Selected Abstracts from MauiDerm 2021 for Dermatologists

J Clin Aesthet Dermatol. 2021;14(5 Suppl 1):S8–S30. © µ µ ?

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

Click the cover to access the digital version of this supplement

Dear Colleagues:

The 2021 edition of the Maui Derm for Dermatologists meeting had a variety of clinical and scientific data presented, but not just at the podium. A wide range of clinically relevant material was also presented in poster format. For those of you who were unable to participate in the meeting or were not able to attend the poster sessions, we have compiled abstracts from a select group of research posters presented during the 2021 meeting. It is my hope that you will find the highlighted research informative and thought provoking.

For an alphabetical index organized by poster presenter names, please see page 31 of this supplement.

With aloha,

George Martin, MD

MauiDerm 2021 Program Director; Guest Editor, The Journal of Clinical and Aesthetic Dermatology

Funding for this supplement was provided by Amgen.

CONTENT

ACNE

A prospective, multicenter, randomized, double-blind, vehicle-controlled Phase II study to evaluate the safety and efficacy of a combination of 3% minocycline and 0.3% adapalene topical foam formulation for the treatment of moderate-to-severe acne
Efficacy and safety of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% (E-BPO/E-ATRA) cream in acne vulgaris: Results from two randomized, controlled pivotal clinical trials
Long-term safety and tolerability of sarecycline for the treatment of acne vulgaris: Results from a Phase III, multicenter, open-label study and a Phase I phototoxicity study
Reduced blood-brain barrier penetration of sarecycline relative to minocycline in rats corresponds with lipophilicity

ACTINIC KERATOSIS

Favorable safety profile of tirbanibulin ointment 1% for actinic keratosis: Pooled results from two Phase III studies

ALOPECIA

Efficacy and safety of baricitinib in the treatment of patients with severe or very severe alopecia areata: Phase II portion of BRAVE-AA1 randomized controlled trial

ATOPIC DERMATITIS

Clinical tailoring of baricitinib 2mg in atopic dermatitis: Baseline body surface area and rapid onset of action identifies response at Week 16
Conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: Pooled results from five clinical trials
Dupilumab treatment provides improvements in signs of AD at Week 100 in adult patients with moderate-to-severe AD who did not achieve ? 75-percent reduction in Eczema Area and Severity Index at Week 16
Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Pooled analysis of two Phase III, randomized, double-blind studies
Laboratory safety of dupilumab in adolescent patients with atopic dermatitis: 52-week laboratory safety findings from an open-label study (LIBERTY AD PED-OLE)
Laboratory safety of dupilumab in pediatric patients aged 6 to 12 years with severe atopic dermatitis: Results from a Phase III trial (LIBERTY AD PEDS)
Onset of symptom relief reported in daily diaries in patients with atopic dermatitis treated with baricitinib in a US clinical trial
Rapid itch improvement in children with severe atopic dermatitis treated with dupilumab: A Phase III subset analysis
Results from ADVISE: A randomized, double-blind, placebo-controlled Phase II study of etrasimod, an oral, selective, sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis
Risk of venous thromboembolism among patients with atopic dermatitis: A cohort study in a US administrative claims database
The safety and efficacy of roflumilast cream 0.15% and 0.05% in atopic dermatitis: Phase II proof-of-concept study
Tralokinumab provides progressive improvements beyond Week 16 in patients with atopic dermatitis with an initial partial response

CELLULITIS

Incidence and outcomes of imaging for cellulitis in hospitalized patients with active intravenous drug use

CUTANEOUS ONCOLOGY

Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): A case series

MISCELLANEOUS

Approach to hospitalized patients with fever and rash: A retrospective analysis of clinicopathologic features
Phase II safety and efficacy of VP-102, a drug-device combination product containing cantharidin (0.7% w/v), for the treatment of external genital warts (CARE-1)
Plasma cell vulvitis: A systematic review
Topical treatments for pediatric toenail onychomycosis: Overview of efficacy in three clinical trials
Variations in systemic disease and cardiovascular involvement in patients presenting with cutaneous sarcoid between racial groups

MOLLUSCUM CONTAGIOSUM

The hidden impact of molluscum contagiosum: Survey of caregivers’ experiences with diagnosis and management

PRURITUS

A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine ER tablets for uremic pruritus
Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: Results of a Phase II randomized controlled trial with an open-label extension phase
The role of kappa and mu opioid receptors in pruritus

PSORIASIS

Bimekizumab efficacy and safety versus adalimumab in patients with moderate-to-severe plaque psoriasis: Results from a multicenter, randomized, double-blinded active comparator-controlled Phase III trial (BE SURE)
Bimekizumab for the treatment of moderate-to-severe plaque psoriasis with scalp, nail and palmoplantar involvement through 52 weeks: Post-hoc analysis from the BE VIVID Phase III trial
Bimekizumab versus ustekinumab efficacy across subgroups of patients with moderate-to-severe plaque psoriasis: Results from the multicenter, randomized, double-blinded Phase III BE VIVID trial
Bimekizumab versus ustekinumab in plaque psoriasis: Lasting efficacy translates to rapid and sustained improvements in quality of life in the BE VIVID multicenter, randomized, double-blinded Phase III trial
Calcipotriene and betamethasone dipropionate cream combines high efficacy, favorable safety, and treatment preference in a single product for topical treatment of psoriasis
Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: Results from a Phase II, randomized, double-blind, placebo-controlled trial
Efficacy and safety of long-term risankizumab treatment for nail, scalp, and palmoplantar psoriasis: An interim analysis from the open-label extension LIMMitless trial
Efficacy and safety of mirikizumab versus secukinumab and placebo in the treatment of moderate-to-severe psoriasis: 52-week results from OASIS-2, a multicenter, randomized, double-blind study
Halobetasol propionate lotion 0.05% in patients 12 to 16 years, 11 months of age with plaque psoriasis: Results from an open-label study evaluating adrenal suppression potential
Patient perceptions of psoriatic disease in the United States: Results from the US subgroup of the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey
Proactive management with twice-weekly topical Cal/BD foam prolongs treatment efficacy versus reactive management in patients with plaque psoriasis
Rates of treated depression and anxiety among patients with psoriasis or psoriatic arthritis treated with apremilast, biologics, conventional DMARDs, and corticosteroids in a US commercial database
Selective inhibition of tyrosine kinase 2 (TK2) with deucravacitinib compared with Janus kinase (JAK) 1–3 Inhibitors
Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Efficacy and safety in two pivotal Phase III trials

ROSACEA

Integrated safety and efficacy analysis of FMX103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea: Results from two Phase III studies

WOUND HEALING

The treatment of wounds associated with recessive dystrophic epidermolysis bullosa with local injections of gene-corrected, collagen VII-expressing autologous human dermal fibroblasts

ACNE

A prospective, multicenter, randomized, double-blind, vehicle-controlled Phase II study to evaluate the safety and efficacy of a combination of 3% minocycline and 0.3% adapalene topical foam formulation for the treatment of moderate-to-severe acne

Presenters: Del Rosso JQ,¹ Stein Gold L,² Draelos Z,³ Raoof TJ,⁴ Hooper D,⁵ Stuart I⁶

Affiliations: ¹JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; ²Henry Ford Health System, Detroit, MI; ³Dermatology Consulting Services, High Point, NC; ⁴T. Joseph Raoof MD Inc./Encino Research Center, Encino, CA; ⁵Delricht Research, New Orleans, LA; ⁶VYNE Therapeutics Inc., Bridgewater, NJ

Background: FCD105 is a fixed combination of minocycline 3% and adapalene 0.3% formulated as a novel topical foam and intended for the treatment of moderate-to-severe acne vulgaris.

Objective: This study aimed to evaluate the preliminary safety, efficacy, and tolerability of FCD105 topical foam in the treatment of moderate-to-severe acne vulgaris compared to the vehicle foam and the individual active components, minocycline 3% foam and adapalene 0.3% foam, over a 12-week treatment period.

Methods: FX2016-40 was a randomized, multicenter, double-blind, vehicle-controlled, Phase II study. Qualifying subjects were assigned in a 5:3:4:4 ratio to apply one of the following four color-matched treatments once daily for 12 weeks: FCD105 (minocycline 3% plus adapalene 0.3%), vehicle, minocycline 3%, or adapalene 0.3%. Safety and efficacy evaluations were performed at Weeks 4, 8, and 12. Coprimary efficacy endpoints were the absolute change from baseline in inflammatory and non-inflammatory lesions at Week 12 and the proportion of subjects achieving treatment success per Investigator’s Global Assessment (IGA) scores at Week 12.

Results: Of the 447 randomized subjects, 417 completed the study. The majority of subjects were White (70.7%) and female (61.1%) with a mean age of 21 years. FCD105 showed a statistically significant improvement compared to vehicle for the absolute reduction in inflammatory lesions at Week 12, ?19.40 (?64.1% reduction) for FCD105 versus ?15.58 (?50.9% reduction) for vehicle (P=0.0020) and the percent of subjects achieving IGA treatment success, 35.9 percent versus 15.7 percent, respectively (P=0.0003). FCD105 showed a numerical improvement in noninflammatory lesions compared to vehicle. Though the study was not powered to demonstrate differences between FCD105 and its individual active components, the majority of these comparisons did show statistically significant improvements favoring FCD105 at Week 12. Overall, treatment-emergent adverse events (TEAEs) were few in type and frequency (14.8%), with the majority (8.5%) being mild in severity. There were no serious TEAEs. The most common TEAEs occurring in one percent or more of the FCD105 group were upper respiratory tract infection (1.4%), nasopharyngitis (1.4%), dry skin (1.4%), and rash (1.4%). TEAEs leading to study discontinuation occurred in three (2.7%) adapalene subjects (acne n=1, rash n=2) and one (0.7%) FCD105 subject (acne). FCD105 demonstrated a favorable tolerability profile, with most (? 93%) local signs and symptoms being reported as “none” or “mild” in the FCD105 and vehicle groups.

Conclusion: Daily application of FCD105 resulted in significant clinical improvements compared to vehicle while maintaining the favorable safety profile that has been previously demonstrated for each compound.

Efficacy and safety of encapsulated benzoyl peroxide 3% and encapsulated tretinoin 0.1% (E-BPO/E-ATRA) cream in acne vulgaris: Results from two randomized, controlled pivotal clinical trials

Presenters: Del Rosso JQ,¹ Sugarman J,² Levy-Hacham O,³ Mizrahi R³

Affiliations: ¹JDR Research, Las Vegas, NV; ²University of California San Francisco, San Francisco, CA; ³Sol-Gel Technologies Ltd., Ness Ziona, Israel

Background: Benzoyl peroxide (BPO) and tretinoin (ATRA) are widely prescribed and considered to be highly effective drugs in the treatment for acne vulgaris. However, ATRA is degraded by BPO, potentially reducing its efficacy. Microencapsulated benzoyl peroxide 3% and microencapsulated tretinoin 0.1% (E-BPO/E-ATRA) cream is an investigational, antibiotic-free, fixed-dose combination of BPO and ATRA. The use of a microencapsulation technology platform provides a stable combination of BPO and ATRA, reducing the potential for skin irritation.

Methods: A group of 858 patients nine years of age or older with moderate-to-severe acne were enrolled in two double-blind, randomized, vehicle-controlled pivotal trials (Studies SGT-65-04 and SGT-65-05) at 63 sites across the United States (US). Patients were randomized in a 2:1 ratio to 12 weeks of once-daily treatment with either E-BPO/E-ATRA cream (n=571) or vehicle cream (n=287). The coprimary endpoints for both trials were the proportion of patients who achieved at least a two-grade reduction from baseline and clear (Grade 0) or almost clear (Grade 1) at Week 12 on a five-point IGA scale, absolute change from baseline in inflammatory lesion count at Week 12, and absolute change from baseline in noninflammatory lesion count at Week 12.

Results: E-BPO/E-ATRA was significantly superior to vehicle for all primary endpoints in both Phase III trials. In trial SGT-65-04, 38.5 percent of patients treated with E-BPO/E-ATRA achieved success in IGA versus 11.5 percent for vehicle (P<0.001). The respective values in trial SGT-65-05 were 25.4 percent and 14.7 percent (P=0.017). In trial SGT-65-04, the absolute change from baseline in inflammatory lesion count for E-BPO/E-ATRA was ?21.6 versus ?14.8 for vehicle (P<0.001). In trial SGT-65-05, the absolute change from baseline of inflammatory lesion count for E-BPO/E-ATRA was ?16.2 versus ?14.1 for vehicle (P=0.021). In trial SGT-65-04, the absolute change from baseline in noninflammatory lesions for E-BPO/E-ATRA was ?29.7 versus ?19.8 for vehicle (P<0.001). The respective values in study SGT-65-05 were ?24.2 and ?17.4 (P<0.001). E-BPO/E-ATRA was well-tolerated in both studies. The majority of local skin reactions and other adverse events were mild in severity. During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and decreased thereafter. There were no TEAEs and four unrelated serious adverse events (1 E-BPO/E-ATRA, 3 vehicle). Less than five percent of patients discontinued E-BPO/E-ATRA due to adverse events.

Conclusion: Results from the two Phase III trials of E-BPO/E-ATRA demonstrated that this new microencapsulated formulation of BPO and ATRA provided statistically significant and clinical meaningful improvements in IGA and corresponding reductions in both inflammatory and noninflammatory lesions in patients with moderate-to-severe acne. E-BPO/E-ATRA was safe and well-tolerated, with generally mild adverse events and no TEAEs.

Long-term safety and tolerability of sarecycline for the treatment of acne vulgaris: Results from a Phase III, multicenter, open-label study and a Phase I phototoxicity study

Presenters: Pariser DM,¹ Green LJ,² Lain EL,³ Johnson JL,⁴ Grada A⁵

Affiliations: ¹Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; ²George Washington University School of Medicine, Washington, DC; ³Austin Institute for Clinical Research, Pflugerville, TX; ⁴Departments of Dermatology and Pathology, Feinberg School of Medicine, Northwestern University, IL; ⁵R&D and Medical Affairs, Almirall (US), Exton, PA

Background: Sarecycline is an US Food and Drug Administration (FDA)-approved, once-daily, narrow-spectrum, tetracycline-class antibiotic for the treatment of moderate-to-severe acne.

Objective: We sought to evaluate the safety, tolerability, and patterns of use of sarecycline in patients with moderate-to-severe acne vulgaris during a 40-week, Phase III, multicenter, open-label extension study.

Methods: Patients (N=483) aged nine years or older with moderate-to-severe acne who completed one of two prior Phase III, double-blind, placebo-controlled, 12-week trials in which they received sarecycline 1.5mg/kg/day or placebo were included. The primary assessment was the safety of sarecycline 1.5mg/kg/day for 40 weeks as indicated by adverse events (AEs), vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. Patterns of sarecycline use were a secondary assessment.

Results: A total of 354 patients (73.3%) completed the study. The most common reasons for premature discontinuation were withdrawal by the patient (14.5%), loss to follow up (7.9%), and AEs (2.5%). The most common TEAEs were nasopharyngitis (3.7%), upper respiratory tract infection (3.3%), headache (2.9%), and nausea (2.1%). Clinical laboratory evaluations suggested no clinically meaningful differences between the treatment sequences. Rates of TEAEs commonly associated with other tetracycline antibiotics include dizziness (0.4%) and sunburn (0.2%), and for gastrointestinal TEAEs, nausea (2.1%), vomiting (1.9%), and diarrhea (1.0%). Additionally, results of a placebo-controlled, crossover, single-dose, Phase I, phototoxicity study suggest that sarecycline has low potential to cause clinically significant phototoxicity.

Conclusion: Patients aged nine years or older with moderate-to-severe acne vulgaris who received sarecycline once daily for up to 40 weeks showed low rates of TEAEs, with nasopharyngitis, upper respiratory tract infection, headache, and nausea being the only TEAEs reported by two percent or more of patients. No clinically meaningful safety findings were noted.

Financial Disclosures: Financial support provided by Almirall, LLC.

Reduced blood-brain barrier penetration of sarecycline relative to minocycline in rats corresponds with lipophilicity

Presenters: Stein-Gold L,¹ Moore A,^2,3 Tanaka SK,⁴ Johnson JL,⁵ Grada A⁶

Affiliations: ¹Henry Ford Health System, Detroit, MI; ²Baylor University Medical Center, Dallas, TX; ³Arlington Research Center, Arlington, Texas; ⁴Paratek Pharmaceuticals, Inc. King of Prussia, PA; ⁵Departments of Dermatology and Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL; ⁶R&D and Medical Affairs, Almirall, Exton, PA

Background: Sarecycline is an FDA-approved, narrow-spectrum, tetracycline-class oral antibiotic specifically designed for the treatment of moderate-to-severe acne vulgaris. Sarecycline has not been compared head-to-head with other tetracyclines, including doxycycline or minocycline, in any clinical studies. However, historical reports of commonly recognized AEs often associated with tetracycline-class drugs show rates that are generally higher for both doxycycline and minocycline than those reported in the recent clinical trials for sarecycline. In particular, the potentially vestibular-related TEAEs in two Phase III randomized, controlled trials (N=2002) for sarecycline were very low (dizziness [0.5%], vertigo [0%], and tinnitus [0%]; pooled).

Methods: A 40-week, Phase III, open-label extension study (N=483) demonstrated a similar profile. We tested whether sarecycline could cross the blood-brain barrier compared to minocycline using a rat model. Sarecycline or minocycline was delivered intravenously and rat brains were examined one, three, and six hours later. While minocycline was present in the rat brains at all time points, sarecycline remained below the level of quantification (<0.05µg/g). In a separate study, the lipophilicity of sarecycline, doxycycline, and minocycline was tested by determining the octanol/water distribution coefficients at pH levels 5.5 and 7.4.

Results: Minocycline was slightly more lipophilic than doxycycline, which in turn was more lipophilic than sarecycline. For pH 5.5 the distribution coefficients were 0.09±0.02, 0.00±0.02, and ?0.16±0.01, respectively For pH 7.4 the distribution coefficients were 0.12±0.02, ?0.08±0.03, and ?0.26±0.01, respectively.

Conclusion: Sarecycline’s lower lipophilicity corresponds with its lower ability to cross the blood-brain barrier compared to minocycline and might explain the low rate of vestibular adverse events observed in sarecycline’s clinical trials.

Financial Disclosures: Financial support was provided by Almirall, LLC.

ACTINIC KERATOSIS

Favorable safety profile of tirbanibulin ointment 1% for actinic keratosis: Pooled results from two Phase III studies

Presenters: Schlesinger T,¹ Bhatia N,² Berman B,³ Grada A,⁴ Torra A,⁵ Cutler D,⁶ Lebwohl M⁷

Affiliations: ¹Dermatology and Laser Centre of Charleston, Charleston, SC; ²Therapeutics Clinical Research, San Diego, CA; ³Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; ⁴Almirall, Exton, PA; ⁵Almirall, Barcelona, Spain; ⁶Athenex, Inc., Buffalo, NY; ⁷Icahn School of Medicine at Mount Sinai, New York, NY

Background: Tirbanibulin is a first-in-class, novel inhibitor of tubulin polymerization and associated with disruption of Src kinase signaling for actinic keratosis (AK). No cases of contact sensitization or phototoxicity were observed in two Phase I studies (KX01-AK-006/KX01-AK-008).

Objective: We sought to report pooled safety data in adults with AK on the face/scalp from two pivotal Phase III randomized, double-blinded, vehicle-controlled, parallel-group studies (KX01-AK-003/KX01-AK-004).

Methods: Eligible patients with 4 to 8 clinically visible AK lesions in a 25cm² area were randomized 1:1 to receive tirbanibulin ointment 1% or vehicle (5-day once-daily self-application). Safety assessments included local skin reactions (LSRs), including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration (scale of 0–3 [absent–severe]) and AEs up to Day 57. Incidence of maximal postbaseline LSR grades greater than baseline was described by treatment and LSR sign. Pooled LSR composite scores (the sum of all 6 LSRs) by visit and treatment were analyzed.

Results: There were 702 subjects included in the pooled safety population (tirbanibulin n=353; vehicle n=349). Treatment adherence was greater than 99 percent. Demographics were similar between treatment groups; most were White males, Fitzpatrick Skin Type II, with a median of six baseline AK lesions. TEAEs were few; 16 percent of tirbanibulin-treated patients and 10 percent of vehicle-treated patients had one or more TEAEs consisting of mostly transient mild-to-moderate application-site pain and pruritus that did not require treatment. No deaths, discontinuations, or serious AEs related to tirbanibulin occurred. Incidence and severity of LSRs greater than baseline were higher with tirbanibulin versus vehicle. For tirbanibulin, the most commonly occurring LSRs were mild-to-moderate erythema (22% and 63%) and flaking/scaling (26% and 47%), followed by mild crusting (30%) and mild swelling (29%). Regarding composite LSR scores, LSR peaked by Day 8 with tirbanibulin (maximum mean score of 4.1), that decreased significantly by Day 15, and by Day 29 were mostly resolved. By Day 29 and Day 57, mean composite LSR scores were similar between tirbanibulin (0.6 and 0.4, respectively) and vehicle groups (0.6 and 0.5). No significant difference was observed in mean composite LSR score in patients younger and older than 65 years of age (maximum mean LSR: 4). There were no differences in TEAEs according to age, sex, and baseline AK lesions. Overall, incidence of TEAEs was slightly higher for face (17% and 11%) than scalp subjects (13% and 7%) in the tirbanibulin and vehicle groups, respectively.

Conclusion: Pooled data from Phase III studies showed a favorable safety and tolerability profile of tirbanibulin ointment 1% once daily for five consecutive days in the treatment of AK on the face or scalp.

Financial Disclosures: This study was supported by Athenex, Inc.

ALOPECIA

Efficacy and safety of baricitinib in the treatment of patients with severe or very severe alopecia areata: Phase II portion of BRAVE-AA1 randomized controlled trial

Presenters: King B,¹ Ko J,² Forman S,³ Ohyama M,⁴ Mesinkovska N,⁵ Yu G,⁶ McCollam J,⁶ Gamal M,^6, Janes J,⁶ Edson-Heredia E,⁶ Holzwarth K,⁶ Dutronc Y⁶

Affiliations: ¹Yale School of Medicine, New Haven, CT; ²Stanford University, Stanford, CA; ³ForCare Clinical Research, FL; ⁴Kyorin University Faculty of Medicine, Tokyo, Japan; ⁵University of California, CA; ⁶Eli Lilly and Company, Indianapolis, IN

Background: Alopecia areata (AA) is an autoimmune disorder associated with poor quality of life and psychological comorbidities. There are currently no FDA-approved treatments for AA. The ongoing BRAVE-AA1 trial will evaluate the efficacy and safety of baricitinib, an oral, reversible, and selective Janus kinase (JAK)1 and JAK 2 inhibitor, in patients with scalp hair loss of 50 percent or greater.

Objective: This study aims to report efficacy and safety of baricitinib in the Phase II portion of the trial by conducting interim analyses.

Methods: BRAVE-AA1 is an ongoing Phase II/III study with an adaptive, operationally seamless design. The Phase III portion was designed to identify up to two doses for the Phase III portion of study. Eligibility criteria included a current episode of AA lasting for six months to eight years, Severity of Alopecia Tool (SALT) score 50 or greater, and no spontaneous improvement over six months prior to screening. Other treatments for AA were prohibited during the study and patients with prior inadequate response to JAK inhibitor were excluded. In the Phase II portion, patients were randomized 1:1:1:1 to receive placebo (n=28), baricitinib 1mg (n=28), 2mg (n=27), or 4mg (n=27) once daily. Interim analyses were conducted after patients completed 12 and 36 weeks of treatment, respectively. Primary outcome was the proportion of patients achieving a SALT score of 20 or less (indicating a clinically meaningful improvement) at Week 36. Logistic regression with nonresponder imputation and analysis of covariance models with modified last observation carried forward imputation were used.

Results: Week 12 interim analysis demonstrated numerical superiority of baricitinib 2mg (29.6%), and 4mg (33.3%) doses over 1mg dose (17.9%), and placebo (10.7%) for at least a 30-percent improvement from baseline in SALT score. Hence, 2mg and 4mg doses were selected for the Phase III program. At Week 36, the proportion of patients achieving SALT ?20 was significantly greater in baricitinib 2mg (33.3%, p=0.016), and 4mg (51.9%, p=0.001) groups compared to placebo (3.6%). The proportion of patients achieving score of 0 (no hair loss)/1 (limited) on the patient-reported outcome (PRO) for scalp hair assessment, were significantly greater in 2mg, and 4mg groups compared to placebo (p<0.05). The proportion of patients achieving a score of 0 (full)/1 (minimal gaps and even distribution/spacing) on clinician-reported outcomes (ClinRO) and PRO measures for eyebrow and eyelash hair loss was significantly greater in the 4mg group (p<0.05 vs. placebo). The most common AE was upper respiratory tract infection, which occurred in 17.9 percent, 11.1 percent, and 22.2 percent of patients in placebo, 2mg and 4mg groups, respectively. No serious AEs, deaths, thrombotic events, or new safety concerns were reported.

Conclusion: These results support the potential of baricitinib in the treatment of patients with AA with scalp hair loss of 50 percent or greater.

Financial Disclosures: This study was sponsored by Eli Lilly and Company, under license from Incyte Corporation.

ATOPIC DERMATITIS

Clinical tailoring of baricitinib 2mg in atopic dermatitis: Baseline body surface area and rapid onset of action identifies response at Week 16

Presenters: Silverberg JI,¹ Boguniewicz M,² Waibel J,³ Weisman J,⁴ Strowd L,⁵ Sun L,⁶ Ding Y,⁶ Goldblum O,⁷ Nunes FP,⁶ Simpson EL⁸

Affiliations: George Washington University School of Medicine, Washington, DC; ²Division of Allergy-Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, CO; ³Miami Dermatology and Laser Institute, Miami, FL; ⁴Medical Dermatology Specialists, Atlanta, GA; ⁵Wake Forest University School of Medicine, Winston-Salem, NC; ⁶Eli Lilly and Company, Indianapolis, IN; ⁷Formerly with Eli Lilly and Company, Indianapolis, IN; ⁸Oregon Health and Science University, Portland, OR

Background: Baricitinib, an oral Janus kinase JAK1/JAK2 inhibitor, improved disease in moderate-to-severe atopic dermatitis (AD) in five randomized, placebo-controlled, Phase III trials. Understanding the patient population who will benefit most from treatment with baricitinib 2mg based on clinical trial data would significantly improve patient experience with treatment.

Objective: Here, we present results from a post-hoc analysis aiming to identify responders to baricitinib 2mg with a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement from the Phase III monotherapy trial BREEZE-AD5 (NCT03435081).

Methods: Classification and regression trees were applied to baseline patient demographics and disease characteristics to identify a patient population most likely to benefit from baricitinib 2mg therapy. Two-by-two contingency tables evaluated the association between speed of onset on improvement in skin inflammation or itch (assessed at Week 4 or Week 8) and response at Week 16 for the proportion of patients achieving at least a 75-percent improvement in Eczema Area and Severity Index (EASI75), validated Investigator Global Assessment for AD (vIGA-AD™) score of 0 or 1, or at least a four-point improvement in Itch (Itch ? 4). Missing data due to rescue or treatment discontinuation were imputed as nonresponder. Response rates were also summarized over time for identified subgroups.

Results: Baseline BSA of 10 to 50 percent was associated with improved clinical response to baricitinib 2mg. At Week 16, EASI75 was achieved by 37.5 percent of baricitinib 2mg-treated patients with baseline BSA 10 to 50 percent compared to 9.5 percent of patients with BSA over 50 percent. Similarly, at Week 16, vIGA-AD (0,1) was achieved by 31.7 percent of baricitinib 2mg-treated patients with baseline BSA 10 to 50 percent compared to 4.8 percent of patients with BSA over 50 percent. Early meaningful response, defined as at least a 50-percent improvement in BSA or a 3-point or greater improvement in itch from baseline at Week 4 or Week 8, was able to further refine which patients were most likely to benefit from baricitinib 2mg therapy. Early response in skin inflammation or itch at Week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ? four of 55.4 percent, 48.2 percent, and 39.3 percent at Week 16. Assessment of early response at Week 8 was associated with EASI75, vIGA-AD (0,1), and Itch ? 4 of 66.7 percent, 56.1 percent, and 42.1 percent at Week 16.

Conclusion: There are currently multiple therapies in development for AD. Understanding which patients are likely to benefit most from therapy, and which patients should not be considered for a given treatment can significantly improve patient experience with treatment, increase the cost effectiveness of a therapy, and ensure that only patients who are likely to benefit from therapy are exposed to a drug. This analysis suggests that patients with moderate-to-severe AD affecting between 10 to 50 percent of their BSA account for the majority of responders to baricitinib 2mg. In addition, due to rapid onset of response, clinical assessment of patients after 4 or 8 weeks of initiation of baricitinib 2mg treatment showed a meaningful clinical benefit to patients, providing positive feedback to patients who are likely to benefit from long-term therapy and allowing for rapid decision on discontinuation of treatment in those who are not likely to benefit from baricitinib 2mg.

Conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: Pooled results from five clinical trials

Presenters: Wollenberg A,¹ Beck LA,² Weller MB,³ Zachariae R,⁴ Olsen CK,⁴ Thyssen JP⁵

Affiliations: ¹Clinic of the University of Munich, Clinic and Polyclinic for Dermatology and Allergology, Munich, Germany; ²Department of Dermatology, Medicine and Pathology, University of Rochester Medical Center, Rochester, NY; ³Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, Netherlands; ⁴LEO Pharma A/S, Ballerup, Denmark; ⁵Department of Dermatology and Allergy, Herlev-Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

Background: AD is a common chronic inflammatory skin disease. Ocular comorbidities, including various forms of conjunctivitis, are commonly present in patients with AD. This has been reflected in clinical trials of moderate-to-severe patients with AD. Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin (IL)-13, a key cytokine in AD. Here, we report an overview of key conjunctivitis data from the Phase IIB and Phase II ECZTRA trials of tralokinumab in patients with AD.

Methods: Patients treated with tralokinumab 300mg or placebo every two weeks were pooled from five clinical trials: the Phase III ECZTRA 1 and 2 trials (tralokinumab monotherapy) and ECZTRA 3 trial (tralokinumab in combination with topical corticosteroids), the Phase II ECZTRA 5 trial (vaccine response in tralokinumab-treated patients with AD), and the Phase IIB trial (efficacy and safety evaluation of tralokinumab). AEs were summarized for the initial treatment period (16 weeks for ECZTRA and 12 weeks for Phase IIB). Conjunctivitis was defined as an AE of special interest (AESI). Cochran-Mantel-Haenszel weights were applied to calculate adjusted AE incidences to account for different randomization rates between tralokinumab and placebo.

Results: Adult patients treated with tralokinumab (n=1605) or placebo (n=680) were included in the analysis. During the initial treatment period, a conjunctivitis AESI (preferred terms conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, and conjunctivitis viral) occurred in 126 patients (7.5%) treated with tralokinumab versus 21 (3.2%) with placebo. Overall, 145 and 23 conjunctivitis events occurred in the tralokinumab and placebo groups, respectively. The majority were mild (68% vs. 65%) or moderate (30% vs. 35%) in severity; ophthalmologists confirmed 29 percent of conjunctivitis events across the tralokinumab (37 events) and placebo (5 events) groups. A similar percentage of events in the tralokinumab and placebo groups, respectively, resolved (78.6% vs. 73.9%) or were resolving (2.8% vs. 4.3%) during the initial treatment period. No events were serious, and two events led to permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis was observed in patients with AD with more severe disease and a previous history of allergic conjunctivitis. Median time to first event was similar for both groups (50.0 days vs. 54.0 days); however, duration of conjunctivitis was longer in the tralokinumab (21.0 days vs. 14.0 days) group. The majority of patients (81% of tralokinumab-treated patients vs. 63% of those who received placebo) received treatment for their conjunctivitis. Common treatments included ophthalmic anti-allergics (28% vs. 42%), anti-infectives (30% vs. 11%), corticosteroids (22% vs. 11%), and combined corticosteroids and anti-infectives (13.5% vs. 15.8%).

Conclusion: The overall incidence of conjunctivitis, identified as an AESI in the initial treatment period of the AD pool, was higher for tralokinumab than for placebo, but the majority of cases were mild or moderate in severity. The majority of conjunctivitis events received treatment and resolved or were resolving during the trials.

Financial Disclosures: The ECZTRA trials were sponsored by LEO Pharma A/S. The tralokinumab Phase IIB trial was sponsored by MedImmune/AstraZeneca.

Dupilumab treatment provides improvements in signs of AD at Week 100 in adult patients with moderate-to-severe AD who did not achieve ? 75-percent reduction in Eczema Area and Severity Index at Week 16

Presenters: Armstrong A,¹ Blauvelt A,² Simpson EL,³ Chen Z,⁴ Ardeleanu M,⁴ Rossi AB,⁵ Tomondy P⁵

Affiliations: ¹Keck School of Medicine, University of Southern California, Los Angeles, CA; ²Oregon Medical Research Center, Portland, OR; ³Oregon Health and Science University, Portland, OR; ⁴Regeneron Pharmaceuticals, Inc., Tarrytown, NY; ⁵Sanofi Genzyme, Cambridge, MA

Background: AD is a chronic inflammatory skin disease that can require long-term management.

Objective: Here, we report dupilumab efficacy up to Week 100 in an open-label extension (OLE) study (NCT01949311) of adult patients with moderate-to-severe AD who did not have an improvement of 75 percent or greater in EASI-75 or an IGA of 0/1 at Week 16 during their parent study.

Methods: Patients included in this analysis participated in parent studies LIBERTY AD SOLO 1 or 2 (SOLO1&2; NCT02277743, NCT02277769) and were subsequently enrolled in LIBERTY AD OLE, assessing long-term safety and efficacy, where all patients received dupilumab 300mg weekly (QW). Included in this analysis are patients who previously received dupilumab in SOLO 1&2, and subsequently enrolled in OLE, who did not achieve either EASI-75 or IGA 0/1 at Week 16 of SOLO1&2.

Results: 460/457/462 patients enrolled in SOLO 1&2 in the placebo, dupilumab 300mg Q2W, and dupilumab 300mg QW groups, respectively. Most patients who achieved the primary endpoints of SOLO 1&2 continued into SOLO-CONTINUE (NCT02395133); most patients who did not achieve the primary endpoints of SOLO 1&2 entered OLE. 213/178 patients entered OLE from SOLO 1&2 (receiving dupilumab 300mg Q2W, and dupilumab 300mg QW in SOLO 1&2, respectively). At least 91.5 percent of these patients did not achieve either EASI-75 or IGA 0/1 at Week 16 of SOLO 1&2 and were included in this analysis. Proportions of patients with EASI-75 at Week 100 of the OLE were 91.0 percent and 91.1 percent for the SOLO1&2 dupilumab 300mg Q2W and dupilumab 300mg QW treatment groups, respectively. Similarly, at Week 100 of the OLE, proportions of patients with IGA scores of 0 or 1 were 44.8 percent and 49.0 percent for the patients who received dupilumab 300mg Q2W and dupilumab 300mg QW, respectively, in SOLO1&2.

Conclusion: Among patients with moderate-to-severe AD not achieving EASI-75 or IGA 0/1 at Week 16 in SOLO 1&2, a large proportion achieved these respective endpoints after continued treatment with dupilumab 300mg QW. These OLE data suggest that long-term treatment with dupilumab improves AD signs in patients who do not respond optimally in the short term, independent of parent-study treatment dose.

Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Pooled analysis of two Phase III, randomized, double-blind studies

Presenters: Papp K,¹ Szepietowski JC,² Kircik L,³ Toth D,⁴ Kuligowski ME,⁵ Venturanza ME,⁵ Sun K,⁵ Simpson EL⁶

Affiliations: ¹K. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada; ²Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland;³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴XLR8 Medical Research and Probity Medical Research, Windsor, Ontario, Canada; ⁵Incyte Corporation, Wilmington, DE; ⁶Oregon Health & Science University, Portland, OR

Background: AD is a chronic, intensely pruritic, inflammatory skin dermatosis. JAKs act downstream of proinflammatory cytokines and itch mediators involved in AD pathogenesis. Ruxolitinib (RUX) cream selectively inhibits JAK1 and JAK2.

Objective: Here, we report the eight-week efficacy and safety of RUX cream using pooled data from two Phase III studies in adolescent and adult patients with AD.

Methods: Two identical studies (TRuE-AD1 [NCT03745638] and TRuE-AD2 [NCT03745651]) enrolled patients aged 12 years or older with AD for two years or more, an IGA score of 2 or 3, and 3 to 20-percent affected BSA. In both studies, patients were randomized (2:2:1) to twice-daily 0.75% RUX cream, 1.5% RUX cream, or vehicle cream for eight weeks of double-blind treatment. Patients on RUX subsequently continued treatment for 44 weeks; patients initially randomized to vehicle were re-randomized 1:1 to either RUX regimen. The primary endpoint was IGA treatment success (TS) at Week 8 (IGA of 0 or 1 and a ? 2-grade improvement from baseline). Secondary endpoints at Week 8 versus baseline included EASI-75, at least a four-point improvement in itch Numerical Rating Scale score (NRS4), at least a six-point improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form–Sleep Disturbance (8b) score (24-hour recall), and safety.

Results: Of 1249 randomized patients, 130 (10.4%) discontinued treatment. The median (range) age was 32.0 (12–85) years; 19.6 percent were adolescents and 61.7 percent were female. The efficacy population consisted of 1,208 patients (vehicle, n=244; 0.75% RUX, n=483; 1.5% RUX, n=481). All randomized patients were included in the safety population. Significantly more patients treated with either RUX cream regimen achieved IGA-TS at Week 8 (44.7%/52.6% for 0.75%/1.5% RUX) versus vehicle (11.5%; both P<0.0001). EASI-75 at Week 8 was achieved by 53.8 percent/62.0 percent of patients who applied 0.75%/1.5% RUX versus 19.7 percent on vehicle (both P<0.0001). Substantially greater itch reduction was observed within 12 hours of first RUX cream application (mean change from baseline, ?0.4/?0.5 for 0.75%/1.5% RUX) versus vehicle (?0.1; both P<0.02). At Week 8, more patients who applied RUX cream achieved NRS4 (41.5%/51.5% for 0.75%/1.5% RUX) versus vehicle (15.8%; both P<0.0001). Considerable improvement in PROMIS 8b was achieved with both RUX cream regimens at Week 8 (20.9%/23.8% for 0.75%/1.5% RUX) versus vehicle (14.2%; both P<0.05). Treatment-related adverse events (AEs) were reported in 4.7 percent of patients who applied RUX cream (combined) versus 11.2 percent of patients who applied vehicle. No AEs indicative of systemic activity of RUX were observed. No serious AEs related to RUX were reported.

Conclusion: Ruxolitinib cream showed anti-inflammatory and antipruritic effects with superior efficacy versus vehicle for IGA-TS, EASI-75, itch NRS4, and PROMIS 8b. The AE profile was similar to vehicle; the rate of application site reactions was low. These results demonstrate the potential of RUX cream as an effective and well-tolerated topical treatment for AD.

Financial Disclosures: KP reports honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly, Galderma, Genentech, Gilead, GSK, InflaRx, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB.

JCS has served as an advisor for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, and Trevi; has received speaker honoraria from AbbVie, Janssen-Cilag, LEO Pharma, Novartis, Sanofi-Genzyme, Sun Pharma, and Eli Lilly; and has received clinical trial funding from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte Corporation, InflaRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB.

LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte Corporation, Kamedis, LEO Pharma, L’Oreal, Menlo, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro.

DT has served as an investigator for AbbVie, Avillion, Amgen, Arcutis, Astellas, Astion, Boehringer Ingelheim, Celgene, Dermira, DS BioPharma, Dow Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche Ltd, Galderma, GlaxoSmithKline, Incyte Corporation, Isotechnika, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and UCB Biopharma.

MEK, MEV, and KS are employees and shareholders of Incyte Corporation.

ELS is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte Bio, Galderma, Incyte Corporation, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant.

Laboratory safety of dupilumab in adolescent patients with atopic dermatitis: 52-week laboratory safety findings from an open-label study (LIBERTY AD PED-OLE)

Presenters: Cork MJ,¹ Lockshin B,² Blauvelt A,³ Chen Z,⁴ Prescilla R,⁵ Bansal A⁴

Affiliations: ¹University of Sheffield, Sheffield, United Kingdom; ²Georgetown University, Rockville, MD; ³Oregon Medical Research Center, Portland, OR; ⁴Regeneron Pharmaceuticals, Inc., Tarrytown, NY; ⁵Sanofi Genzyme, Cambridge, MA

Background: Until recently, adolescents with moderate-to-severe AD inadequately controlled by topical therapies had limited treatment options.

Objective: Here, we report laboratory outcomes from an open-label, long-term trial of dupilumab in AD patients aged 12 to younger than 18 years (LIBERTY AD PED-OLE; NCT02612454).

Methods: An ongoing, Phase III, open-label extension (OLE) study in patients aged six months to 18 years with AD who participated in previous dupilumab studies. The original dosing regimen of 2mg/kg or 4mg/kg weekly was changed to a fixed-dose regimen of 300mg every four weeks; the dose could be up-titrated at the discretion of the investigators in case of inadequate clinical response at Week 16 as follows: patients <60kg: 200mg every two weeks (Q2W); patients ? 60kg: 300mg Q2W. The treatment period for patients enrolled in the original mg/kg dosing regimen was up to 104 weeks with the option of extending the treatment period until dupilumab regulatory approval. Patients enrolled in the fixed-dose group were treated until regulatory approval of dupilumab for their specific age group in their geographic region. Concomitant topical corticosteroids/calcineurin inhibitors were allowed without restriction; systemic AD medications were not permitted except as rescue treatment. Patients who had a sustained remission of AD, defined as maintenance of an IGA score of 0 or 1 continuously for a 12-week period after Week 40, discontinued dupilumab. We evaluated laboratory safety data for patients aged 12 to 18 years (Data cutoff date: December 15, 2018; N=299; 105 patients completed up to Week 52).

Results: Laboratory assessments were performed for patients at Week 0 (OLE baseline), Week 16, and Week 52. Mean eosinophil counts (x109/L) remained within normal range up to Week 52 (Week 0: 0.7; Week 16: 0.7; Week 52: 0.6). Mean leukocytes (x109/L; Week 0: 7.5; Week 16: 7.3 ; Week 52: 7.4), neutrophils (x109/L; Week 0: 4.1; Week 16: 4.0; Week 52: 4.1), hemoglobin (g/L; Week 0: 139.0; Week 16: 140.9; Week 52: 139.7), and platelets (x109/L; Week 0: 292.5; Week 16: 284.0; Week 52: 139.7) also remained within normal range. No clinically relevant changes were observed for chemistry parameters (creatinine kinase, albumin, protein, bilirubin, potassium, ALP, creatinine, blood urea nitrogen, lactate dehydrogenase, and glucose). The safety profile was consistent with the known dupilumab safety profile.

Conclusion: No clinically meaningful changes in laboratory parameters occurred with 52 weeks of dupilumab treatment in adolescents with AD, similar to previous findings in adults. These findings indicate that routine laboratory monitoring for hematology and chemistry parameters is not required in this population before initiation or during treatment with dupilumab.

Laboratory safety of dupilumab in pediatric patients aged 6 to 12 years with severe atopic dermatitis: Results from a Phase III trial (LIBERTY AD PEDS)

Presenters: Wollenberg AD,¹ Thaçi D,²Cork MJ,³ Arkwright PD,⁴ Gooderham M,⁵ Sun X,⁶ O’Malley JT,⁷ Khokhar FA,⁶ Bansal A,⁶ Shumel B⁶

Affiliations: ¹Ludwig-Maximilian University, Munich, Germany; ²University of Lübeck, Lubeck, Germany; ³University of Sheffield, Sheffield, United Kingdom; ⁴University of Manchester, Manchester, United Kingdom; ⁵SKiN Centre for Dermatology, and Queen’s University, Kingston, Ontario, Canada; ⁶Regeneron Pharmaceuticals, Inc., Tarrytown, NY; ⁷Sanofi, Cambridge, MA

Background: Most current systemic treatments for moderate-to-severe AD require serial laboratory assessments to ensure patient safety. Dupilumab has demonstrated significant clinical improvement with a favorable risk-benefit profile in adults and adolescents with moderate-to-severe AD inadequately controlled with topical medications and in children aged 6 to younger than 12 years with severe AD. Moreover, no clinically important changes in hematology, serum chemistry, and urinalysis parameters have been reported for dupilumab-treated adults and adolescents. The impact of dupilumab treatment on laboratory values in children aged 6 to younger than 12 years with severe AD is not known.

Methods: In LIBERTY AD PEDS (NCT03345914), a multicenter, Phase III trial, 367 patients aged 6 to younger than 12 years were randomized 1:1:1 to subcutaneous dupilumab every two weeks (Q2W; 100mg if baseline weight <30 kg, 200mg if ?30 kg) or every 4 weeks (Q4W; 300mg), or placebo for 16 weeks. All patients received concomitant medium-potency topical corticosteroids. Laboratory values for hematology parameters and serum chemistry were assessed at baseline and Weeks 4, 8, and 16.

Results: Safety was assessed in 362 patients (Q2W/Q4W/placebo: n=122/n=120/n=120). At baseline, treatment groups had similar demographic, clinical, and laboratory characteristics. Baseline mean eosinophil counts were 0.82/0.83/0.85 (x109/L) for Q2W/Q4W/placebo. Increases from baseline in mean eosinophil counts (x109/L) were observed in all groups, with the highest mean increase at Week 8 for placebo (+0.10) and dupilumab Q4W (+0.17), and at Week 16 for dupilumab Q2W (+0.25). No clinically treatment-related relevant events were associated with eosinophilia. There were no meaningful trends in mean changes from baseline in leukocyte counts (x109/L; Q2W ?0.10; Q4W ?0.19; placebo ?0.14) or hemoglobin levels (g/L; Q2W ?1.5; Q4W ?1.6; placebo +0.4) at Week 16. Mean platelet values were lower in both dupilumab groups compared to baseline at Weeks 4/8/16 (x109/L, Q2W ?19.3; Q4W ?18.8; placebo +5.0 at Week 16), but remained within normal range. There were no clinically meaningful trends in mean changes from baseline in chemistry parameters in any group. Mean decreases from baseline in lactate dehydrogenase (LDH) were observed in both dupilumab groups up to Week 16 (U/L, Q2W ?42.2; Q4W ?39.4; placebo ?0.4 at Week 16).

Conclusion: There were no clinically important changes in laboratory parameters attributable to dupilumab treatment in children aged six to younger than 12 years with severe AD in LIBERTY AD PEDS. Consistent with a reduction in systemic inflammation, decreases in platelet counts and LDH levels, both considered acute-phase reactants, were observed in both the dupilumab Q2W and Q4W groups.

Onset of symptom relief reported in daily diaries in patients with atopic dermatitis treated with baricitinib in a US clinical trial

Presenters: Rosmarin R,¹ Casillas M,² Chen S,³ Dawson Z,² Zhang H,⁴ Bukhalo M,⁵ Smith S⁶

Affiliations: ¹Tufts Medical Center, Medford, MA; ²Eli Lilly and Company, Indianapolis, IN; ³Syneos Health, Morrisville, NC; ⁴TechData Service, King of Prussia, PA; ⁵Arlington Dermatology, Rolling Meadows, IL; ⁶California Dermatology and Clinical Research Institute, Encinitas, CA

Background: Itch and sleep disturbance are among the most burdensome symptoms associated with AD. It is important for AD treatments to have rapid onset of action to quickly improve quality of life and relieve suffering.

Objective: The objective of this study was to demonstrate baricitinib 2mg in reducing itch and sleep disturbance within the first week of treatment initiation.

Methods: In a large randomized, double-blind, placebo-controlled clinical trial, patients with AD were randomized to receive baricitinib 2mg (n=133) or placebo (n=136). All patients kept daily electronic diaries, recording outcomes including occurrence and severity of itch and sleep disturbance. Itch was assessed using the Itch Numeric Rating Scale (NRS) measuring itch severity on an 11-point scale (0=no itch, 10=worst itch imaginable). Sleep disturbance was measured using the Atopic Dermatitis Sleep Scale Item 2 (ADSS2), a measure of the number of nighttime awakenings because of itch. Outcomes were reported as percent change from baseline in least square (LS) means (Day 1 through Day 7). Mixed model repeated measures analysis was used to analyze change from baseline values. Data after any rescue therapy or discontinuation were considered missing from the analysis.

Results: Baseline mean Itch NRS: placebo 7.04, baricitinib 7.31; baseline mean ADSS2: placebo 2.18, baricitinib 2.32. Based on Itch NRS, patients receiving baricitinib had a 9.87 LS mean percent change from baseline (p<.0001) at Day 2 (1 day after initial dose); the placebo group LS mean percent changes were similar to baseline (LS mean change ?1.53%; p=0.3205). The difference between the treatment groups was statistically significant (LS mean difference ? 8.34%; 95% CI ?12.66% to ?3.89%; p=0.0002) and clinically meaningful. By Day 7, the between-group difference widened (LS mean difference ?12.52%; 95% CI ?17.66% to ?7.23%; p<0.0001). Patients receiving baricitinib reported reduced sleep disturbance, as measured by the ADSS2. At Day 2, the LS mean percent change was ?25.21 (p<0.0001) from baseline in the baricitinib group while remaining statistically unchanged in the placebo group (LS mean percent change ?3.85%; p=0.4378). The between-group difference in LS means was ?21.37% (95% CI ?35.47% to ?7.69%; p=0.0025). Baricitinib continued to exhibit a statistically significant difference from placebo in sleep symptoms at Day 7 (LS mean difference ?23.93%; 95% CI ?38.46% to ?9.83%; p=0.0010).

Conclusion: Baricitinib 2mg provided rapid relief from itching and sleep disturbance in patients with AD, with significant relief beginning the second day of treatment.

Rapid itch improvement in children with severe atopic dermatitis treated with dupilumab: A Phase III subset analysis

Presenters: Yosipovitch G,¹ Silverberg JI,² Wu JJ,³ Chen Z,⁴ Prescilla R,⁵ Rossi AB,⁵ Delevry D⁴

Affiliations: ¹University of Miami Miller School of Medicine, Miami, FL; ²George Washington University School of Medicine and Health Sciences, Washington, DC; ³Dermatology Research and Education Foundation, Irvine, CA; ⁴Regeneron Pharmaceuticals, Inc, Tarrytown, NY; ⁵Sanofi Genzyme, Cambridge, MA

Background: In LIBERTY AD PEDS (NCT03345914), a 16-week double-blind, placebo-controlled, Phase III trial, dupilumab significantly improved AD signs and symptoms in children with severe AD.

Objective: Here, we assess time to onset of pruritus improvement in children with severe AD treated with dupilumab FDA-approved doses.

Methods: Children aged 6 to younger than 12 years were randomized to dupilumab 300mg every four weeks (300 Q4W, baseline weight <30kg; 600mg loading dose), 200mg every two weeks (200 Q2W, baseline weight ? 30kg; 400mg loading dose), or placebo. All patients received concomitant medium-potency topical corticosteroids (TCS). We report change from baseline in daily Peak Pruritus Numerical Rating Scale (NRS) scores and proportion of patients who achieved four-point improvement or greater from baseline in Peak Pruritus NRS.

Results: There were 243 patients included in this post-hoc analysis (300 Q4W+TCS/ placebo+TCS<30kg/ 200 Q2W+TCS/ placebo+TCS ? 30kg, n=61/61/59/62). Mean percent change from baseline (standard error) in daily Peak Pruritus NRS decreased after a single dose of dupilumab, as early as Day 8 in the dupilumab 300 Q4W group versus control (

?13.8% [2.9] vs. ?5.1% [2.9]; P<0.05) and Day 16 for children treated with dupilumab 200 Q2W versus control (?22.1% [3.4] vs. ?12.6% [3.3]; P<0.05). A higher proportion of dupilumab-treated patients showed clinically meaningful response (?4-point improvement) in Peak Pruritus NRS versus control, as early as Week 3 in the dupilumab 300q4w group (14.8% vs. 3.3%; P<0.05) and Week 5 in the dupilumab 200 Q2W group (28.1% vs. 12.9%; P<0.05).

Conclusion: Dupilumab+TCS treatment provided rapid and clinically meaningful improvement in intensity and frequency of itch in children with severe AD.

Results from ADVISE: A randomized, double-blind, placebo-controlled Phase II study of etrasimod, an oral, selective, sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis

Presenters: Silverberg JI,¹ Bissonnette R,² Kircik L^3,4 Murrell DF,⁵ Ahluwalia G,⁶ Selfridge A,⁶ Liu K,⁶ Guttman-Yassky E³

Affiliations: ¹Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC; ²Innovaderm Research, Montreal, Quebec, Canada; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Indiana University Medical Center, Indianapolis, IN; Physicians Skin Care, Louisville, KY; DermResearch, PLLC, Louisville, KY; and Skin Sciences, PLLC, Louisville, KY; ⁵Department of Dermatology, St. George Hospital, Faculty of Medicine, University of New South Wales, Sydney, Australia; ⁶Arena Pharmaceuticals, Inc., San Diego, CA

Background: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor 1,4,5 (S1P1,4,5) modulator in development for multiple immune-mediated inflammatory disorders. S1P1 regulates migration of lymphocytes out of lymphatic tissues and dendritic cell migration to lymph nodes. Etrasimod acts as a functional antagonist by inducing sustained receptor internalization of the S1P1 receptors, preventing lymphocyte migration from lymphatic tissue and reduction in peripheral lymphocytes available for recruitment to sites of inflammation without broad immunosuppression.

Objective: This study assessed the efficacy and safety of etrasimod, the first oral S1P receptor modulator to be evaluated in patients with moderate-to-severe AD.

Methods: Participants with chronic AD for at least one year, EASI score of 16 or greater, validated Investigator’s Global Assessment (vIGA) score of 3 or greater, and at least 10-percent affected BSA were randomized 1:1:1 to once-daily etrasimod 1 or 2mg or placebo for 12 weeks (NCT04162769). After a one-week run-in with emollient, participants were randomized 1:1:1 to once-daily etrasimod 1mg or 2mg or placebo. The primary efficacy endpoint was percent change in EASI from baseline at Week 12. A key secondary endpoint was achievement of vIGA score of 0 or 1 with a reduction from baseline of two or more.

Results: Of 140 participants randomized, 80 percent completed 12 weeks. Most participants (82.9%) had moderate vIGA-AD scores at baseline. The proportion of participants receiving etrasimod 2mg who achieved vIGA zero or one increased over time without plateau of effect. At Week 12, a significantly greater proportion of participants receiving etrasimod 2mg vs placebo achieved vIGA zero or one (29.8% vs. 13.0%, P=0.0450). Percent improvement from baseline in EASI score was significantly greater with etrasimod 2mg versus placebo at Week 4 (38.4% vs. 23.4%, P=0.0232) and numerically superior at Week 12 (56.8% vs. 48.5%; P=0.1966). A post-hoc treatment completer analysis excluding participants with dose interruption showed significant improvements at Week 12 for etrasimod 2mg versus placebo in proportion of participants achieving vIGA 0 or 1 (36.8% vs. 13.0%; P=0.0115). Percent improvement from baseline in EASI score was significantly greater with etrasimod 2mg versus placebo at Week 4 (39.8% vs. 23.7%; P=0.0195) and Week 12 (62.1% vs. 48.8%; P=0.0414) without plateau of effect. Etrasimod 1mg did not demonstrate statistical difference from placebo in either vIGA 0 or 1 or in percent improvement in EASI at Week 12. There were no reported serious adverse events (SAEs). In participants receiving etrasimod, the most common AEs (>5% and greater than placebo) were nausea, constipation, back pain, and dizziness. There were no reported cardiac AEs, venous thromboembolism, macular edema, or opportunistic or serious infections in participants receiving etrasimod.

Conclusion: Treatment with etrasimod showed dose-dependent efficacy with the 2mg dose showing significant separation from placebo at both Weeks 4 and 12 across key efficacy endpoints and no plateau of effect at Week 12, as well as good tolerability. These results support the rationale of S1P1,4,5 receptor modulation as a viable mechanism of action for the treatment of AD and warrants further investigation in Phase III clinical trials.

Financial Disclosures: The study was supported by Arena Pharmaceuticals, Inc.

Risk of venous thromboembolism among patients with atopic dermatitis: A cohort study in a US administrative claims database

Presenters: Meyers K,¹ Goodloe R,¹ Pierce E,¹ Rueda MJ,¹ Silverberg JI,² Deberdt W,¹ Brinker D¹

Affiliations: Eli Lilly and Company, Indianapolis, IN; ²George Washington University, Washington, DC

Background: JAK inhibitors, such as baricitinib, tofacitinib, and upadacitinib, have been approved for the treatment of rheumatoid arthritis and select JAK inhibitors are currently in development for treatment of moderate-to-severe AD. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is included as an adverse drug reaction in labels for multiple JAK inhibitors. Yet, background risk of VTE in patients with AD is unknown.

Objective: This study was conducted to understand the risk of VTE among these patients and compare the risk with a matched general population.

Methods: A retrospective cohort study was conducted using data from MarketScan, an administrative claims database from the US. Patients were included if enrolled in the database between January 1, 2012, and October 31, 2017, 18 years of age or older, diagnosed with AD by a dermatologist, and enrolled for 365 days or longer prior to the date of first qualifying AD diagnosis. Patients with prior history of VTE or who received anticoagulation therapy in the one-year period prior to index were excluded. VTE incidence rates (IR)/100 patient-years at risk were reported in overall AD cohort (cohort-1), sub-cohort with moderate-to-severe AD (cohort-2), and the general population that was age-sex-calendar time matched to cohort-1. Cohort-2 was selected based on use of medications such as high-or ultra-high potency topical corticosteroids, systemic corticosteroids, phototherapies, or systemic immunosuppressants. Cox proportional hazards regression was used to estimate hazard ratios (HR) of VTE in AD cohorts 1 and 2, compared to general population adjusting for VTE risk factors.

Results: Of 198,699 patients in the overall AD cohort, 113,927 (57%) patients had moderate-to-severe AD. After 1:1 matching on age category, sex, and calendar time, there were total of 198,685 patients in each of the cohort-1 and the general population. Crude IRs for VTE were 0.24, 0.31, and 0.25 in cohort-1, cohort-2 and general population. Risk of VTE did not differ between cohort-1 and general population (crude HR 0.98, 95%CI 0.90-1.06). Risk of VTE was greater in cohort-2 versus general population (crude HR 1.30, 95%CI 1.18–1.42). However, there was no difference in risk after adjusting for VTE risk factors (adjusted HR 0.97, 95%CI 0.87–1.08).

Conclusion: In this retrospective cohort study conducted within an administrative claims database, AD was not an independent risk factor for VTE and baseline risk of VTE among patients with AD was low. The apparent increased risk of VTE among patients with moderate-to-severe AD is explained in part by comorbidities and medications that are risk factors for VTE.

Financial Disclosures: This study was previously presented at EADV 2020.

The safety and efficacy of roflumilast cream 0.15% and 0.05% in atopic dermatitis: Phase II proof-of-concept study

Presenters: Gooderham M,¹ Kircik L,² Zirwas M,³ Lee M,⁴ Kempers SE,⁵ Draelos Z,⁶ Ferris LK,⁷ Jones TM,⁸ Saint-Cyr Proulx E,⁹ Bissonnette R,⁹ Bhatia N,¹⁰ Guenthner ST,¹¹ Koppel RA,¹² Welgus H,¹³ Merritt C,¹³ Elias M,¹³ Navale L,¹³ Higham RC,¹³ Droege M,¹ Berk DR¹³

Affiliations: ¹SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, Ontario, Canada; ²Icahn School of Medicine at Mount Sinai, New York, NY; Indiana Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY; ³Dermatologists of the Central States, Probity Medical Research and Ohio University, Bexley, OH; ⁴Progressive Clinical Research, San Antonio, TX; ⁵Minnesota Clinical Study Center, Fridley, MN; ⁶Dermatology Consulting Services, PLLC, High Point, NC; ⁷University of Pittsburgh, Department of Dermatology, Pittsburgh, PA; ⁸US Dermatology Partners, Bryan, TX; ⁹Innovaderm Research, Montreal, Quebec, Canada; ¹⁰Therapeutics Clinical Research, San Diego, CA; ¹¹The Dermatology Center of Indiana, PC; The Indiana Clinical Trials Center, PC, Plainfield, IN; ¹²Clinical Trials Management, LLC, Metairie, LA; Tulane University School of Medicine in New Orleans, LA; Arcutis Biotherapeutics, Inc., Westlake Village, CA

Background: Roflumilast cream (ARQ 151) is a highly potent phosphodiesterase-4 (PDE-4) inhibitor with ~25- to >300-fold higher potency than the approved PDE-4 inhibitors, crisaborole and apremilast. Roflumilast cream is in development for plaque psoriasis and AD.

Objective: The objective of this Phase II, proof-of-concept study was to assess the safety and efficacy of once daily roflumilast cream 0.15% and 0.05% in patients with mild-to-moderate AD.

Methods: This randomized, parallel-group, double-blind, vehicle controlled study enrolled 136 patients (? 12 years of age) from North America who had 1.5 to 35-percent BSA affected by AD, with a validated Investigator Global Assessment AD (vIGA-AD) score of 2 (mild) or 3 (moderate), and EASI score of five or more. Patients were randomized to roflumilast 0.15%, roflumilast 0.05% or vehicle once-daily for four weeks. The primary efficacy endpoint was absolute change from baseline in EASI score at Week 4.

Results: At baseline, 22.1 percent of patients had a vIGA-AD of mild, 77.9 percent had a vIGA AD of moderate, and mean BSA was 9.5 percent. At Week 4, the mean changes in EASI scores were 6.4 (P=0.097 compared with vehicle), 6.0 (P=0.356), and 4.8 with roflumilast 0.15%, roflumilast 0.05%, and vehicle, respectively (primary endpoint). Statistically significant improvements compared with vehicle were observed at Week 4 for percent change from baseline in EASI score (72.3% [P=0.049], 69.4% [P=0.164], and –55.8% for roflumilast 0.15%, roflumilast 0.05%, and vehicle, respectively); patients reaching EASI 75 (52.3% [P=0.045], 59.1% [P=0.009], and 31.1%); and patients achieving vIGA-AD score of clear or almost clear (52.3% [P=0.040], 50.0% [P=0.076], and 31.1%). Overall, four patients experienced a TEAE: none in roflumilast 0.15%, two in roflumilast 0.05%, and two in vehicle group. Only two patients discontinued study drug due to an AE. Application site pain was reported in two patients: one in roflumilast 0.05% and one in vehicle group.

Conclusion: In this small study, the primary endpoint showed a trend towards, but did not reach, statistical significance. However, statistical significance was reached for other efficacy endpoints. Both doses of roflumilast cream had a favorable safety profile, with a low rate of application site reactions. This study suggests that roflumilast cream, a potent PDE-4 inhibitor, represents a potential effective once-daily treatment for AD.

Tralokinumab provides progressive improvements beyond Week 16 in patients with atopic dermatitis with an initial partial response

Presenters: Simpson EL,¹ Thyssen JP,² Flohr C,³ Katoh N,⁴ Papp K,⁵ Steffensen LA,⁶ Bang B,⁶ Kuznetsova A,⁶ Blauvelt A⁷

Affiliations: ¹Department of Dermatology, Oregon Health & Science University, Portland, OR; ²Department of Dermatology and Allergy, Copenhagen University Hospital Herlev-Gentofte, Copenhagen, Denmark; ³St. John’s Institute of Dermatology, King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom; ⁴Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; ⁵Probity Medical Research, Waterloo, Ontario, Canada; ⁶LEO Pharma A/S, Ballerup, Denmark; ⁷Oregon Medical Research Center, Portland, OR

Background: In the Phase III ECZTRA 1 and 2 trials in adults with moderate-to-severe AD, tralokinumab monotherapy provided significant and early improvements in clinically relevant endpoints. In both trials, significantly more patients receiving tralokinumab monotherapy than placebo achieved the primary endpoints of Investigator Global Assessment of 0 or 1 (IGA 0/1) [clear or almost clear skin] and 75-percent improvement in EASI (EASI-75).

Methods: ECZTRA 1 and 2 were 52-week, multinational, randomized, placebo-controlled, double-blind trials of identical design. Adult patients with AD for one year or more were initially randomized 3:1 to tralokinumab 300mg or placebo Q2W for 16 weeks. Patients who achieved IGA 0/1 or EASI-75 with tralokinumab at Week 16 were re-randomized (2:2:1) to tralokinumab Q2W or Q4W, or placebo. Patients who did not achieve IGA 0/1 or EASI-75 transferred to open-label tralokinumab 300mg Q2W plus optional TCS for an additional 36 weeks. This post-hoc analysis of pooled data from both studies assessed clinical responses during open-label treatment in patients who did not achieve IGA 0/1 or EASI-75 at Week 16.

Results: In the pooled analysis, 686 of 1196 (57.4%) tralokinumab-treated patients (360 and 326 from ECZTRA 1 and 2, respectively) were transferred to open-label treatment. The proportion of patients achieving IGA 0/1 or EASI-75 at Week 52 with tralokinumab plus optional TCS was 20.1 percent and 42.9 percent, respectively. More than half of responder proportions at Week 52 were achieved within eight weeks of starting open-label treatment; 11.4 percent and 31.9 percent achieved IGA 0/1 and EASI-75 by Week 24 of the studies. In an alternative analysis, to understand if the increased response over time was due to the addition of optional TCS or to extended tralokinumab treatment alone, patients (49.3%) who used concomitant anti-inflammatory treatment (mainly TCS) were considered non-responders; the response rates were 13.9 percent and 25.7 percent for IGA 0/1 and EASI-75 at Week 52, respectively. When considering the level of AD disease activity at Week 16, 53.2 percent of the patients who had EASI-50 to -74 at Week 16 achieved EASI-75 at Week 52, and 36.5 percent of the patients who had IGA 2 at Week 16 achieved IGA 0/1 at Week 52. By contrast, 29.3 percent of the patients with EASI <25 at Week 16 achieved EASI-75 at Week 52, and 7.6 percent of patients with IGA 4 at Week 16 achieved IGA 0/1 at Week 52.

Conclusion: These data show that patients who did not achieve IGA 0/1 or EASI-75 at Week 16 improved progressively with continued tralokinumab treatment beyond Week 16. The clinical response with continued treatment beyond Week 16 was driven mainly by continued tralokinumab treatment and not by the addition of optional TCS. This suggests that a substantial proportion of patients not achieving success endpoints at Week 16 continues to experience further disease improvement with continued tralokinumab therapy over the course of 52 weeks.

Funding: The ECZTRA 1 and 2 studies were sponsored by LEO Pharma A/S.

CELLULITIS

Incidence and outcomes of imaging for cellulitis in hospitalized patients with active intravenous drug use

Presenters: Chand S,¹ Rrapi R,¹ Lam J,² Chakrala T,¹ Song S,¹ Yi Z,¹ Nguyen E,¹ Kroshinsky D¹

Affiliations: ¹Department of Dermatology, Massachusetts General Hospital, Boston, MA; ²Boston University Dermatology Residency, Boston University School of Medicine, Boston, MA

Background: Cellulitis is an infection of the skin and skin-associated structures that commonly affects patients with ongoing intravenous drug use due to repeated trauma to the skin barrier. Common complications, such as cutaneous abscess, can also occur and are typically detected by physical or radiologic examination. Published guidelines on indications for acquiring imaging in cellulitis are limited even though such complications may occur more frequently in vulnerable populations.

Objective: This study assessed the incidence and outcomes of imaging acquired for cellulitis in hospitalized patients with active intravenous drug use.

Methods: A retrospective chart review of adult patients treated for presumed cellulitis at Massachusetts General Hospital between 3/2016 and 11/2018 was conducted. Patients were identified using the Partners Research Patient Data Registry using the diagnosis codes for cellulitis. Patients were then excluded who were seen only in the emergency department, transferred from other hospitals, had intensive care unit stays, or had complicated infection sites including around burns, chronic wounds, surgical sites, structural defects such as amputations, or underlying hardware such as orthopedic implants and intravenous access lines.

Results: 788 patient records were reviewed, of which 288 patients (36.5%) were included in the study. Seventy-five patients (26.0%) had ongoing intravenous drug use at the time of admission. Comparison of these patients revealed that those with active drug use were significantly younger (p<0.001) and have histories of skin infection (p=0.0012) and chronic liver disease (p<0.001). Cellulitis in patients with active drug use was also significantly more likely to present in the upper extremities (p<0.001), yield methicillin-resistant Staphylococcus aureus on wound culture (p=0.030), be purulent (p=0.0070), and be complicated by cutaneous abscess (p<0.001).Radiologic evaluation was prevalent in both groups with plain radiography and ultrasonography significantly more frequently obtained for patients with active intravenous drug use (p=0.035, p<0.001, respectively). Cutaneous abscess was the only finding discovered on ultrasonography that led to change in management for patients with active intravenous drug use. The majority of these detected abscess occurred in the upper extremity (n=4/7). Contrastingly, the most common finding on plain radiography leading to a change in management were foreign bodies (i.e., retained syringes) incidentally detected in the upper extremities for two patients. Interestingly, computed tomography was significantly more likely (p<0.001) to result in a change in management for patients with active intravenous drug use with cutaneous abscess as the most common finding.

Conclusion: There might be an overutilization of radiographic evaluation in patients with active intravenous drug use given the rarity of findings that change management. This patient group more frequently underwent radiologic evaluation and were more likely to have infections complicated by cutaneous abscess. Computed tomography was significantly more likely to detect cutaneous abscess in these patients, perhaps warranting its use to aid in diagnosis and management especially in contrast to patients without active intravenous drug use. More research is needed to specify indications for imaging for cellulitis in this patient population given their risk factors and potential complications.

CUTANEOUS ONCOLOGY

Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): A case series

Presenters: Au J,¹ Kurley SJ,² Fitzgerald A,² Somani AK¹

Affiliations: ¹Indiana University School of Medicine, Indianapolis, IN; ²Castle Biosciences, Inc., Friendswood, TX

Background: While cutaneous squamous cell carcinoma (cSCC) has an overall favorable prognosis, a subset of patients will develop metastases and die from their disease. Due to the rising incidence, the overall deaths from cSCC approach or surpass that from melanoma. A prognostic 40-GEP test has recently been independently validated to improve stratification of metastatic risk in high-risk cSCC patients. The 40-GEP test classifies patients into three groups based on risk for regional and/or distant metastasis (Class 1, low risk; Class 2A, moderate risk; Class 2B, highest risk). National guidelines for high-risk cSCC patients are unclear on which specific patients warrant additional work-up and management. Thus, treatment of high-risk cSCC often relies on risk assessment based on individual risk factors weighted by physician judgment and experience

Case reports: Case 1 with a history of renal and liver transplantation and cSCC presented with a papule on his left temple that was previously treated with cryotherapy. It was diagnosed to be a poorly differentiated cSCC (BWH T2a, AJCC stage T1). Mohs micrographic surgery (MMS) was completed in four stages and subsequent analysis of the last layer of non-marginal tissue was positive for cSCC. This prompted a review of the marginal frozen sections which showed a small foci of cSCC. While the residual cSCC may have been removed with the standing cone, there was no histologic confirmation. The patient was informed but declined any further treatments. The patient was recurrence-free for four years (death due to unrelated causes) and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result. Case 2 with a history of liver transplantation and cSCC presented with a two-month history of an exophytic growth on his left temple. It was diagnosed to be a poorly differentiated cSCC (BWH T2a, AJCC stage T1) with subsequent removal with MMS in two stages one month later. The patient then noted another growth immediately inferior to the linear scar line, as well as one on the ipsilateral helical root three months later. The biopsy results were consistent with metastatic cSCC. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result.

Conclusion:We present two cases that highlight the utility of the 40-GEP test as an adjunct to enhance cSCC risk stratification. Each patient had the same initial BWH and AJCC staging, yet with distinctively different outcomes. Case 1 highlighted a biologically less aggressive tumor (with a retrospective 40-GEP Class 1 result) that did not recur despite incomplete surgical clearance. Case 2 highlighted a biologically aggressive tumor (with a retrospective 40-GEP Class 2B result) that developed regional metastasis despite clear surgical margins obtained through MMS. Adjuvant treatment might have been appropriate for this patient earlier in the disease course and may have altered his prognosis. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies.

MISCELLANEOUS

Approach to hospitalized patients with fever and rash: A retrospective analysis of clinicopathologic features

Presenters: Lee J,¹ Uh J,¹ Kim J,¹ Kim H,¹ Lee S,¹ Kim M,¹ Lee U¹

Affiliations: ¹Department of Dermatology, Sanggye Paik Hospital, Seoul, Korea

Background: Fever and rash are common manifestations in patients; however, assessing them can be challenging because of the wide range of differential diagnosis.

Objective: We aimed to obtain tips that could assist in differential diagnoses in patients with fever and rash through the analysis of clinical features and histological findings.

Methods: Medical records of hospitalized patients who had undergone skin biopsy and had fever and skin rash were examined from January 2010 to December 2019.

Results: The patients of the adverse drug reaction group were older (p=0.024), and they had underlying diseases (p<0.001), whole body rash (p=0.018), elevated ALT (p=0.027), and epidermal exocytosis (p=0.024). The autoimmune disease group was associated with longer total fever and rash duration (p=0.049, 0.037), leukocytosis (p=0.015), neutrophilia (p=0.006), and dyskeratotic keratinocytes in the stratum corneum (p<0.001). Infectious erythema group was associated with targetoid lesions (p=0.003) and epidermal atrophy (p=0.022)

Conclusion: Clinicians should examine patients with fever and rash, considering that there may be various causes. This can be assisted by skin exam, lab test and skin biopsy.

Phase II safety and efficacy of VP-102, a drug-device combination product containing cantharidin (0.7% w/v), for the treatment of external genital warts (CARE-1)

Presenters: Guenthner ST,¹ McFalda W,² Tate M,³ Eads K,¹d’Arnaud P,⁴ Rieger J,⁵ Glover D,⁵ Willson C,⁵ Rosen T,⁶ Olivadoti M⁵

Affiliations: ¹The Indiana Clinical Trials Center, Plainfield, IN; ²Clarkston Skin Research, ³DelRicht Research, Tulsa, OK; ⁴Instat Consulting Inc, Chatham, NJ; ⁵Verrica Pharmaceuticals Inc., West Chester, PA; ⁶Baylor College of Medicine, Houston, TX

Background: External genital warts (EGW) are caused by the human papilloma virus, which is spread through direct skin-to-skin contact. Approximately one percent of people in the US have genital warts. Cantharidin has been used to treat EGW for decades, however there are no FDA-approved cantharidin products and no reliable or controlled source of cantharidin available.

Objective: VP-102 is a drug-device combination product that contains cantharidin (0.7% w/v). The primary objective of this Phase II study was to determine the optimal exposure duration for treatment, as well as the safety and efficacy of VP-102 in the treatment of EGW compared to vehicle.

Methods: This Phase II, randomized, double-blind, vehicle-controlled trial included two parts (A and B). Participants in study Part A (dose regimen finding) were randomized in a 5:1 ratio to receive either a two-hour, six-hour, or 24-hour exposure duration of VP-102 or vehicle. Participants in Part B received VP-102 or vehicle in a 3:2 ratio with a six-hour or 24-hour exposure duration. Study drug application occurred to any existing EGW every 21±4 days until complete clearance, or a maximum of four applications. Study drug was applied and covered with 3M® Dermablend surgical tape and removed at the designated exposure group time. An end of treatment (EOT) visit occurred at Day 84. Efficacy was measured by the percentage of subjects with complete clearance of all baseline and new treatable EGW at EOT. Safety was measured by incidence of AEs including local skin reactions (LSRs). Data for Part A and B were pooled for each individual treatment and exposure duration for safety and efficacy outcomes.

Results: Subjects presented with a mean wart count of 8.2 with a range of 2 to 30 EGW at baseline. Approximately 50 percent of subjects had EGW for one year or longer; with approximately 23 percent of subjects having EGW for more than five years. Pooled results from the six-hour or 24-hour VP-102 treatment exposure groups showed 36.7 percent and 33.3 percent of subjects achieved complete clearance of all treatable EGW at Day 84 compared to 4.5% (P<0.05) and zero percent (P<0.01) of subjects treated with vehicle. AEs experienced by the VP-102 treated subjects were consistent with the pharmacodynamic action of cantharidin as a vesicant. These side effects were primarily mild-to-moderate. The most common side effects included application site vesicles, pain and erythema. No subjects discontinued from the study due to adverse events and there were no serious adverse events reported that were deemed related to treatment by the investigator.

Conclusion: Treatment of EGW with VP-102 resulted in statistically significantly higher complete clearance of all EGW at the end of study visit compared to vehicle. VP-102 was well-tolerated and safety outcomes were consistent with the pharmacokinetic action of cantharidin as a vesicant.

Financial Disclosures: Funding for the studies was provided by Verrica Pharmaceuticals Inc.

Plasma cell vulvitis: A systematic review

Presenters: Sattler SS,¹ Elsensohn AN,² Mauskar MM,³ Kraus CN⁴

Affiliations: ¹Albany Medical College, Albany, NY; ²University of California, San Diego, CA; Department of Dermatology, San Diego, CA; ³University of Texas Southwestern Medical Center, Dallas, TX; ⁴University of California, Irvine, Department of Dermatology, Irvine, CA

Background: Plasma cell vulvitis (PCV) is an uncommon inflammatory vulvar dermatosis that is often refractory to treatment. PCV is thought to exist on a spectrum of plasma cell mucositis, which can involve the oral mucosa and glans penis. The etiology of PCV is unknown, but autoimmunity has been proposed due to co-occurrence of PCV in patients with other autoimmune conditions.

Objective: The purpose of this review was to summarize the epidemiological, clinical, and histological findings, as well as identify associated comorbidities and treatment options for patients with this uncommon and often recalcitrant vulvar condition.

Methods: A primary literature search was conducted using PubMed, Ovid Medline, Cochrane, and CINAHL databases, generating primarily case reports and case series. Non-duplicate publications in the English language investigating PCV and reporting a case presentation were included in our analysis. Demographics, comorbidities, anatomical location, symptoms, clinical and histopathologic findings, and treatments were evaluated for all included cases.

Results: Fifty-three publications with 196 patients (mean age 55.3±14.5 years) diagnosed with PCV were included. No predominant ethnic distribution could be determined for this condition. Six cases (3%) of patients with autoimmune conditions coexisting with PCV were reported. While sometimes asymptomatic (5%), common symptoms associated with this condition include burning/stinging (52%), dyspareunia (44%), and pruritus (41%). Clinical findings consist of erythema (84%), glistening/shiny appearance (29%), well-demarcation (25%), and erosions (22%). Other descriptions mention a faint orange hue or lesions with “cayenne pepper” coloration. Common anatomic sites involve the labia minora (45%), introitus (31%), and periurethral area (19%). Lesions can be multiple or solitary (53%). Common histologic findings of PCV include a predominant plasma cell infiltrate (88%), presence of other inflammatory cells (55%), hemosiderin/siderophages (46%), and epidermal atrophy (43%). Basal keratinocyte crowding is a histological finding that, although less frequently reported, has been observed. Topical corticosteroids (64%) and tacrolimus (11%) were the most frequently reported treatment modalities. Other topical and systemic modalities, as well as procedure-based therapies, have been reported but evidence is limited.

Conclusion: PCV is likely under recognized and should be considered in patients with erythema of the mucous and modified mucous membranes, symptoms of burning or stinging, and a predominant plasma cell infiltrate on histopathology. Prospective studies are needed to develop treatment guidelines.

Topical treatments for pediatric toenail onychomycosis: Overview of efficacy in three clinical trials

Presenters: Scher R,¹ Vlahovic T,² Joseph W,³Gupta AK,^4,5 Lipner SR,¹ Eichenfield L,⁶ Rich P,⁷ Guenin E⁸

Affiliations: ¹Department of Dermatology, Weill Cornell Medicine, New York, NY; ²Temple University School of Podiatric Medicine, Philadelphia, PA; ³Arizona College of Podiatric Medicine, Midwestern University, Glendale, AZ ; ⁴Mediprobe Research Inc., London, Ontario, Canada; ⁵University of Toronto, Toronto, Ontario, Canada; ⁶Departments of Dermatology and Pediatrics, University of California, San Diego School of Medicine and Rady Children’s Hospital, San Diego, CA; ⁷Oregon Health and Science University, Portland, OR; ⁸Ortho Dermatologics, Bridgewater, NJ

Background: Pediatric onychomycosis prevalence may be increasing, with rates in North America rising from 0.44 percent to 1.1 percent. Treatments approved in the US for pediatric patients are the topicals efinaconazole 10 percent (approved for use in patients ? 6 years of age), tavaborole 5% (?6 years of age), and ciclopirox 8% (?12 years of age).

Objective: We summarize here published efficacy results from three clinical studies of these topical treatments in pediatric patients with toenail onychomycosis: efinaconazole (NCT02812771), tavaborole (NCT03405818), and ciclopirox (NCT01419847).

Methods: Two of the reviewed studies were open label (efinaconazole [n=60], tavaborole [n=54]) and one was randomized, double blinded, and vehicle controlled (ciclopirox [n=35]). Eligible participants were aged 6 to16 years old (efinaconazole, tavaborole) or 2 to 16 years (ciclopirox) with culture-positive onychomycosis affecting at least 20 percent of a target great toenail. Treatments were administered once daily for 48 weeks with a follow up at 52 weeks (efinaconazole, tavaborole) or for 32 weeks (ciclopirox). In the ciclopirox study, vehicle-treated participants with poor response (positive fungal culture at Week 8 or Investigator’s Global Assessment [IGA] score >three at Week 12) were crossed over to active drug at Week 12. Efficacy assessments included mycologic cure, negative fungal culture, complete cure, and complete/almost complete cure. Mycologic cure was defined as a negative potassium hydroxide and negative fungal culture (efinaconazole, tavaborole). Complete cure was defined as: zero percent clinical involvement (clear nail) and mycologic cure (efinaconazole, tavaborole); or IGA score of 0 (complete clearance) and negative fungal culture (ciclopirox). Complete/almost complete cure was defined as: five percent or less toenail involvement (clear/almost clear nail) and mycologic cure (efinaconazole, tavaborole). All data are presented descriptively.

Results: Mycologic cure rates were numerically higher with efinaconazole (65.0%) than with tavaborole (36.2%) at Week 52. In studies with a more stringent definition of complete cure that included mycologic cure, a numerically greater rate was observed with efinaconazole (40.0%) versus tavaborole (8.5%) at Week 52; in the ciclopirox study, where complete cure was limited to IGA and negative fungal culture, 34.2 percent of participants achieved complete cure at Week 32. A greater percentage of efinaconazole-treated participants also achieved complete/almost complete cure versus tavaborole at Week 52 (41.7% vs. 14.9%). In all three studies, a majority of participants achieved negative fungal culture (88.3% efinaconazole; 87.2% tavaborole; 77.1% ciclopirox).

Conclusion: Once-daily efinaconazole 10% was efficacious in pediatric patients with onychomycosis, with numerically higher rates of mycologic cure, complete cure, and complete/almost complete cure rates at 52 weeks compared with patients in a similarly designed tavaborole 5% study. Though direct comparisons cannot be made across studies, placing data from the efinaconazole and tavaborole studies into context with the ciclopirox study is particularly challenging given differences in study design and lack of standardization in how efficacy assessments were defined. Overall, these pediatric data align with a recent Cochrane review of treatments for adult onychomycosis, which found that high-quality evidence supports the effectiveness of efinaconazole for complete cure, moderate-quality evidence supports tavaborole, and low-quality evidence supports ciclopirox lacquer.

Disclosures: Ortho Dermatologics is a division of Bausch Health US, LLC. This abstract was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC.

RS has nothing to disclose. TV has served as investigator and speaker for Ortho Dermatologics. WJ has served as consultant and speaker for Ortho Dermatologics. AKG has served as consultant, speaker, and investigator for Ortho Dermatologics. SRL has nothing to disclose. LE has received honoraria for consulting services from Almirall, Celgene, Dermira, Dermavant, Eli Lilly, Forte Pharma, Galderma, Incyte, Otsuka, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Ortho Dermatologics; and study support (to institution) from Dermira, Eli Lilly and Company, Galderma, Incyte, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme.

PR has received research and educational grants from AbbVie, Allergan, Anacor Pharmaceuticals, Boehringer Ingelheim, Cassiopea, Dermira, Eli Lilly, Galderma, Janssen Ortho Inc., Kadmon Corporation, LEO Pharma, Merck, Moberg Derma, Novartis, Pfizer, Ranbaxy Laboratories Limited, Sandoz, Viamet Pharmaceutical Inc., Innovation Pharmaceuticals (Cellceutix), and Cutanea Life Sciences.

EG is an employee of Ortho Dermatologics and may hold stock and/or stock options in its parent company.

Variations in systemic disease and cardiovascular involvement in patients presenting with cutaneous sarcoid between racial groups

Presenters: Kassamali B,¹ Villa-Ruiz C,^1,2 Kus K,^1,3 Kassamali AA,¹ Gizelis O,¹ Vleugels RA,¹ LaChance A,¹ Imadojemu S¹

Affiliations: ¹Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; ²Ponce Health Sciences University, Ponce, Puerto Rico; ³Oakland University William Beaumont School of Medicine, Rochester, MI

Background: Sarcoidosis is a disease characterized by systemic granulomas with an unclear pathogenesis, but known higher incidence in Black patients than White. Since cutaneous manifestations are common in sarcoidosis, patients often present to dermatology for initial diagnosis. However, patients might already have unrecognized systemic organ involvement at the time of sarcoid diagnosis.

Objective: Although studies analyzing health disparities in epidemiology and prognosis of sarcoidosis exist, this is the first study to evaluate the racial differences in systemic involvement among patients initially presenting to dermatology with cutaneous sarcoidosis.

Methods: The Research Patient Data Registry, which combines medical records from two large, academic tertiary care centers in Boston, was utilized to identify 286 potential cases of cutaneous sarcoidosis between January 2000 and December 2019. Of these, 111 cases were confirmed through a retrospective chart review. This was further narrowed to include only cases that presented to Brigham and Women’s Hospital or Massachusetts General Hospital without established extracutaneous disease (n=50). From this cohort of 50 patients, data was extracted on whether the patient was found to have systemic disease after work-up following a diagnosis of cutaneous sarcoid. Statistical analysis was performed using the z-score test for two population proportions. P-values <0.05 were considered statistically significant.

Results: Among the 50 patients diagnosed with sarcoidosis based on presentation to dermatology for skin involvement, 24 were White, nine were Black, nine were Hispanic, and eight self-identified in other racial groups. 77.8 percent (7/9) of Black patients had systemic involvement at time of diagnosis of cutaneous sarcoid, compared to 46.3 percent (19/41) non-Black patients. Accordingly, Black patients had a 31.5 percent higher probability of having systemic involvement at time of presentation with cutaneous sarcoidosis (p<0.05). Of the Black patients who presented with cutaneous sarcoid without known extracutaneous disease, 33.3 percent were found to have disease in one extracutaneous organ and 44.4 percent were found to have disease in two or more organs. Of the patients who were non-Black and presented with cutaneous sarcoid without pre-established extracutaneous disease, 12.2 percent (5/41) of patients were found to have disease in one extracutaneous organ and 34.1 percent (14/41) showed disease in two or more organs. In terms of the scope of the organ involvement, of the non-Black patients found to have extracutaneous disease, zero percent (0/41) had cardiovascular involvement. In contrast, of the Black patients found to have extracutaneous disease, 28.6 percent (2/7) were found to have cardiovascular involvement.

Conclusion: Among patients who initially present with cutaneous sarcoidosis, the probability of being diagnosed with systemic disease is statistically significantly higher among Black patients than non-Black patients. Additionally, the probability of being found to have two or more organ manifestations on diagnosis is greater among Black patients than among non-Black patients. Furthermore, Black patients showed higher rates of cardiovascular organ involvement, which is associated with worse prognosis and substantial morbidity and mortality. Our data suggest there might be differences in the extent of organ involvement across racial categories in patients presenting with cutaneous sarcoidosis.

MOLLUSCUM CONTAGIOSUM

The hidden impact of molluscum contagiosum: Survey of caregivers’ experiences with diagnosis and management

Presenters: Kwong P,¹ Hebert A,² Utley C,³ Olivadoti M⁴

Affiliations: ¹Solutions Through Advanced Research, Jacksonville, FL; ²UTHealth McGovern Medical School, Houston, TX; ³Gold Skin Care Center, Nashville, TN; ⁴Verrica Pharmaceuticals Inc., West Chester, PA

Background: Molluscum contagiosum (molluscum) is a common pediatric viral skin infection. While this condition is considered benign and self-limiting, molluscum can last for months to years and cause itching and pain. The experience in caring for a child with molluscum largely remains a mystery, with few studies published on the topic. This online survey aimed to collect caregivers’ views on their experiences with molluscum infection in their children.

Methods: Parents, caregivers, and/or legal guardians of children (ages 3–16 years old) diagnosed with molluscum in the past four years were recruited to answer a 15-minute paid online survey. Survey questions inquired about the type of health care provider (HCP) consulted, diagnosis, treatment, and how severely molluscum impacted the caregiver and the child.

Results: Respondents (n=150) were mostly White (85%), between 25 and 44 years of age (87%), and had at least one child with an active infection (75%). Median household size was four people. The median age of children in the home was eight years. Most respondents saw at least two types of HCPs for their child’s molluscum. Diagnosis was completed by Pediatrics (49%), Family Practice (37%), Dermatology (34%), Infectious Disease (23%), and/or Emergency Room (21%). Spread of molluscum to one or more children in the household was reported in 60 percent of caregivers. Most caregivers were offered treatment options by the healthcare provider (61%) versus allowing the disease to remit on its own (39%). Most caregivers reported moderate to major impact on their lives (62%), 70 percent agreed with the statement that molluscum kept their child away from doing things they love, and 62 percent agreed they worried what others thought of their child having molluscum. Many respondents (47%) considered squeezing or removing lesions themselves at home and 31 percent utilized this strategy. The most common approaches to treatment were home remedies (43%) and molluscum treatments purchased from Amazon.com or a drug store with no Rx required (41%), followed by cryosurgery (41%), cantharidin (39%), and curettage (31%). The average number of treatments used was 2.36.

Conclusion: Results indicate that molluscum patients receive diagnoses from many HCP types, often visiting more than one HCP. Many patients do not receive treatment, and those that do receive treatment are likely to use more than one modality in attempt to clear the infection. Caregivers were likely to attempt to try at-home remedies or use unproven/unapproved remedies, as well as attempt to disrupt lesions themselves, creating opportunities for autoinoculation and spread of the infection. Not surprisingly, spread to another child in the household was common. Finally, a moderate to high impact on quality of life for caregivers and an impact on activities for their children with molluscum was reported. This suggests that while physically benign, molluscum has an emotional impact patients and their caregivers, with concern over a negative social stigma.

Financial Disclosures: Funding for this survey was provided by Verrica Pharmaceuticals Inc., in conjunction with Whitman Insight Strategies.

PRURITUS

A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine ER tablets for uremic pruritus

Presenters: Mathur VS,¹ Sciascia T²

Affiliations: ¹MathurConsulting, Woodside, CA; ²Trevi Therapeutics, New Haven, CT

Background: Pruritus is a distressing hallmark of the uremic condition. Despite modern day dialytic management, 60 percent of dialysis patients experience itching and approximately 30 to 45 percent experience moderate or severe/extreme pruritus. Abnormal endogenous opioid ligand activity at ?– and ?-opioid receptors has been postulated as a mechanism in uremic pruritus; specifically, ?-opioid agonism and ?-opioid antagonism reduce scratching behavior in animal models. Nalbuphine (a synthetic, dual-acting ? antagonist and ? agonist) has been shown to reduce morphine-related pruritus.

Objective: We sought to evaluate safety and antipruritic efficacy of oral nalbuphine extended release (NAL-ER) tablets in hemodialysis patients with uremic pruritis.

Methods: In this Phase II/III, multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1:1:1 ratio to nalbuphine extended-release tablets 108mg (NAL 108), 54mg (NAL 54), or placebo (PBO) and treated for eight weeks and then followed for two weeks posttreatment. Patients with pruritus related to other conditions (e.g., hepatic, malignancy, primary dermatologic condition) were excluded. The primary endpoint was the comparison between NAL 108 versus placebo at Weeks 7–8 (Evaluation Period) on itching intensity using a Worst Itching Intensity Numerical Rating Scale (NRS, 0 [no itching] – 10 [worst possible itching]). Quality of life-related secondary endpoints included change from Day 1 to the Evaluation Period in itching-related quality of life and itching-related sleep disruption.

Results: Three hundred seventy-one patients were analyzed for efficacy. In the NAL 108, NAL 54, and PBO groups, 65 percent, 58 percent, and 81 percent completed the eight-week treatment, respectively. From a baseline NRS (SD) of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) in the NAL108 group, representing a 49 percent reduction in itch intensity, and by 2.8 (2.2) in the PBO group (p=0.017). Significant itch reduction was evident in the NAL 108 group as early as Week 3. There was no evidence of tolerance or rebound. A trend for less sleep disruption due to itching (p=0.062, NAL 108 vs. PBO) was also observed. There were no significant differences between NAL 54 versus PBO. The most common reason for discontinuing treatment in the active groups was opioid-type side effects (e.g., nausea and vomiting) that occurred during the forced titration period. One death occurred in the placebo group. The incidence of serious treatment-associated adverse events was 6.7 percent, 12.7 percent, and 15.4 percent in the NAL 108mg, NAL 54 mg, and PBO groups respectively.

Conclusion:In this large randomized, controlled trial in uremic pruritus, NAL 108 durably and significantly reduced the itching intensity among hemodialysis patients.

Disclosures: Funding toward this study was received from Trevi Therapeutics. Previous publications used the molecular weight including salts, whereas this abstract uses the current FDA recommendations to use the molecular weight of just the active drug.

Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: Results of a Phase II randomized controlled trial with an open-label extension phase

Presenters: Weisshaar E,¹ Sciascia T,² Ständer S³

Affiliations: ¹University Hospital, Heidelberg, Germany; ²Trevi Therapeutics, New Haven, CT; ³University Hospital, Münster, Germany

Background: Prurigo nodularis (PN) is a relatively rare, intensely pruritic dermatologic disease that develops from prolonged itching and scratching, with a high associated quality of life (QoL) impact. Treatment of PN remains challenging. Therapies such as calcineurin inhibitors, topical steroids, and systemic antihistamines have limited data to support their use. The synthetic opioid nalbuphine, a dual-acting ? antagonist and ? agonist, has shown efficacy in morphine-induced pruritus and uremic pruritus, but an evaluation of the efficacy and safety of nalbuphine in PN is currently lacking.

Objective: We sought to evaluate efficacy and safety of oral nalbuphine extended release (NAL-ER) tablets for the treatment of prurigo nodularis in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial.

Methods: Patients with moderate-to-severe PN (pruritus duration ?6 weeks) were randomized 1:1:1 to receive either NAL-ER 81 mg (NAL-ER 81) or 162mg (NAL-ER 162) tablets twice-daily, or placebo for eight weeks of stable dosing following a two-week titration period (for dose-escalation from 30mg once-daily to the assigned target dose). Itch scores based on Worst Itch (WI) and average itch Numerical Rating Scale (NRS) with 24-hour recall were collected daily by electronic diary (DIARYpro®). The primary efficacy endpoint was the proportion of patients with a 30 percent or greater reduction in seven-day mean WI-NRS from baseline to Week 10 for patients who completed double-blind treatment. The primary safety endpoint was the incidences of opioid type adverse events of nausea, vomiting, constipation, somnolence, sedation, dizziness, and vertigo in each treatment group.

Results: Of 62 treated patients, 50 completed 10 weeks’ treatment. The primary efficacy endpoint of percentage of responders with 30 percent or greater reduction from baseline in seven-day WI intensity was not significant for the primary modified intent-to-treat analysis but was significant for NAL-ER 162 (75.0%) compared to placebo (40.0%; p=0.026) among completers. TEAEs occurred predominantly during the titration period in both studies. During double-blind, stable-dose treatment that followed titration, TEAE incidence was similar for both active treatment arms and placebo. Common TEAEs were nausea, dizziness, headache and fatigue; the majority of these events were also considered treatment-related in all three arms. In the extension study, 34 patients reported 154 TEAEs, including 26 patients with one or more drug-related TEAE. TEAEs included nausea (n=9; 25.0%), and dizziness and fatigue (n=8 for each; 22.2%).

Conclusion: Results provide preliminary evidence for the efficacy of NAL-ER tablets in the treatment of PN.

Financial Disclosures: Funding toward this study was received from Trevi Therapeutics.

The role of kappa and mu opioid receptors in pruritus

Presenters: Kim B,¹ Sciascia T,² Yosipovitch G³

Affiliations: ¹Washington University, St. Louis, MO; ²Trevi Therapeutics, New Haven, CT; ³University of Miami, Miami, FL

Background: Itch perception is transmitted from sensory neurons innervating the skin to the spinal cord. From there, spinal projection neurons relay signals to the brain, where itch sensation is perceived. A multitude of itch-inducing stimuli or pruritogens can trigger itch, including neurotransmitters, neuropeptides, proteases, and cytokines. However, pathways that suppress itch remain poorly understood. Recent studies have shed light on the emerging role of opioid receptors, particularly kappa-opioid receptors (KORs) and mu-opioid receptors (MORs), respectively, in suppressing and eliciting itch both in the periphery and more centrally.

Objective: Herein, we present a summary of recent work supporting the role of KORs and MORs as potential therapeutic targets in the treatment of itch.

Methods: A literature search of the PubMed database was conducted to identify English-language publications examining the role of opioid receptors in pruritus in the past decade; search terms included “opioid receptor”, “kappa”, “mu”, “pruritus”, and “itch”. Findings from relevant publications were summarized as a narrative review.

Results: KORs and MORs are expressed throughout both the peripheral and central nervous system. Imbalances of activity across the KOR and MOR systems in the skin or CNS are associated with severe chronic pruritus, and are an active area of research for novel treatments. Whereas activation of KORs results in attenuation of itch in a variety of contexts, activation of MORs is associated with increased itch. The inhibitory effects of KOR agonism are specific to itch. In addition, there are reports of KOR agonism resulting in suppression of inflammation. In contrast to MORs, activation of KORs has not been associated with addiction, which has important therapeutic implications given concerns about opioid use. Attenuation of itch has been demonstrated by KOR agonists, including the endogenous ligand dynorphin and drugs such as nalfurafine and difelikefalin, as well as by MOR antagonists such as naltrexone. Both KOR and MOR pathways are targeted with use of dual KOR agonist/MOR antagonists such as butorphanol and nalbuphine.

Conclusion: KORs and MORs have emerged as important therapeutic targets in itch. Notwithstanding these advances, the precise mechanisms by which KOR agonists and/or MOR antagonists can be employed therapeutically remains an exciting area worthy of further investigation.

PSORIASIS

Bimekizumab efficacy and safety versus adalimumab in patients with moderate-to-severe plaque psoriasis: Results from a multicenter, randomized, double-blinded active comparator-controlled Phase III trial (BE SURE)

Presenters: Warren RB,¹ Blauvelt A,² Bagel J,³ Papp K,⁴ Yamauchi P,^5,6 Armstrong A,⁷ Langley R,⁸ Vanvoorden V,⁹ Peterson L,¹⁰ De Cuyper D,⁹ Cross N,¹⁰ Reich K¹¹

Affiliations: ¹Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR BRC, The University of Manchester, Manchester, United Kingdom; ²Oregon Medical Research Center, Portland, OR; ³Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; ⁴Probity Medical Research and K Papp Clinical Research, Waterloo, Canada; ⁵Dermatology Institute and Skin Care Center, Santa Monica, CA; ⁶David Geffen School of Medicine at University of California, Los Angeles, CA; ⁷Keck School of Medicine of USC, Dermatology, Los Angeles, CA; ⁸Dalhousie University, Halifax, Canada; ⁹UCB Pharma, Brussels, Belgium; ¹⁰UCB Pharma, Raleigh, NC; ¹¹University Medical Center Hamburg-Eppendorf and Skinflammation® Center, Hamburg, Germany

Background: Psoriasis is the archetypal Th17-driven disease, with IL-17A and IL-17F pivotal in its pathogenesis. Bimekizumab (BKZ), a monoclonal IgG1 antibody, selectively inhibits IL-17F in addition to IL-17A.

Objective: This study evaluates the efficacy and safety of BKZ versus adalimumab (ADA) in patients with moderate-to-severe plaque psoriasis.

Methods: In BE SURE (NCT03412747) patients were randomized 1:1:1 to BKZ 320mg every four weeks (Q4W) for 56 weeks, BKZ 320mg Q4W for 16 weeks followed by BKZ 320mg every eight weeks (Q8W) to Week 56, or ADA 40mg every two weeks (Q2W) for 24 weeks, followed by BKZ 320mg Q4W to Week 56. Coprimary endpoints were PASI90 and IGA0/1 versus ADA at Week 16. Secondary endpoints included PASI90 and IGA0/1 at Weeks 24 and 56 and PASI100 at Weeks 16 and 24. Missing data were imputed using non-responder imputation. TEAEs were coded using MedDRAv19.0.

Results: 158, 161, and 159 patients were randomized to BKZ 320mg Q4W, BKZ 320mg Q4W/Q8W, and ADA 40mg Q2W/BKZ 320mg Q4W. Baseline demographics and characteristics were comparable between groups. All primary and ranked secondary endpoints were achieved. At Week 16, PASI90/IGA0/1/PASI100 were achieved by significantly more BKZ- than ADA-treated patients (PASI90: 86.2% vs. 47.2%, IGA0/1: 85.3% vs. 57.2%, PASI100: 60.8% vs. 23.9%; all p<0.001). Responses within BKZ treatment arms were durable through Week 56. In ADA-randomized patients, PASI90/PASI100/IGA0/1 responder rates rapidly increased following switch to BKZ 320mg Q4W at Week 24 and were comparable to Wk0-randomized BKZ patients at Week 56. Through Weeks 0–24, TEAEs/serious TEAEs were comparable for BKZ- and ADA-treated patients (TEAEs: 71.5% vs. 69.8%; serious TEAEs: 1.6% vs. 3.1%). Through Weeks 0–56, TEAEs=81.4% and serious TEAEs=5.1% (BKZ-treated patients, including ADA switchers). No deaths were reported in BKZ-treated patients; one occurred in an ADA-treated patient (Investigator-assessed as non treatment related). Over 56 weeks, there were no cases of suicidal ideation or behavior, inflammatory bowel disease, or major adverse cardiac events in BKZ treated patients. The most common TEAEs were nasopharyngitis (20.9%), oral candidiasis (16.2%), and upper respiratory tract infection (9.0%).

Conclusion: Superior, durable skin clearance was observed with BKZ versus ADA. Switching from ADA to BKZ rapidly increased PASI90/PASI100/IGA0/1 responder rates. BKZ was generally well tolerated; TEAEs were comparable with previous studies.

Funding: Funding came from UCB Pharma.

Disclosures: RBW has received research grants and/or consulting fees from AbbVie, Almirall, Amgen, Arena, Avillion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma. AB is a scientific adviser and/or clinical study investigator for AbbVie, Allergan, Almirall, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Forte, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma and UCB Pharma; paid speaker for AbbVie. JB is a speaker, investigator and/or consultant for AbbVie, Celgene, Eli Lilly, Leo Pharma, Novartis and Ortho Dermatologics. KAP has honoraria and/or grants from AbbVie, Akros, Amgen, Arcutis, Astellas, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Canfite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Gilead, GSK, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck (MSD), Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB Pharma, and Valeant/Bausch Health; consultant (no compensation) for AstraZeneca and Meiji Seika Pharma. PY is a speaker, investigator, consultant for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Ortho Dermatologics, Sun Pharma and UCB Pharma. AWA is a research investigator and/or consultant for AbbVie, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, Janssen, LEO Pharma, Kyowa Kirin, Modernizing Medicine, Novartis, Ortho Dermatologics, Regeneron, Sanofi, Sun Pharma and UCB Pharma. RL has honoraria from AbbVie, Amgen, Boeringer Ingelheim, Centocor, Eli Lilly, Janssen, LEO Pharma, Pfizer and Valeant/Bausch Health. VV, LP, DDC, and NC are employees of UCB Pharma. KR served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Covagen, Dermira, Eli Lilly, Forward Pharma, Fresenius Medical Care, Galapagos, GSK, Janssen, Kyowa Kirin, LEO Pharma, Medac, MSD, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB Pharma, Valeant/Bausch Health, and Xenoport.

**Bimekizumab for the treatment of moderate-to-severe plaque psoriasis with scalp, nail and palmoplantar involvement through 52 weeks: Post-hoc analysis from the BE VIVID Phase III trial**

Presenters: Papp K,¹ Lebwohl M,² Gottlieb AB,² Sebastian M,³ Langley R,⁴ Okubo Y,⁵ Wang M,⁶ Cioffi C,⁶ Staelens F,⁷ Reich K⁸

Affiliations: ¹Probity Medical Research and K Papp Clinical Research, Waterloo, Canada; ²Icahn School of Medicine at Mount Sinai, New York, NY; ³Dermatological Practice Dr. med. Michael Sebastian, Mahlow, Germany; ⁴Dalhousie University, Halifax, Canada; ⁵Tokyo Medical University, Tokyo, Japan; ⁶UCB Pharma, Raleigh, NC; ⁷UCB Pharma, Braine-l’Alleud, Belgium; ⁸University Medical Center Hamburg-Eppendorf and Skinflammation® Center, Hamburg, Germany

Background: Psoriasis is the archetypal Th17-driven disease, for which IL-17A and IL-17F have emerged as pivotal drivers of inflammation. Bimekizumab (BKZ), a monoclonal IgG1 antibody, selectively inhibits IL-17F in addition to IL-17A. Scalp, nail and palmoplantar psoriasis cause significant physical impairment and negatively impact quality of life; management of psoriasis in these regions is challenging for physicians and patients.

Objective: We present scalp, nail and palmoplantar outcomes from a Phase III trial of BKZ in moderate-to-severe plaque psoriasis (PSO).

Methods: Adult patients were enrolled in the multicenter, randomized, double-blinded, placebo (PBO)- and active comparator-controlled Phase III study BE VIVID (NCT03370133); patients who developed psoriasis types other than plaque were excluded or withdrawn. Patients were randomized 4:2:1 to BKZ 320mg every four weeks (Q4W), ustekinumab (UST) 45mg/90mg (weight-based), or PBO (switching to BKZ 320mg Q4W at Week 16). The post-hoc analyses reported here include patient subsets with regional PSO involvement at baseline: scalp Investigator’s Global Assessment (IGA) ? three, modified Nail Psoriasis Severity Index (mNAPSI)>10, or palmoplantar (pp)-IGA ? 3. Scalp IGA and pp-IGA were measured on a five-point scale (0–4); mNAPSI was a total fingernail score on a 0–130 scale. Proportions of patients achieving complete clearance in each region (scalp IGA0, pp-IGA0, mNAPSI0) are reported to Week 52, with missing data imputed using non-responder imputation.

Results: At baseline, 321, 163, and 83 patients were randomized to BKZ, UST, and PBO, respectively. 235 (73%), 114 (70%), and 62 (75%) had scalp IGA ?three; 113 (35%), 62 (38%), and 30 (36%) had mNAPSI>10; 61 (19%), 28 (17%), and 14 (17%) had pp-IGA ? three, respectively. Among patients with baseline scalp IGA/pp-IGA ? three, higher proportions of BKZ- than UST-/PBO-treated patients achieved scalp IGA0/pp-IGA0 at Wk16. Responder rates were durable in all treatment arms: at Week 52, 71.9 percent/80.3 percent of BKZ-treated patients achieved scalp IGA0/pp-IGA0, respectively, versus 51.8 percent and 67.9 percent of UST-treated patients. Among BKZ-treated patients with baseline mNAPSI>10, the proportion achieving mNAPSI0 increased throughout. At Week 52, 54.0 percent of BKZ-treated patients achieved mNAPSI0, versus 30.6 percent treated with UST.

Conclusion: Complete clearance of scalp, nail and palmoplantar psoriasis was observed in a higher proportion of BKZ-treated patients than UST-/PBO-treated patients after 16 weeks. Initial responses were durable through Week 52 for BKZ-treated patients with scalp and palmoplantar symptoms, and increased for those with nail symptoms, reflecting the longer timescale required for nail growth. BKZ demonstrates high efficacy in high-impact areas in patients with moderate to severe PSO.

Financial Disclosures: Funding was provided by UCB Pharma.

Bimekizumab versus ustekinumab efficacy across subgroups of patients with moderate-to-severe plaque psoriasis: Results from the multicenter, randomized, double-blinded Phase III BE VIVID trial

Presenters: Strober B,^1,2 Krueger JG,³ Magnolo N,⁴ Vender R,⁵ Toth D,⁶ Thaçi D,⁷ Wang M,⁸ Cioffi C,⁸ Madden C,⁸ Warren RB⁹

Affiliations: ¹Yale University, New Haven, CT; ²Central Connecticut Dermatology Research, Cromwell, CT; ³The Rockefeller University, New York, NY; ⁴Universitätsklinikum Münster, Münster, Germany; ⁵McMaster University, Hamilton, Ontario, Canada; ⁶Probity Medical Research, Windsor, Ontario, Canada; ⁷Hospital of Lübeck, Lübeck, Germany; ⁸UCB Pharma, Raleigh, NC; ⁹Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR BRC, The University of Manchester, Manchester, United Kingdom

Background: Psoriasis is a Th17-driven disease, with increasing evidence that both IL-17A and IL-17F play a pivotal role in its pathogenesis. Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. Risk of psoriasis can vary by patient age, weight, prior treatment exposure, and other factors.

Objective: We assess efficacy of BKZ compared with ustekinumab (UST) over 52 weeks across subgroups of patients with moderate to severe plaque psoriasis (PSO).

Methods: BE VIVID (NCT03370133) was a Phase III, randomized, double-blinded, placebo- and active comparator-controlled trial in which patients were randomized 4:2:1 to BKZ 320mg every for weeks (Q4W) through Week 52, UST 45mg/90mg (weight-based) every 12 weeks through Week 52, or placebo. Placebo-randomized patients switched treatment at Week 16 to receive BKZ 320mg Q4W through Week 52. Randomization was stratified by prior biologic exposure and region. Post-hoc analyses of the following subgroups were conducted: baseline weight (kg; ?100, >100); prior biologic exposure (yes, no); prior anti-tumor necrosis factor exposure; prior anti-IL-17 exposure; prior anti-IL-23 exposure; age (years; <40, 40–<65, ? 65); PSO disease duration (<median [14.54 years] or ? median); baseline disease severity (absolute Psoriasis Area and Severity Index [PASI]; <20 or ? 20); and baseline Investigator’s Global Assessment (IGA; 3 or 4). Proportions of BKZ- versus UST-treated patients achieving PASI100 were calculated at Weeks 16 and 52. Missing data were imputed as non-response.

Results: Baseline characteristics were generally similar between BKZ (N=321) and UST (N=163) treatment arms: baseline mean PASI was 22.0 and 21.3, and mean BSA affected was 29.0 percent and 27.3 percent, respectively. At Weeks 16 and 52 respectively, 58.6 percent and 64.5 percent of BKZ-randomized patients and 20.9 percent and 38.0 percent of UST-randomized patients achieved PASI100. High levels of PASI100 response to BKZ were seen across all subgroups at both Week 16 and Week 52. The proportion of patients achieving PASI100 was greater for BKZ- than UST-randomized patients across reported subgroups at Week 16, ranging from 44.1 to 63.6 percent for BKZ and 0.0 to 29.2 percent for UST. Among BKZ-treated patients, 60.2 percent weighing ? 100kg and 54.7% weighing >100kg achieved PASI100 at Week 16, as did 60.8 percent with prior biologic exposure and 57.1 percent without. Week 16 responses further improved to Week 52, ranging from 50.0–69 percent for BKZ and 16.7–50.9 percent for UST.

Conclusion: BKZ provided robust and durable complete skin clearance in patients with PSO through 52 weeks, as demonstrated by higher PASI100 responses compared with UST, regardless of baseline demographics, disease characteristics, or prior treatment exposure.

Financial Disclosures: Funding was provided by UCB Pharma.

Disclosures: BS is a Consultant (honoraria) from AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Equillium, GSK, Janssen, LEO Pharma, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma and UCB Pharma; speaker for AbbVie, Amgen, Eli Lilly, Janssen and Ortho Dermatologics; Scientific Director (consulting fee) for Corrona Psoriasis Registry; Investigator for AbbVie, Cara, Corrona Psoriasis Registry, Dermavant, Dermira and Novartis; Editor-in-Chief (honorarium) for Journal of Psoriasis and Psoriatic Arthritis.

JGK has grants paid to institution from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen MA, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Eli Lilly, Exicure, Incyte, Innovaderm, Janssen, LEO Pharma, Novan, Novartis, Paraxel, Pfizer, Regeneron, Sienna, UCB Pharma and Vitae; personal fees from AbbVie, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigne, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Escalier, LEO Pharma, Nimbus, Novartis, Menlo, Pfizer, Sanofi, Sienna, Sun Pharma, UCB Pharma and Valeant.

NM is an honoraria, advisor, and/or paid speaker for and/or participated as principal investigator in clinical trials for AbbVie, Almirall, Asana, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene Corporation, Dermira, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Incyte, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma and UCB Pharma.

RV is a consultant, and/or scientific advisor, and/or investigator, and/or speaker for AbbVie, Amgen, Astellas, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck (MSD), Merck Serono, Novartis, Pfzer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda and UCB Pharma.

DPT is an investigator and/or speaker for AbbVie, Amgen, Arcutis, Avillion, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Merck-Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Sun Pharma and UCB Pharma.

DT has honoraria for participation on advisory boards, as a speaker and for consultancy from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Biopharma, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz-Hexal, Sanofi and UCB Pharma; Research grants received from Celgene and Novartis.

MW is an employee of UCB Pharma. CC and CM are employees and shareholders of UCB Pharma.

RBW has research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer and UCB Pharma; Consultant for AbbVie, Almirall, Amgen, Arena, Avillion, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma.

Bimekizumab versus ustekinumab in plaque psoriasis: Lasting efficacy translates to rapid and sustained improvements in quality of life in the BE VIVID multicenter, randomized, double-blinded Phase III trial

Presenters: Gordon K,¹ Foley P,² Rich P,³ Duffin K,⁴ Pinter A,⁵ Griffiths CEM,⁶ Wang M,⁷ Vanvoorden V,⁸ Staelens F,⁹ Ciaravino V,¹⁰ Merola JF¹¹

Affiliations: ¹Medical College of Wisconsin, Milwaukee, WI; ²The University of Melbourne, St. Vincent’s Hospital Melbourne, Fitzroy and Probity Medical Research Inc., Skin Health Institute, Carlton, Australia; ³Oregon Dermatology and Research Center, Portland, OR; ⁴University of Utah, Salt Lake City, UT; ⁵University Hospital Frankfurt, Frankfurt am Main, Germany; ⁶The University of Manchester, Manchester, United Kingdom; ⁷UCB Pharma, Raleigh, NC; ⁸UCB Pharma, Brussels, Belgium; ⁹UCB Pharma, Braine-l’Alleud, Belgium; ¹⁰UCB Pharma, Colombes, France; ¹¹Harvard Medical School, Brigham and Women’s Hospital, Boston, MA

Background: The disease burden of psoriasis can have a profound negative impact on quality of life (QoL), extending beyond physical manifestations. Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, both of which are pivotal in psoriasis immunopathogenesis.

Objective: We examine how absolute Psoriasis Area and Severity Index (PASI), a measure of psoriasis disease control, translates to improvements in Dermatology Life Quality Index (DLQI) in patients with moderate-to-severe plaque psoriasis (PSO) receiving BKZ versus ustekinumab (UST) and placebo (PBO).

Methods: The BE VIVID (NCT03370133) Phase III, double-blinded, PBO- and active comparator-controlled trial randomized patients 4:2:1 to BKZ 320mg every four weeks (weeks; Q4W) through Week 52, UST 45mg/90mg (weight-based) every 12 weeks through Week 52, or PBO (switching to BKZ 320mg Q4W at Week 16 through Week 52). PSO was assessed by PASI; PASI=0 indicated complete skin clearance and PASI of two or more, a relevant PSO disease endpoint for a treat to target approach, indicated disease control. Patients completed the DLQI questionnaire throughout treatment; DLQI0/1 indicated no impact on QoL. To evaluate the possible relationship between clinical response and impact on health-related QoL, patients achieving DLQI0/1 were grouped by PASI=0, PASI ? 2, 2<PASI<5, and PASI ? 5. Weeks 4/16 data for all patients, and Week 52 data for BKZ- and UST-randomized patients, are presented. Data are presented as observed cases (OC).

Results: There were 567 patients randomized to BKZ (n=321), UST (n=163), or PBO (n=83). A greater proportion of BKZ-treated patients rapidly achieved PASI=0 (15.1% vs. 1.2% [UST] and 2.5% [PBO]) and PASI ? 2 (46.5% vs. 6.2% [UST] and 2.5% [PBO]) at Week 4 (OC). This was further improved and sustained through Week 16 to Week 52. Rapid improvements in DLQI were seen with BKZ: 37.5 percent achieved DLQI0/1 by Week 4 versus 11.2 percent (UST) and 6.3 percent (PBO), improving to Week 52 (86.6% vs. 73.0% [UST]). Across treatment arms, higher disease control translated to greater QoL. This was most pronounced in BKZ, with 65.1% percent/83.8 percent of patients achieving both PASI ? 2 and DLQI0/1 at Weeks 16/52, versis 34.6 percent/59.7 percent for UST (OC).

Conclusion: Greater proportions of BKZ- than UST-treated patients quickly achieved higher disease control and lasting complete skin clearance after one year of treatment, translating to substantial, durable improvements in DLQI. Most BKZ-treated patients achieved PASI? 2 and DLQI0/1 at Week 52.

Financial Disclosures: Funding was provided by UCB Pharma.

Disclosures: KG: Honoraria and/or research support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma.

PF has grant support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; Investigator for AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Galderma, Genentech, Geneseq, GSK, Hexima, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi Genzyme, Sun Pharma, UCB Pharma, and Valeant/Bausch Health; served on the advisory board for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, UCB Pharma, and Valeant/Bausch Health; consultant for Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, and Wintermute; received travel grants from AbbVie, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, and Sanofi; speaker for or received honoraria from AbbVie, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, and Roche.

PR has research grants due to being principal investigator from AbbVie, Arcutis, Bristol Myers Squibb, Centocor, Dermavant, Eli Lilly, Kadmon, Merck, Novartis, Pfizer, Sun Pharma, and UCB Pharma.

KD received grants/investigator for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, Sienna, Stiefel, and UCB Pharma; Speaker’s Bureau for Novartis (non-promotional only); consultant/advisory board for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Ortho Dermatologic, Pfizer, Sienna, Stiefel, and UCB Pharma.

AP is an investigator and/or speaker and/or advisor for AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi Pharma, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, Schering-Plough, Tigercat Pharma, and UCB Pharma.

CEMG has onoraria and/or grants from AbbVie, Almirall, BMS, Celgene, Eli Lilly, Galderma, LEO Pharma, Janssen, Novartis, Pfizer, Sandoz, and UCB Pharma.

MW, VV, FS, and employees of UCB Pharma.

FM is a consultant and/or investigator for AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, EMD-Serono, Janssen, LEO Pharma, Merck, Novartis, Regeneron, Sanofi, Sun Pharma, Pfizer, and UCB Pharma.

Calcipotriene and betamethasone dipropionate cream combines high efficacy, favorable safety, and treatment preference in a single product for topical treatment of psoriasis

Presenters: Stein Gold L,¹ Green LJ,² Dhawan S,³ Præstegaard M,⁴ Selmer J⁴

Affiliations: ¹Dermatology Clinical Research, Henry Ford Health System, Detroit, MI; ²George Washington University School of Medicine, Washington, DC; ³Center for Dermatology Clinical Research, Fremont, CA, and Stanford University School of Medicine, Stanford, CA; ⁴MC2 Therapeutics, Hørsholm, Denmark

Background: Plaque psoriasis is a chronic inflammatory disease that affects approximately three percent of the population. Effective topical treatments for psoriasis should display high efficacy, with optimal delivery of actives to target tissue, exhibit a favorable safety and tolerability profile, and be associated with desirable patient preferences. Calcipotriene and betamethasone dipropionate (CAL-BDP; 0.005%/0.064% w/w) cream is a novel FDA-approved topical treatment of plaque psoriasis under the brand name Wynzora® Cream. CAL/BDP cream is based on PAD™ Technology, which has enabled development of a water-containing formulation of CAL and BDP, despite their known pH-related instability when combined in the presence of water. The clinical profile of CAL/BDP cream is in accordance with the recommendations in the guidelines of care for topical treatment of psoriasis issued by the American Academy of Dermatology and the National Psoriasis Foundation.

Objective: The objective of this presentation is to characterize the efficacy and safety of CAL/BDP cream compared to CAL/BDP topical suspension (CAL/BDP TS; Taclonex® Topical Suspension).

Methods: CAL/BDP cream was evaluated in a head-to-head, Phase III, randomized, multicenter, investigator-blind, parallel-group trial comparing the efficacy and safety of CAL/BDP cream to vehicle and CAL/BDP TS in adults with psoriasis vulgaris (NCT03308799). Eligible participants were adults (? 18 years of age) with a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of six months or longer in duration involving the trunk and/or limbs. Additional key inclusion criteria included a treatment area involving between two percent and 30 percent of the BSA, a physician global assessment (PGA) score of mild or moderate disease severity, and a modified psoriasis area and severity index (mPASI) score two or more. Eligible participants were randomized to treatment (3:1:3) with CAL/BDP cream, vehicle, or CAL/BDP TS. Identical packaging and labeling was used to ensure investigators were blinded to treatment allocation. Participants were instructed to apply the treatment topically once daily (preferable in the evening) to affected areas for eight weeks. The primary efficacy endpoint was the proportion of participants with treatment success at Week 8. Treatment success was defined as a minimum two-point decrease from baseline in PGA score to “clear” or “almost clear” disease. The PGA assessment was scored on a five-point scale representing the average lesion severity on the trunk and limbs (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). Secondary efficacy endpoints included the change in mPASI at eight weeks, assessment of treatment convenience after eight weeks on the psoriasis treatment convenience scale (PTCS), change in itch intensity (11-point numerical rating scale [NRS]) at Week 4, and the proportion of participants with four-point improvement in itch intensity on the NRS at Week 4. Safety assessments included the percentage and type of TEAEs.

Results: A total of 796 participants were enrolled at 55 clinical sites across the United States. Overall, 725 of 796 participants (91.1%) completed the trial. The discontinuation rate was 8.3 percent in the CAL/BDP cream group, 6.4 percent in the CAL/BDP TS group, and 18.3 percent in the vehicle group. The intent-to-treat (ITT) and safety population consisted of 794 participants (2 participants were excluded due to failure to receive or use the study treatment). Participant demographics and baseline characteristics were comparable between treatment groups. Participants randomized to the CAL/BDP cream treatment group achieved PGA treatment success in 37.4 percent of participants at Week 8, a significantly greater proportion of participants than the CAL/BDP TS (22.8%; p<0.0001) and vehicle (3.7%, p<0.0001) treatment groups. At the primary endpoint of eight weeks, PGA treatment success of CAL/BDP cream was 14.6 percentage points (95% CI: 7.6%, 21.6%) greater than CAL/BDP TS. Participants in the CAL/BDP cream treatment group also demonstrated significantly greater PGA treatment success at Week 4 compared to CAL/BDP TS (24.2% vs. 12.9%; p<0.0001). The incidence of TEAEs was similar across all three treatment groups. The most common application site-related TEAE reported by one percent or more of participants treated with CAL/BDP cream was application site irritation (1% vs. 0%). The most common other TEAEs reported by one percent or more of participants treated with CAL/BDP cream and more frequently than vehicle were upper respiratory infection (7% vs. 5%) and headache (2% vs. 0%). No serious TEAEs were assessed to be related to the trial medication.

Conclusion:CAL/BDP cream is a novel topical treatment for psoriasis, which through PAD™ Technology offers a unique combination of high efficacy, favorable safety, and excellent treatment convenience. In this head-to-head Phase III trial, treatment with CAL/BDP cream was associated with a significantly greater percentage of participants achieving treatment success compared with CAL/BDP TS or vehicle. CAL/BDP cream has favorable safety, with the most common application site–related TEAE being one percent application site irritation. Given these results, CAL/BDP cream can be considered a first-line therapy for the topical treatment of psoriasis.

Disclosures: LSG is an investigator, advisor, and/or speaker for MC2 Therapeutics, Leo Pharma, Dermavant, Arcutis, Ortho Dermatologics, Sun Pharma, Amgen, AbbVie, UCB, and BMS. LJG is an investigator, speaker, and/or consultant for Amgen, Arcutis, AbbVie, Dermavant, Lilly, MC2 Therapeutics, Novartis, Ortho Dermatologics, Sun Pharma, and UCB. SD is an investigator and consultant for AbbVie, Allergan, Galderma, Ortho, BMS, BI, MC2 Therapeutics, Lilly, and Dermira. MP and JS are employees of MC2 Therapeutics.

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: Results from a Phase II, randomized, double-blind, placebo-controlled trial

Presenters: Mease PJ,¹ Deodhar A,² van der Heijde D,³ Behrens F,⁴ Kivitz AJ,⁵ Kim J,⁶ Singhal S,⁶ Nowak M,⁶ Banerjee S⁶

Affiliations: ¹Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA; ²Oregon Health & Science University, Portland, OR; ³Leiden University Medical Center, Leiden, The Netherlands; ⁴CIRI/Rheumatology and Fraunhofer Institute IME, Translational Medicine and Pharmacology, Goethe University, Frankfurt, Germany; ⁵Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, PA; ⁶Bristol Myers Squibb, Princeton, NJ

Background: Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling by key cytokines involved in psoriatic arthritis (PsA) pathophysiology. Deucravacitinib is a novel oral agent that selectively inhibits TYK2 through an allosteric mechanism by binding to the regulatory domain of TYK2, in contrast to inhibitors of the closely related Janus kinases (JAK 1–3) that bind to the active site in the kinase domain.

Objective: This trial evaluated the efficacy and safety of deucravacitinib in PsA.

Methods: This is an ongoing, one-year, randomized, double-blind, PBO-controlled (initial 16 weeks), multicenter, Phase II trial (NCT03881059). Eligible patients had a PsA diagnosis for six months or longer, met CASPAR criteria, and had active disease (? 3 tender and ?3 swollen joints), C reactive protein 3mg/L or greater (ULN, 5 mg/L), and one or more psoriatic lesion (?2 cm). Patients had failed or were intolerant (IR) to one or more nonsteroidal anti-inflammatory drug, corticosteroid, and/or conventional synthetic disease-modifying antirheumatic drug (csDMARD), or one TNF inhibitor (TNFi;? 30%). Patients were randomized 1:1:1 to deucravacitinib 6mg once daily (QD) or 12mg QD, or PBO. The primary endpoint was ACR 20 response at Week 16. Key secondary endpoints included improvement from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI) and Short Form-36 Physical Component Score (SF-36 PCS). Additional endpoints included the proportion of patients achieving ACR 50/70, HAQ-DI response (? 0.35 improvement from baseline), minimal disease activity, enthesitis resolution (Leeds Index), and AEs.

Results: Of the 203 patients randomized, 180 (89%) completed 16 weeks of treatment. Demographic and baseline disease characteristics were similar across the three groups. Mean age was 49.8 years, median PsA duration was 4.5 years, 66 percent of patients were using csDMARDs at baseline, and 15 percent were TNFi-IR. The study met its primary objective of showing a dose-response relationship (P<0.001), with both deucravacitinib 6mg (n=70) and 12mg QD (n=67) demonstrating significantly greater ACR 20 responses versus PBO (n=66) at Week 16 (52.9% and 62.7% vs. 31.8%, respectively). Key secondary objectives were achieved with significant and generally similar improvements in secondary endpoints for both deucravacitinib doses versus PBO. The most common AEs in the deucravacitinib 6mg/12mg/PBO groups were nasopharyngitis (5.7%/17.9%/7.6%), sinusitis (0/7.5%/0), headache (7.1%/1.5%/4.5%), and rash (4.3%/6.0%/0). No serious AEs were reported in deucravacitinib-treated patients, including no serious infections, herpes zoster, opportunistic infections, or thrombotic events.

Conclusion: Deucravacitinib was efficacious versus PBO over 16 weeks of treatment in patients with active PsA. Treatment was well tolerated and the safety profile was consistent with that observed in an earlier Phase II psoriasis trial.

Efficacy and safety of long-term risankizumab treatment for nail, scalp, and palmoplantar psoriasis: An interim analysis from the open-label extension LIMMitless trial

Presenters: Elewski B,¹ Rich P,² Crowley J,³ Foley P,⁴ Zhan T,⁵ Zhao Y,⁵ Rubant S,⁵ Poulin Y⁶

Affiliations: ¹UAB School of Medicine, Dermatology, Birmingham, AL; ²Oregon Dermatology and Research Center, Portland, OR; ³Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield, CA; ⁴The University of Melbourne, St. Vincent’s Hospital Melbourne, and Probity Medical Research, Skin Health Institute, Melbourne, Australia; ⁵AbbVie Inc., North Chicago, IL; ⁶Laval University, Quebec City, Quebec, Canada

Background: Nail, scalp, and palmoplantar psoriasis can cause pain, impair function, restrict activities of daily living, and worsen quality of life, and can be difficult to treat. Risankizumab (RZB) is a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits IL-23 by targeting the p19 subunit, thus inhibiting psoriatic inflammation. We evaluated long-term efficacy and safety of RZB in treating nail, scalp, and palmoplantar psoriasis.

Methods: Long-term, continuous, RZB 150mg treatment for adults (? 18 years old) with moderate-to-severe plaque psoriasis was evaluated using integrated data from two double-blind, Phase III, base trials (UltIMMa-1 and -2, NCT02684370 and NCT02684357) and from an ongoing, Phase III, multicenter, international, open-label extension (OLE) trial (LIMMitless NCT03047395). Patients in the base trials who were randomized to RZB 150mg (dosed at Week 0, 4, and then every 12 weeks) and who completed the base trials, were candidates for long-term RZB treatment in the OLE, where they continued to receive open-label RZB 150mg every 12 weeks. Efficacy and safety were evaluated using an interim data cut at 172 weeks of continuous RZB treatment. Efficacy was assessed as the least squares mean percent improvement from baseline in Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Severity Index (PPASI), and Dermatology Life Quality Index (DLQI), and as achievement of DLQI 0/1 (no/little effect on psoriasis quality of life). All outcomes were calculated using an as-observed analysis for patients having outcome measurements for the reported endpoint. For each measurement at each visit, patients with non-missing measurement at the specific visit and non-zero measurement at baseline were included in the analysis. Safety of continuous RZB treatment was assessed by reported AEs.

Results: A total of 525 patients received continuous 150mg RZB every 12 weeks in the base studies and into the OLE, and 355 have completed 172 weeks of RZB treatment. Patients experienced improvement from baseline in each outcome at each timepoint the rate of achieving DLQI 0/1 increased to Week 124 and remained stable to Week 172 . As the study is ongoing, not all patients have reached each timepoint yet. Rates of AEs of interest (and events per 100 patient years) for the 525 patients in the safety analysis included: any AE 87.8 percent (157.8); serious AEs 13.5 percent (6.8), serious infections 3.0 percent (1.2), major adverse cardiac event 0.2 percent (<0.1), malignant tumors including/excluding nonmelanoma skin cancer 2.3 percent/1.1 percent (0.9/0.3), AEs leading to discontinuation of RZB 4.4 percent (1.4), deaths 0.6 percent (0.2) (n=3; 1 due to natural causes, 2 cause unknown, none related to RZB).

Conclusion: RZB provided durable maintenance of efficacy for nail, scalp, and palmoplantar Ps after long-term (172 weeks) every 12-week dosing. Safety was consistent with the known RZB safety profile; no new safety signals were observed.

Efficacy and safety of mirikizumab versus secukinumab and placebo in the treatment of moderate-to-severe psoriasis: 52-week results from OASIS-2, a multicenter, randomized, double-blind study

Presenters: Papp K,¹ Warren RB,² Green LJ,³ Reich K,⁴ Langley R,⁵ Paul C,⁶ Asahina A,⁷ Johnson L,⁸ Arora V,⁸ Osuntokun O,⁸ Lebwohl M⁹

Affiliations: ¹Probity Medical Research, Inc., Waterloo, Ontario, Canada; ²The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, United Kingdom;³George Washington University School of Medicine, Washington; ⁴Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and Skinflammation® Center, Hamburg, Germany; ⁵Dalhousie University, Halifax, Nova Scotia, Canada; ⁶Paul Sabatier University and Larrey Hospital, Toulouse, France; ⁷Jikei University School of Medicine, Tokyo, Japan; ⁸Eli Lilly and Company, Indianapolis, IN; ⁹Icahn School of Medicine at Mount Sinai, New York, NY

Background: Mirikizumab (miri) is a humanized, IgG4-variant monoclonal antibody that binds the p19-subunit of interleukin (IL)-23. We report efficacy and safety of miri from OASIS-2 (NCT03535194) for patients with moderate-to-severe psoriasis through Week 52 compared to placebo (PBO) and secukinumab (sec).

Methods: In this multicenter randomized, double-blind, placebo and active comparator-controlled study, 1465 patients were randomly assigned 4:4:4:1 to receive subcutaneously

Miri 250mg Q4W then 250mg Q8W starting at Week 16
Miri 250mg Q4W then 125mg Q8W starting at Week 16
Sec 300mg weekly for four weeks then Q4W starting at Week 4
Pbo Q4W then miri 250mg Q4W from Week 16 to 32 and Q8W thereafter.

Primary endpoints were proportion of patients achieving a static Physician’s Global Assessment (sPGA) of (0,1) with an improvement of at least two points from baseline and proportion of patients with at least a 90-percent improvement in Psoriasis Area and Severity Index (PASI90) at Week 16 compared to PBO. Major secondary endpoints included PASI75 and PASI100 compared to PBO at Week 16; sPGA (0,1) and PASI 90 noninferiority (NI) compared to sec at Week 16; and sPGA (0,1), PASI90, and PASI100 superiority compared to sec at Week 52. Cochran-Mantel-Haenszel test was used to compare treatment groups; missing data were imputed as nonresponse.

Results: Of 1465 patients, 91.1 percent completed 52 weeks of treatment. Primary objectives versus PBO and major secondary versus sec (NI) were met at Week 16. PASI 90 response rates for patients receiving PBO (n=112), sec (n=448), and miri 250mg (n=905) were 6.3 percent, 72.8 percent, and 74.4 percent, respectively; and sPGA (0,1) response rates were 6.3 percent, 76.3 percent, and 79.7 percent (p<0.001 for comparisons vs. PBO, and p<0.001 for NI comparisons vs. sec). At Week 16, 37.7 percent patients on miri achieved PASI100 (vs. 1.8% PBO). PASI90, sPGA (0,1), PASI100 at Week 52 (major secondary objectives) for both miri doses 125mg (81.4%/ 83.1%/ 53.9%, respectively) and 250mg (82.4%/ 83.3%/ 58.8%, respectively) were superior to sec (69.4%/ 68.5%/ 42.9%, respectively, all p-values <0.001).

During the combined induction and maintenance periods for the all miri safety population, most common TEAEs (? 5%) were nasopharyngitis (24.0%), upper respiratory tract infections (9.8%), headache (7.3%), back pain (5.9%), and arthralgia (5.3%). Serious AEs (3.9%) and discontinuations due to AEs (1.7%) were low and similar across active treatment arms. Four (0.4%) patients receiving miri during induction had major adverse cardiovascular events (MACE); three patients had risk factors. One event led to death from acute myocardial infarction in a patient with multiple risk factors and was judged unrelated to study drug. No patients on PBO during induction had an serious adverse event or ajor adverse cardiovascular event (MACE).

Conclusion: Miri demonstrated superiority compared to PBO on all primary and major secondary endpoints, noninferiority compared to sec on all major secondary endpoints at Week 16, and superiority for all major secondary endpoints compared to sec at Week 52. Safety was consistent with previous findings and other IL-23s. More MACE and cerebrocardiovascular events were observed in miri during induction period.

Halobetasol propionate lotion 0.05% in patients 12 to 16 years, 11 months of age with plaque psoriasis: Results from an open-label study evaluating adrenal suppression potential

Presenters: Laquer V,¹ Davidson D,² Nguyen A,¹ Nguyen T¹

Affiliations: ¹First OC Dermatology, Fountain Valley, CA; ²Medical Affairs Dermatology, Sun Pharmaceutical Industries, Inc., Princeton, NJ

Background: Halobetasol propionate (HBP) lotion 0.05% is a high-potency corticosteroid approved for topical treatment of plaque psoriasis in adults. Topical corticosteroids, and especially high-potency corticosteroids, have the potential of reversible hypothalamic-pituitary-adrenal (HPA) axis suppression. Measuring plasma or serum cortisol levels after stimulating the adrenal cortex with cosyntropin tests the HPA axis, reacting as a negative feedback mechanism. Effects of HBP on the HPA axis in children have not been previously evaluated.

Objective: We sought to examine the effects of HBP on HPA suppression in patients younger than 17 years of age with plaque psoriasis.

Methods: This was a Phase IV, open-label, multicenter study enrolling patients aged 12 to 16 years, 11 months in age with stable plaque psoriasis covering at least 10 percent of their BSA (excluding face, scalp, groin, axillae, and other intertriginous areas). A baseline cosyntropin stimulation test (CST) was performed at screening to determine HPA axis response; only patients with normal adrenal function were eligible to participate. Additional inclusion criteria included an Investigator Global Assessment (IGA) score of three or more at baseline. Patients applied a maximum of 50g weekly of 0.05% HBP lotion to all identified plaque psoriasis sites twice daily (approximately 12 hours apart) for up to two weeks or until the psoriasis cleared Assessments Safety. A CST was performed at baseline between 7 and 9AM for each patient. At the end of the study, a CST was performed within one hour of the time of the baseline CST and eight hours or more after applying a dose of 0.05% HBP. Abnormal HPA axis response was defined as poststimulation serum cortisol level 18?g/dl or less; if the patient had an abnormal response, they returned at least every four weeks for follow-up until HPA axis response returned to normal pharmacokinetic (PK) assessment was performed at screening, Day 8, and Day 15. At Day 15, the PK sample was obtained approximately 12 hours after application of the Day 14 evening dose of 0.05% HBP and immediately prior to the CST. AEs were reported during the study and coded using the Medical Dictionary for Regulatory Activities v20.0 The IGA assessed the overall severity of the patient’s plaque psoriasis based on scaling, erythema, and plaque elevation at screening, baseline, Day 8, and Day 15/end of study. The three areas were scored from 0 to 4, with 0 indicating clear and 4 indicating severe. Each assessment was a stand-alone assessment and the investigator was instructed not to refer to previous assessments. The percent BSA affected with plaque psoriasis was estimated at baseline, Day 8, and Day 15. Additionally, the percent BSA treated with 0.05% HBP was also estimated at baseline and Day 8.

Results: Overall, 19 patients were screened with 16 patients enrolling in the study; all patients who enrolled completed the study. The safety population (n = 16) included all patients who received ? one dose of 0.05% HBP. The evaluable population (n = 14) included all patients in the safety population and met the following criteria:

Screening CST with 30-minute poststimulation cortisol level >18?g/dl
Both screening and end of study CST conducted between 7 and 9 AM and the end of study CST conducted within one hour of the screening CST
Applied ?80 percent but ?120 percent of expected applications with final dose applied no more than 14 hours before the start of the CST
Did not take any medications that may interfere with HPA axis function
No other significant protocol deviations

Two patients did not meet the criteria for the evaluable population (end of study CST completed 6 days after last dose); these patients were also excluded from the PK population (n=14). The majority (62.5%) of patients were male and all were white and of Hispanic or Latino ethnicity. One patient—included in all three populations—had an abnormal HPA axis response at Day 15 (16.2?g/dl). The post-CST cortisol levels returned to normal at the approximate six-month follow-up visit. Throughout the study, plasma trough concentration of HBP was below quantifiable limit (0.02ng/mL) for 15 patients; One (6.3%) patient had a slightly elevated HBP trough concentration of 0.0282ng/mL. One (6.3%) patient experienced a mild TEAE of abnormal ACTH stimulation test; the AE resolved and the patient did not discontinue the study.At Day 15, two (14.3%) patients had IGA Grade 2, while the remaining patients had Grade 1 or Grade 0. At Day 15, the mean (range) percent BSA affected decreased to 2.8 percent (0%–10%). The mean (SD) change from baseline for percent BSA affected at Day 15 was ?8.7 (3.2) Similarly, at Day 15, the mean (range) percent BSA treated with 0.05% BHP decreased to 7.1 percent (3%–10%). The mean (SD) change from baseline for percent BSA treated with 0.05% HBP at Day 8 was ?4.1 (2.0)

Conclusion: HBP 0.05% was well tolerated by the pediatric patients and showed a similar safety risk as other corticosteroids in patients younger than 17 years of age. Most patients improved their IGA score by one point or more and had a decrease in both percent BSA affected with plaque psoriasis and percent BSA treated with 0.05% HBP. Overall, this study supports the use of 0.05% HBP lotion in children 12 years to 16 years, 11 months with minimal adrenal suppressive effects.

Funding: The study was funded by Sun Pharmaceutical Industries, Inc, (Princeton, NJ). Medical writing and support provided by Zehra Gundogan, VMD, of AlphaBioCom, LLC (King of Prussia, PA) and funded by Sun Pharmaceutical Industries, Inc.

Disclosures: VL has served on advisory boards for Almirall, Celgene, Leo Pharmaceuticals, Novartis, and Pfizer. DD is an employee of Sun Pharmaceutical Industries, Inc. AN has served on advisory boards and as a consultant for Celgene; Foamix; IntraDerm Pharmaceuticals; Leo Pharmaceuticals; Mayne; Novartis; Pfizer; Regeneron Sanofi; and Sun Pharmaceutical Industries, Inc.; and as a speaker for Amgen; Celgene; Eli Lilly; Encore Pharmaceuticals; Janssen; Leo Pharmaceuticals; Mayne; Novartis; Sun Pharmaceutical Industries, Inc.; and UCB. TN has served as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB; as an investigator for AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Sanofi Regeneron; and as a speaker for AbbVie; Almirall; Amgen; Celgene; Eli Lilly; Novartis; Pfizer; Sanofi Regeneron; and Sun Pharmaceutical Industries, Inc.

Patient perceptions of psoriatic disease in the United States: Results from the US subgroup of the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey

Presenters: Lebwohl M,¹ Ogdie A,² Merola JF,³ Gottlieb A,¹ Tang L,⁴ Richter S,⁴ Stein Gold L⁵

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Hospital of the University of Pennsylvania, Philadelphia, PA; ³Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; ⁴Amgen Inc., Thousand Oaks, CA; ⁵Henry Ford Health System, West Bloomfield, MI

Background: Patients with mild-to-moderate PsO report substantial disease burden despite having limited skin involvement. The UPLIFT survey was conducted among patients and physicians to better understand patient perspectives on treatment-related outcomes, particularly for patients with mild-to-moderate PsO and/or PsA.

Objective: We present patient-reported data from the US subgroup in UPLIFT.

Methods: UPLIFT was a multinational online survey conducted from March 2 to June 3, 2020. The patient survey included adults with self-reported PsO and/or PsA. Demographics, PsO in special areas (scalp, face, nails, palms/soles, or genitals), PsO-involved body surface area (BSA), patient-rated PsO severity (1 [very mild] to 10 [very severe]), DLQI, and current treatment were assessed in the US subgroup.

Results: Of the 3,806 patients with PsO and/or PsA completing the survey, 1,006 were in the US. In the US, 53 percent were diagnosed with PsO only, 40 percent had both PsO and PsA, and 7 percent had PsA only. Mean age was 46.3 years old, all patients reported comorbidities, and PsO in special areas was common. Among patients with limited skin involvement (BSA ? 3 palms; n=559), 56 percent rated their current PsO as moderate or severe and 74 percent had PsO in at least one special area. Among patients with BSA three or less and PsO in at least one special area (n=415), 59 percent of patients had a DLQI score over five (at least a moderate effect) and mean DLQI score was 10.5.

Conclusion: In the US subgroup of UPLIFT, more than half of patients with limited skin involvement reported their current disease as moderate or severe. Many had PsO in special areas and reported substantial disease burden, suggesting a persistent unmet need in this patient population.

Funding: This survey was funded by Amgen Inc. Writing support was funded by Amgen and provided by Amy Shaberman, PhD, of Peloton Advantage, LLC, an OPEN Health company.

Disclosures: ML is employed by Mount Sinai, AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research & Development, LLC, LEO Pharma, Ortho Dermatologics, Pfizer, and UCB, Inc. Research funds came from Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD Skincare, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica – consultant. AO is with Novartis and Pfizer with grant/research support from AbbVie, BMS, Lilly, Pfizer, Novartis, Takeda – consultant. JM is with AbbVie, Arena, Avotres, Biogen, Bristol-Myers Squibb, Celgene Corporation, Dermavant, Eli Lilly and Company, EMD Serono, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB – consultant and/or investigator. AG is with Abbott Labs (AbbVie), Actelion, Amgen, Inc., Akros, Astellas, Baxalta, Beiersdorf, Inc., Bristol-Myers Squibb Co., Can-Fite, Catabasis, Celgene Corporation, Centocor (Janssen), Inc., Coronado, CSL Behring Biotherapies for Life, Dermipsor Ltd., Genentech, GlaxoSmithKline, Incyte, Karyopharm, Kineta One, Lilly, Meiji Seika Pharma Co., Ltd, Mitsubishi Tanabe Pharma Development America, Inc., Novartis, Novo Nordisk, Pfizer, Takeda, Teva, UCB, Vertex, and XenoPort – consulting/advisory boards. LSG is with AbbVie, Amgen, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member LT and SR are with Amgen Inc.

Proactive management with twice-weekly topical Cal/BD foam prolongs treatment efficacy versus reactive management in patients with plaque psoriasis

Presenters: Stein Gold L,¹ Alonso-Llamazares J,² Laws P,³ Perrussel M,⁴ Yamauchi P,⁵ Thoning H,⁶ Toxvaerd C,⁶ Sticherling M⁷

Affiliations: ¹Henry Ford Medical Center, Detroit, Michigan; ²VA Medical Center, Miami, FL; ³Chapel Allerton Hospital, Leeds, United Kingdom; ⁴Centre Hospitalier Universitaire Pontchaillou, Université De Rennes, Rennes, France; ⁵Dermatology Institute and Skin Care Center, Santa Monica, CA; ⁶LEO Pharma A/S, Ballerup, Denmark; ⁷Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany

Background: In the recent PSO-LONG study (NCT02899962), long-term proactive management with calcipotriene 50µg/g / betamethasone dipropionate 0.5mg/g (Cal/BD) foam demonstrated superior efficacy versus reactive management in patients with plaque psoriasis, without new safety concerns.

Objective: We performed a PSO-LONG subanalysis of physician’s global assessment (PGA) of disease severity and modified psoriasis area and severity index (mPASI) scores to evaluate proactive versus reactive management for up to 52 weeks.

Methods: Following the initial FOUR-week, open-label lead-in phase (Cal/BD foam once daily), patients participating in the PSO-LONG study entered a 52-week randomized, double-blind maintenance phase and an eight-week follow-up period. At maintenance phase entry, patients were randomized to receive either proactive (continued Cal/BD foam) or reactive (vehicle foam) treatment twice weekly. Rescue treatment of Cal/BD once daily for four weeks was given to patients experiencing a relapse (PGA ? 2), in either treatment group. If PGA was less than two after four weeks, maintenance therapy resumed; otherwise, the patient was withdrawn if the PGA was 2 or more. mPASI and PGA scores were evaluated up to 52 weeks.

Results: In the open-label lead-in phase, 80 percent of patients (n=521) achieved treatment success with statistically significant changes from baseline to Week 4 in mPASI and PGA scores (mean difference [SD] 6.5 [3.5] and 2.2 [0.4], respectively; both P<0.0001). After four weeks of the maintenance phase, a clear separation in mean PGA scores for proactive versus reactive management was observed, which was maintained throughout the remainder of the study. Area under the curve (AUC) distribution for mean PGA score was 15 percent lower for the proactive versus the reactive group throughout the maintenance phase (1.35 vs. 1.59; difference ?0.23, P=0.0001). Similarly, the AUC distribution for mean mPASI score was 20 percent lower for the proactive versus reactive group throughout the maintenance phase (2.27 vs. 2.84; difference ?0.57, P=0.0005). The proportion of symptom-free days (defined as PGA 0/1) was significantly greater in the proactive versus reactive group (mean 256 vs. 218 days; P<0.001). Symptom-free days as assessed by mPASI-90, mPASI-75, and mPASI ? three were significantly greater in the proactive vs reactive group (mean 106 vs. 72; 206 vs. 169; 288 vs. 259 days, respectively, all P<0.001).

Conclusion: These findings show that long-term proactive management of adult patients with plaque psoriasis using twice-weekly topical Cal/BD foam for up to 52 weeks was associated with sustained and significantly lower mean mPASI/PGA scores, and a significantly greater number of days in remission, compared with reactive management.

Funding: The PSO-LONG study was sponsored by LEO Pharma A/S, Ballerup, Denmark.

Rates of treated depression and anxiety among patients with psoriasis or psoriatic arthritis treated with apremilast, biologics, conventional DMARDs, and corticosteroids in a US commercial database

Presenters: Vasilakis-Scaramozza C,¹ Persson R,¹ Hagberg KW,¹ Khilfeh I,² Paris M,² Jick S^1,3

Affiliations: ¹Boston Collaborative Drug Surveillance Program, Lexington, MA; ²Amgen Inc., Thousand Oaks, CA; ³Boston University School of Public Health, Boston, MA

Background: Depression and anxiety are common among patients with psoriasis and PsA, but rates may differ by treatment.

Objective: Our study compares rates of treated depression and/or anxiety by psoriasis/PsA treatment type in a population of patients with psoriasis or PsA.

Methods: We conducted a population-based cohort study of treated psoriasis/PsA patients using the MarketScan database (2014–2018). Cohort entry was the date of first claim for a study drug (apremilast, tumor necrosis factor inhibitor [TNF-i], IL-17, IL-23 or IL-12/23 inhibitor [IL-i], conventional DMARDs (cDMARDs; methotrexate, cyclosporine), or systemic corticosteroids) after March 21, 2014 (apremilast’s US approval). All patients required continual enrollment for at least one year before cohort entry. Patients with antidepressant/anti-anxiety treatment before cohort entry were considered prevalent cases and excluded. We also excluded patients with a history of cancer or other autoimmune diseases before cohort entry. A patient was considered currently exposed to a drug from each claim date through the prescription days supply +30 days (+60 days for injections, +120 days for IL-12/23). Cases of incident treated depression, anxiety, or anxiety+depression were defined as patients with a claim for an antidepressant/antianxiety medication within 30 days of a diagnosis of anxiety or depression or both, and at least seven days after cohort entry. Patients were followed from cohort entry through censor date: index date (date patient became a case), end of enrollment, or end of study (October 31, 2018). We calculated incidence rates (IRs), adjusted incidence rate ratios (IRR; reference: apremilast) and 95% confidence intervals (CIs) for each outcome per 1,000 patient-years. IRR were adjusted for sex, indication, age, calendar year, and history of psychiatric disorders.

Results: The study population included 67,189 patients (median age at cohort entry: 50 years, 44% female, 23% PsA±psoriasis, 77% psoriasis only; 12% history of untreated depression/anxiety, other psychiatric diagnoses or antipsychotic treatments). Among the 1,125 treated depression cases, IRs were lowest among apremilast monotherapy users and higher for biologics, corticosteroids, and non-apremilast combination users. IRs (95% CIs) were as follows: apremilast monotherapy, 5.6 (3.7–8.1); apremilast+other, 6.6 (2.8–13.0); cDMARDs only, 7.8 (6.2–9.8); biologics only, 9.3 (8.4–10.3); biologics with cDMARDs and/or corticosteroids, 9.8 (7.6–12.4); corticosteroids only, 10.9 (9.2–12.9); and cDMARDs+corticosteroids, 13.9 (8.8–20.8). Adjusted IRRs (95% CIs) of treated depression, with apremilast as reference, were as follows: cDMARDs only, 1.4 (0.9–2.2); biologics only, 1.8 (1.1–2.7); biologics with cDMARDs and/or corticosteroids, 1.7 (1.1–2.7); corticosteroids only, 1.8 (1.2–2.8); cDMARDs+corticosteroids, 2.4 (1.4–4.2); and crude IRR apremilast+other, 1.2 (0.5–2.6).

Among 1,347 treated anxiety cases and 708 treated anxiety+depression cases, IRs were similar between treatments and IRRs did not differ from apremilast, with the exception of an elevated rate of anxiety+depression in users of apremilast+other (adjusted IRR 2.7 [1.5-5.0]).

Conclusion: In this real-world analysis, apremilast monotherapy was not associated with an increased risk of treated anxiety and/or depression. Treated depression rates among apremilast users were low compared with other psoriasis/PsA treatments. Rates of treated anxiety and treated anxiety+depression were similar across all psoriasis/PsA treatments, except for an elevated rate of anxiety+depression in users of apremilast+other.

Funding: Funding was provided by Amgen Inc.

Selective inhibition of tyrosine kinase 2 (TK2) with deucravacitinib compared with Janus kinase (JAK) 1–3 Inhibitors

Presenters: Chimalakonda A, Burke J, Cheng L, Catlett I, Patel A, Shen J, Girgis IG, Banerjee S, Throup J

Background: Deucravacitinib is a novel, oral, allosteric agent that selectively inhibits intracellular signaling by binding to the TYK2 pseudokinase domain rather than to the conserved active site in the kinase domain. The high functional selectivity for TYK2 versus other signaling tyrosine kinases has been confirmed in cellular assays (Burke JR et al. Sci Transl Med. 2019;11:1–16). Kinase selectivity should provide a differentiated risk/benefit profile due to potent TYK2 inhibition and minimal activity against other kinases. In a 12-week, Phase II trial in moderate to severe plaque psoriasis, deucravacitinib had a favorable safety profile, and 67 to 75 percent of patients achieved Psoriasis Area and Severity Index (PASI) 75 after 12 weeks at doses ? 3mg twice daily versus 7 percent with placebo (P<0.001; Papp K et al. N Engl J Med. 2018;379:1313–1321).

Objective: The objective of this analysis was to understand the selectivity profile of deucravacitinib for TYK2 versus the related JAKs 1?3, compared with the approved JAK inhibitors tofacitinib (Tofa), upadacitinib (Upa), and baricitinib (Bari), at clinically relevant doses and plasma concentrations.

Methods: In vitro whole-blood assays were developed to measure the activity of common intracellular pairings of signaling tyrosine kinases (JAK 1/3, JAK 2/2, and TYK2/JAK2). Deucravacitinib, Tofa, Upa, and Bari concentrations providing half-maximal inhibition (IC50) of relevant signaling readouts were determined. Whole-blood IC50 values were plotted against known pharmacokinetic profiles of these agents at doses evaluated in Phase III trials, including approved doses. Time durations that concentrations were greater than IC50 and projected average daily inhibition were evaluated.

Results: At clinically relevant doses and exposures, deucravacitinib plasma concentrations were higher than the TYK2 whole-blood IC50 for a considerable part (8–16 hours) of the day. The maximal plasma concentration (C_max) of deucravacitinib was > 9- to 18-fold lower than the JAK 1/3 whole-blood IC50 and >52- to >109-fold lower than the JAK 2/2 whole-blood IC50, indicating lack of meaningful inhibition of JAK 1–3 by deucravacitinib at clinically relevant doses. Average daily inhibition of TYK2 by deucravacitinib ranged from 54 to 70 percent. Tofa, Upa, and Bari exhibited varying degrees of daily average inhibition against JAK 1/3 (70%–94%) and JAK 2/2 (23%–67%). Projected Cmax values of Tofa, Upa, and Bari were 17- to 33-fold lower than TYK2 IC50, indicating minimal or no meaningful inhibition of TYK2.

Conclusion: Deucravacitinib has high functional selectivity for TYK2 at clinically relevant doses and plasma concentrations. In contrast, Tofa, Upa, and Bari variably inhibit JAK 1–3 but not TYK2 at clinically relevant concentrations. These results indicate that deucravacitinib is a distinct class of signaling kinase inhibitor compared with JAK 1–3 inhibitors. Ongoing studies in multiple immune-mediated inflammatory diseases including plaque psoriasis, psoriatic arthritis, lupus, and inflammatory bowel disease will further assess the safety and efficacy of deucravacitinib.

Funding: This analysis was sponsored by Bristol Myers Squibb. Professional medical writing from Ann Marie Fitzmaurice, PhD and editorial assistance were provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and were funded by Bristol Myers Squibb.

Disclosures: AC, LC, IC, AP, JS, IGG, SB, and JT are employees and shareholders of Bristol Myers Squibb. JB was an employee and shareholder of Bristol Myers Squibb at the time this analysis was conducted.

Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Efficacy and safety in two pivotal Phase III trials

Presenters: Lebwohl M,¹ Stein Gold L,² Strober B,³ Papp K,⁴ Armstrong A,⁵ Bagel J,⁶ Kircik L,^1,7 Ehst H,⁸ Hong H,⁹ Soung J,¹⁰ Fromowitz J,¹¹ Guenthner S,¹² Piscitelli SC,¹³ Rubenstein DS,¹³ Brown PM,¹³ Tallman AM,¹³ Bissonnette R¹⁴

Affiliations: ¹Icahn School of Medicine, Mount Sinai, New York, NY; ²Henry Ford Health System, Detroit, MI;³Yale University, New Haven and Central Connecticut Dermatology Research, Cromwell, CT;⁴Probity Medical Research, Waterloo, Ontario, Canada; ⁵Keck School of Medicine University of Southern California, Los Angeles, CA;⁶Psoriasis Treatment Center of New Jersey, NJ;⁷Skin Sciences, PLLC, Louisville, KY; ⁸Oregon Medical Research Center, Portland, OR; ⁹University of British Columbia and Probity Medical Research, Surrey, British Columbia, Canada; ¹⁰Southern California Dermatology, Santa Ana, CA; ¹¹Dermatology of Boca, Boca Raton, FL; ¹²The Indiana Clinical Trials Center, PC, Plainfield, IN; ¹³Dermavant Sciences, Inc., Durham, NC; ¹⁴Innovaderm Research Inc., Montreal, Quebec, Canada

Background: There is a need for efficacious topical therapies for plaque psoriasis without concerns for duration of treatment due to potential for long-term adverse effects or local intolerance. However, no topicals with novel mechanisms have been introduced in recent years. Tapinarof is a novel therapeutic aryl hydrocarbon receptor modulating agent (TAMA) in development for the treatment of psoriasis and atopic dermatitis.

Objective: We report pivotal Phase III efficacy and safety results for tapinarof cream 1% once daily (QD) in the treatment of adult patients with mild to severe plaque psoriasis.

Methods: Two identical, randomized, double-blind, vehicle-controlled trials assessed efficacy and safety of tapinarof cream 1% QD in patients with mild to severe plaque psoriasis. Adults aged 18 to 75 years old with a baseline Physician Global Assessment (PGA) score of 2–4 and BSA involvement of ? 3– ? 20 percent were randomized 2:1 to tapinarof cream 1% or vehicle QD for 12 weeks. The primary efficacy endpoint was PGA response, defined as the proportion of patients with a PGA score of clear (0) or almost clear (1) and at least a 2-grade improvement from baseline at Week 12. A key secondary efficacy endpoint was PASI75 from baseline at Week 12. Efficacy endpoints were derived from the intent-to-treat population using multiple imputation analysis.

Results: In total, 510 and 515 patients were randomized in PSOARING 1 and PSOARING 2; overall, at baseline, 79.2 percent and 83.9 percent of patients had a PGA score of 3; mean PASI score was 8.9 and 9.1; and mean BSA affected was 7.9 percent and 7.6 percent, respectively in each study. At Week 12, both the primary PGA and secondary PASI75 efficacy endpoints were met with high statistical significance, in the tapinarof 1% QD groups versus vehicle, respectively: PGA response rates were 35.4 percent versus 6.0 percent and 40.2 percent versus 6.3 percent (both P<0.0001); and PASI75 rates were 36.1 percent versus 10.2 percent and 47.6 percent versus 6.9 percent (both P<0.0001). Most adverse events (AEs) were mild or moderate, consistent with previous studies, and did not lead to study discontinuation. Most common AEs (? 5% in any group) were folliculitis, nasopharyngitis, and contact dermatitis.

Conclusion: Tapinarof cream 1% QD demonstrated highly statistically significant and clinically meaningful efficacy compared with vehicle for both primary and secondary efficacy endpoints and was well-tolerated over 12 weeks in patients with plaque psoriasis. Tapinarof cream has the potential to provide physicians and patients with a novel non-steroidal topical treatment option that is effective and well tolerated.

Funding: These studies were funded by Dermavant Sciences, Inc.

ROSACEA

Integrated safety and efficacy analysis of FMX103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea: Results from two Phase III studies

Presenters: Del Rosso JQ,¹ Stein Gold L,² Kircik L,³ Bhatia ND,⁴ Sadick N,⁵ Zirwas M,⁶ Lain E,⁷ Stuart I⁸

Affiliations: ¹JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; ²Henry Ford Health System, Detroit, MI; ³Icahn School of Medicine, New York, NY; ⁴Therapeutics Clinical Research, San Diego, CA; ⁵Sadick Dermatology, New York, NY; ⁶Sanova Dermatology, Austin, TX; ⁷Dermatologists of the Central States, Columbus, OH; ⁸VYNE Therapeutics Inc, Bridgewater, NJ

Background: FMX103 1.5% minocycline foam is a novel topical medication being developed for the treatment of moderate-to-severe papulopustular rosacea.

Objective: Integrated safety and efficacy analysis of two Phase III, randomized, multicenter, double-blind, vehicle-controlled studies (FX2016-11, N=751, and FX2016-12, N=771) comparing FMX103 1.5% versus vehicle foam in the treatment of moderate-to-severe papulopustular rosacea.

Methods: Subjects applied the assigned drug once daily for 12 weeks. Coprimary efficacy endpoints were the absolute change from baseline to Week 12 in inflammatory lesions and the proportion of subjects achieving IGA treatment success at Week 12. Safety endpoints included adverse events (AEs), physical exams, vital signs, laboratory tests, and local facial tolerability assessments.

Results: The integrated efficacy population consisted of 1,522 subjects (FMX103 1.5%, n=1009; vehicle, n=513), predominantly female (70.6%), and ranging in age from 18 to 86 years old. Overall for the pooled population, FMX103 1.5% demonstrated statistically significant advantages over vehicle foam for both the change from baseline to Week 12 in inflammatory lesions (P<0.001) and the proportion of subjects achieving IGA treatment success at Week 12 (P<0.001). This statistical advantage of FMX103 1.5% over vehicle foam was observed for both co-primary endpoints in sub-populations of subjects that had either moderate (IGA-3) or severe (IGA=4) baseline disease severity. Notably, the reduction from baseline to Week 12 in inflammatory lesions was more pronounced in the severe subpopulation. Treatment-emergent AEs (TEAEs) were experienced by 22.4 percent of subjects, with the incidence balanced between treatment groups (FMX103, 21.7%; vehicle, 23.8%). The most frequently reported TEAEs, in the FMX103 1.5% and vehicle groups, respectively, were viral upper respiratory tract infection (2.4% vs. 2.3%) and upper respiratory tract infection (1.9% vs. 2.5%). Similar rates of mild, moderate, and severe TEAEs were observed across both treatment groups. Serious TEAEs occurred in eight subjects (0.3% for FMX103 1.5%; 1.0% for vehicle); all were unrelated to treatment. TEAEs leading to drug withdrawal occurred in nine subjects (0.7% for FMX103 1.5%; 0.4% for vehicle); only one was considered related (moderate pruritus, FMX103 1.5%). For the facial tolerability assessments at Week 12, both groups had higher percentages of subjects reporting “none” versus baseline, and the assessments trended toward improving scores.

Conclusion: This pooled analysis demonstrated that FMX103 1.5% appears to be a safe and efficacious topical treatment option for the treatment of moderate-to-severe facial papulopustular rosacea.

WOUND HEALING

The treatment of wounds associated with recessive dystrophic epidermolysis bullosa with local injections of gene-corrected, collagen VII-expressing autologous human dermal fibroblasts

Presenters: Marinkovich MP,^{1, 2} Sridhar K,¹ Kakarla V,¹Yonchek M,³ Blumenthal R,³ Spellman M³

Affiliations: ¹Stanford University School of Medicine, Stanford, CA; ²Veterans Affairs Medical Center, Palo Alto, CA; ³Castle Creek Biosciences, Exton, PA

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder caused by mutations in the COL7A1 gene encoding type VII collagen (COL7).

Objective: This study examined the feasibility of correcting these mutations by providing a wild type COL7A1 gene. Local injection of COL7-expressing autologous human dermal fibroblasts (D-Fi, also known as FCX-007) led to wound healing in patients with RDEB.

Methods: Six subjects (9–38 years of age) with various COL7A1 mutations resulting in undetectable COL7 expression and a lack of intact anchoring fibrils enrolled in this Phase I/II clinical study. Subject fibroblasts, isolated from their respective skin biopsies, were transduced with a third-generation self-inactivating lentiviral vector encoding the wild type COL7A1 gene, and expanded. Eligible treatment wounds were chronically present prior to treatment and excluded those that had evidence of infection, were previously treated or located on mucous membranes, face, hands and feet. Intradermal injections with gene-corrected fibroblasts were completed on Day 1 and comparator wounds were not treated. Four of the six subjects received a second treatment four to 52 weeks after the initial injection; all were to be followed through 52 weeks.

Results: At 12 weeks, 80 percent (8/10) of treated wounds (4.3 cm² to 34.1 cm²) demonstrated complete wound healing, compared to zero percent of the untreated comparator wounds. Linear COL7 expression at the dermal-epidermal junction and restoration of AF was confirmed in treated sites. No treatment emergent serious adverse reactions were reported. No replication competent virus nor significant antibody responses to COL7 were detected through 52 weeks.

Conclusion: The local injection of gene-corrected autologous fibroblasts to the wounds of RDEB appears to be generally safe, and complete wound healing is typically exhibited. The durability of wound healing will be evaluated over a longer period in a Phase III clinical study.

Disclosures: This study was supported by Castle Creek Biosciences.