face, neck, and décolletage.

Methods: Eligible participants were aged 30 to 75 years with a diagnosis of stable, clinically typical SKs, including two target SKs located on the face and one target SK located on the neck or décolletage. Target SKs had a Physician Lesion Assessment (PLA) of two or greater on a four-point scale (0=clear; 1=near clear; 2=thin [1mm or less]; 3=thick [>1mm]), were 5 to 15mm in diameter, and were treated with HP40 on study Day 1, and Days 15 and 29 if lesions met criteria for treatment. Patient satisfaction was assessed predose (Day 1), 24 hours after the Day 2 dose, one week after Day 15 and 29 dosing, and on Days 85 and 113 (study end) using the Subject Satisfaction Assessment (SSA; 1=not satisfied at all; 2=slightly satisfied; 3=moderately satisfied; 4=satisfied; 5=very satisfied). The primary outcome measure was Question #4 of the SSA, “On a scale of 1–5, rate your level of satisfaction with the appearance of your skin treated with [HP40].” The secondary outcome measure was Question #3 of the SSA, “On a scale of 1–5, rate your level of satisfaction of your treatment experience.” Question #10 and its four constructs of confidence, attractiveness, embarrassment, and comfort with being photographed were tertiary outcome measures.

Results: Exploratory outcome measures were predose and postdose SSA ratings. Additional analyses were correlations between PLA and SSA scores, and predictors of treatment satisfaction (i.e., participant characteristics). A total of 30 participants were enrolled at three United States centers. Data analyses are currently ongoing with results expected in early 2019.

Funding/Disclosures: Not provided

Safety of hydrogen peroxide topical solution 40% (w/w) in patients with skin of color and seborrheic keratoses: pooled analysis of two Phase III, randomized, double-blind, vehicle-controlled, parallel-group studies

Presenters: Hren C¹, Tschen E², Jones TM³, Bradshaw M⁴, Schnyder J⁵, Shanler SD⁵

Affiliations: ¹Cary Dermatology Center, Cary, NC; ²Academic Dermatology Associates, Albuquerque, NM; ³J&S Studies, Inc., College Station, TX; ⁴GCP-MB, LLC, Asbury Park, NJ; ⁵Aclaris Therapeutics, Inc., Wayne, PA

Background/Objective: A hydrogen peroxide topical solution, 40% (w/w) (HP40) is approved by the United States Food and Drug Administration for the treatment of raised seborrheic keratoses (SKs). Limited information is available regarding HP40 treatment in patients with skin of color. We evaluated HP40 safety in a subset of patients with SKs and Fitzpatrick skin type of IV or greater.

Methods: In two Phase III, multicenter, randomized, double-blind, vehicle-controlled studies (NCT02667236, NCT02667275), eligible adults with four target SKs (1 or more on the face and 1 or more on the trunk or extremities) were randomized to HP40 or vehicle. Safety assessments were treatment-emergent adverse events (TEAEs) and local skin reactions (LSRs). A post-hoc, pooled analysis evaluated HP40 safety in patients with a Fitzpatrick skin Type IV, V, or VI who participated in the two vehicle-controlled Phase III trials.

Results: A total of 97 patients with Fitzpatrick skin Types IV, V, or VI were included in the pooled analysis (HP40, n=39; vehicle, n=58). Baseline demographics were similar between groups (mean age, 67.3 years; female, 49.5%). Incidences of LSRs were similar between groups and most were mild. By Visit 8 (Day 106, end of study), no HP40-treated patients reported an LSR of pruritus or stinging, and no investigator observed atrophy, edema, erosion, scarring, ulceration, or vesicles. At Visit 8, investigator-observed LSRs among HP40-treated target lesions were mild (crusting, 3.8%; erythema, 3.2%; hyperpigmentation, 11.5%; hypopigmentation, 2.6%; scaling, 3.8%) or moderate (crusting, 0.6%; hyperpigmentation, 2.6%). No severe LSRs were reported at Visit 8. Only one TEAE was reported (post-procedural complication in the HP40 group).

Conclusion: HP40 treatment was safe and well tolerated in patients with skin of color and SKs on the face, extremities, and trunk. At the final study visit (Day 106), no LSRs were severe, and all except crusting and hyperpigmentation were mild.

Funding/Disclosures: Not provided.