Selected Abstracts from Maui Derm 2023 for Dermatologists

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J Clin Aesthet Dermatol. 2023;16(4 Suppl 1):S5–S31.


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

Dear colleagues,

The 2023 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 2023 meeting. It is my hope that you will find the highlighted research informative and thought provoking. 

George Martin, MD

Maui Derm 2023 Program Director; Guest Editor, The Journal of Clinical and Aesthetic Dermatology

Funding for this supplement was provided by Amgen.

 

CONTENT

ACNE

  • Advancement of personalized photopneumatic therapy for rapid, visible improvement in patients with mild-to-moderate acne
  • Comparison of investigator global assessment (IGA) and patient’s global assessment (ptGA) of acne vulgaris among patients with moderate-to-severe non-nodular acne vulgaris (AV) administered sarecycline in community practices across the US: Analysis of PROSES study results
  • Efficacy and safety of a fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel for moderate-to-severe acne: Randomized Phase 2 and Phase 3 studies of the first triple-combination drug
  • Impact of acne on social functioning, emotional functioning, and activities of daily living (ADL) among patients with moderate-to-severe non-nodular acne vulgaris (AV) administered sarecycline in real-world community practices across the US (PROSES Study)
  • Phase 3 pooled analysis of safety and efficacy of trifarotene 0.005% cream within adolescent population
  • Tazarotene 0.045% lotion for truncal acne: efficacy, tolerability, and spreadability

ACTINIC KERATOSIS

  • Clinician assessment of overall appearance of the skin in the treated area, among patients with actinic keratosis treated with tirbanibulin in community practices across the US (PROAK study)
  • Patient’s global assessment of overall appearance of the skin in the treated area, among patients with actinic keratosis treated with tirbanibulin in community practices across the US (PROAK study)

ALOPECIA

  • Efficacy of baricitinib in patients with various degrees of alopecia areata severity: Results from BRAVE-AA1 and BRAVE-AA2
  • Efficacy of the oral JAK3/TEC inhibitor ritlecitinib (PF-06651600) in patients with alopecia areata over 48 weeks: results from the ALLEGRO Phase 2b/3 randomized, double-blind, placebo-controlled trial

ATOPIC DERMATITIS 

  • Dupilumab: a comparison of infection rates across atopic dermatitis trials in adults, adolescents, children, and infants
  • Eblasakimab improves multiple disease measures in adult patients with moderate-to-severe atopic dermatitis in a randomized, double-blinded, placebo-controlled, Phase 1 study
  • Efficacy of abrocitinib and dupilumab on chronic hand eczema in patients with moderate-to-severe atopic dermatitis: Results from the Phase 3 JADE DARE study
  • Efficacy of nemolizumab in atopic dermatitis: Rapid impact on EASI and SCORAD components
  • Greater skin clearance and itch improvement in atopic dermatitis are associated with the achievement of stringent patient-reported outcomes: Integrated analysis of three upadacitinib Phase 3 trials
  • High-level responses across multiple domains in patients with atopic dermatitis treated with abrocitinib versus dupilumab: A post-hoc analysis of a Phase 3 randomized trial
  • Incremental improvements after switching from dupilumab (DUPI) to upadacitinib (UPA) in the heads up open-label extension (OLE) study
  • Lebrikizumab treatment improves four EASI clinical signs over 16 weeks in moderate-to-severe atopic dermatitis
  • Real-world psychosocial and economic burden of atopic dermatitis related to disease severity and use of systemic therapy: Results from a multicountry study
  • Rocatinlimab demonstrates improvements in head and neck atopic dermatitis in patients with moderate-to-severe disease in a Phase 2 trial
  • Safety of tralokinumab in pediatric patients aged 12–17 with moderate-to-severe atopic dermatitis: results from the Phase 3 ECZTRA 6 trial
  • Tapinarof cream 1% once daily for the treatment of extensive atopic dermatitis in adolescents and children: 4-week maximal-use trial
  • Three years of tralokinumab treatment provides long-term disease control as demonstrated by clinically meaningful outcomes in moderate-to-severe atopic dermatitis

CUTANEOUS ONCOLOGY

  • Clinical performance of novel elastic scattering spectroscopy (ESS) in detection of skin cancer: a blinded, prospective, multi-center clinical trial
  • Clinical utility of an elastic scattering spectroscopy device in assisting primary care physician’s detection of skin cancers
  • Differentiating seborrheic keratoses with a blue-white veil from melanomas
  • Hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200mg daily: Results from the 42-month BOLT study
  • Improving patient selection for adjuvant therapy: Considerations for the role of the 31-gene expression profile
  • Incorporating the 40 gene expression profile (40-GEP) test for poorly differentiated cutaneous squamous cell carcinoma (cSCC) tumors mitigates risk assessment uncertainty from histologic grading
  • The efficacy and safety of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light for the treatment of facial cutaneous squamous cell carcinoma in situ

HIDRADENITIS SUPPURATIVA

  • Secukinumab in moderate-to-severe hidradenitis suppurativa: Primary endpoint analysis from the SUNSHINE and SUNRISE Phase 3 trials

MISCELLANEOUS

  • Dupilumab efficacy in patients with chronic spontaneous urticaria by IgE level: LIBERTY-CSU CUPID Study A
  • Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: Pooled results from two Phase 3 trials (LIBERTY-PN PRIME and PRIME2)
  • Efgartigimod: clinical development of a novel neonatal Fc receptor antagonist in the treatment of autoimmune diseases
  • Evaluation of a novel inorganic tinted sunscreen enriched with five antioxidants for protection against UVA1 and VL induced hyperpigmentation and erythema
  • Evaluation of an SPF50 sunscreen containing photolyase and antioxidants for its anti- photoaging properties
  • Long-term safety and tolerability of remibrutinib (LOU064) in Phase 2b study in chronic spontaneous urticaria patients
  • Onychomycosis dermatophytoma treatment: A systematic review of the literature

PSORIASIS

  • Bimekizumab efficacy through one year in patients with moderate-to-severe plaque psoriasis in subgroups defined by prior biologic treatment: Pooled results from four Phase 3/3b trials
  • Bimekizumab maintenance of response through three years in patients with moderate-to-severe plaque psoriasis who responded at Week 16: Results from the BE BRIGHT open-label extension trial
  • Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: Analysis of pooled data from up to three years of treatment in Phase 2 and 3 clinical trials
  • Bimekizumab speed of response in patients with moderate-to-severe plaque psoriasis: Results from four Phase 3/3b trials (BE VIVID, BE READY, BE SURE, and BE RADIANT)
  • Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the Phase 3 POETYK PSO program
  • Durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-Week, Phase 2 open-label safety trial
  • Efficacy and safety of apremilast in patients with genital psoriasis: Results from the Phase 3, randomized, placebo-Controlled, double-blind DISCREET study
  • Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a Phase 2, randomized, double-blind, placebo-controlled study
  • Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the KEEPsAKE 1 and KEEPsAKE 2 trials
  • Efficacy and safety results of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-Week results from SPROUT, a Phase 3, randomized, controlled study
  • Exposure–Response analysis demonstrates response to tapinarof is driven by local Effects at sites of application
  • Patients’ quality of life in a Phase 4 real-world study of tildrakizumab in moderate-to-severe plaque psoriasis
  • Tapinarof cream 1% once daily for plaque psoriasis: improvements in quality of life and clinical efficacy in two pivotal Phase 3 trials
  • Tapinarof inhibits the formation, cytokine production, and persistence of resident memory T cells in vitro

ROSACEA

  • A study of encapsulated benzoyl peroxide cream, 5%: effects on the microbiome and biophysical properties of the skin in subjects with moderate-to-severe rosacea

 


ACNE


Advancement of personalized photopneumatic therapy for rapid, visible improvement in patients with mild-to-moderate acne

Presenters: Munavalli GS,1 Smith JL,2 Smith TR3

Affiliations: 1Dermatology, Laser & Vein Specialists of the Carolinas; 2 Northwest Georgia Dermatology & Skin Surgery Center.

Background: Photopneumatic therapy (PPT) combines vacuum and pulsed, targeted wavelength broadband light. Vacuum suction gently extracts debris and bacteria from the ostia of the pilosebaceous units; specific light wavelengths destroy proinflammatory bacterial porphyrins produced by Cutibacterium acnes and may reduce sebum production.

Objective: To evaluate, via photographs, changes in visible acne lesions and skin texture after a series of tailored PPT treatments delivered to patients with mild-moderate acne.

Methods: Patients of all skin types aged 14 to 55 years with inflammatory, comedonal and pustular lesions on the face were eligible to receive 4 to 5 in office photopneumatic treatments (TheraClear X, Strata Skin Sciences) 1 to 2 weeks apart for 15 min/treatment. All patients were photographed (baseline). Vacuum settings were tailored for treatment areas; all received a double pulse of 500-1200nm (wavelength based on severity) with one to two passes over affected area(s). Photographs were taken prior to each session. Visible lesions and local skin reactions were evaluated.

Results: All patients (n=10) experienced a visible reduction in comedones, pustules and inflammatory facial acne lesions. Redness reduction and improvement in skin texture, pore size, and perilesional erythema were observed in treatment area(s). Most responded with 2 to 3 treatments; a female patient with persistent perioral acne experienced complete clearance. Adverse effects were infrequent and limited to mild erythema, mild bruising, superficial erosions, and temporary changes in pigmentation.

Conclusion: PPT was well tolerated with visible improvement in acne lesions and skin texture regardless of skin type. PPT used as part of a mild-to-moderate acne treatment regimen may optimize lesion clearance without medication and/or as an adjuvant. Tailored vacuum suction strength and light wavelength based on an individual patient’s acne severity allows delivery of precision therapy consistent with the recent personalized acne care pathway expert recommendations.

 

Comparison of investigator global assessment (IGA) and patient’s global assessment (ptGA) of acne vulgaris among patients with moderate-to-severe non-nodular acne vulgaris (AV) administered sarecycline in community practices across the US: Analysis of PROSES study results

Presenters: Stein Gold L,1 Alexis AF,2 Harper JC,3 Graber E,4 Baldwin H,5 Kircik L,6 Del Rosso,7 Fried RG,8 Rieder EA,9 Hebert A,10 Narayanan S,11 Koscielny V,12 Kasujee I12

Affiliations: 1Henry Ford Health System, Bloomfield, MI; 2Weill Cornell Medical College, New York, NY; 3The Dermatology and Skin Care Center of Birmingham, Birmingham, AL; 4The Dermatology Institute of Boston and Northeastern University, Boston, MA; 5Acne Treatment and Research Center, Brooklyn, NY; 6Icahn School of Medicine, Mount Sinai, New York, NY; 7JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 8Yardley Dermatology Associates, Yardley, PA; 9New York University Grossman School of Medicine, New York, NY; 10UTHealth McGovern Medical School, Houston, TX; 11Avant Health LLC, Bethesda, MD; 12Almirall SA, Barcelona, Spain.

Background: The objective of this analysis was to compare facial IGA and patient’s Global assessment (ptGA) of AV at baseline and Weeks 4, 8 and 12, among AV patients administered sarecycline in community practices across the US

Methods: A single-arm, prospective cohort study (PROSES) was conducted with moderate-to-severe non-nodular AV patients older than 9 years who were prescribed sarecycline in real-world community practices in the US Facial IGA of patient’s AV status was reported by the study clinician and ptGA of AV was collected as part of validated ASIS questionnaire; both measures used a five-point adjectival response scale of 0 (clear), 1 (almost-clear), 2 (mild), 3 (moderate), 4 (severe), and collected at baseline and Weeks 4, 8 and 12. Proportion of patients with clear/almost clear AV per IGA and ptGA were analyzed for all study timepoints.

Results: A total of 253 AV patients completed the study (adults 60.08%; pediatric 39.92%; female: 66.40%; Caucasian/white: 68.38%, African-American: 8.70%; Other-races: 22.92%; moderate AV: 86.56%; severe AV: 13.44%). At baseline, 0 percent and 4.74 percent were clear/almost clear, per IGA and ptGA respectively. At Week-4, 9.09 percent and 29.18 percent were clear/almost-clear, per IGA and ptGA respectively. At Week-8, 33.99 percent and 41.84 percent were clear/almost-clear, per IGA and ptGA respectively. At Week-12, 58.89 percent and 59.29 percent were clear/almost-clear, per IGA and ptGA respectively. Increase in proportion of patients with clear/almost clear over time, as measured by IGA and ptGA were respectively statistically significant at p<0.0001.

Conclusion: Within the study cohort administered sarecycline, a narrow-spectrum, tetracycline-derived antibiotic, for 12 weeks, proportion of patients with clear/almost clear facial AV (as measured by clinicians and patients respectively) increased significantly, with almost six out of 10 patients achieving clear/almost clear facial AV at Week 12.

 

Efficacy and safety of a fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel for moderate-to-severe acne: Randomized Phase 2 and Phase 3 studies of the first triple-combination drug

Presenters: Stein Gold L,1 Kircik LH,2-4 Tanghetti5 Baldwin H6,7 Draelos Z8; Gold M,9 Lain E,10 Pariser DM,11,12 Sadick N,13,14 Pillai R,15 Bhatt V15

Affiliations: 1Henry Ford Hospital, Detroit, MI; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Indiana University Medical Center, Indianapolis, IN; 4Physicians Skin Care, PLLC, DermResearch, PLLC, and Skin Sciences, PLLC, Louisville, KY; 5Center for Dermatology and Laser Surgery, Sacramento, CA; 6The Acne Treatment and Research Center, Brooklyn, NY; 7Robert Wood Johnson University Hospital, New Brunswick, NJ; 8Dermatology Consulting Services, PLLC, High Point, NC; 9Tennessee Clinical Research Center, Nashville, TN; 10Austin Institute for Clinical Research, Austin, TX; 11Eastern Virginia Medical School, Norfolk, VA; 12Virginia Clinical Research, Inc., Norfolk, VA; 13Department of Dermatology, Weill Cornell Medical College, New York, NY; 14Sadick Dermatology, New York, NY; 15Bausch Health US, LLC*, Petaluma, CA

Background: A three-pronged approach to acne treatment—combining an antibiotic, antibacterial, and retinoid—may provide greater efficacy and tolerability than single/double treatments while potentially reducing antibiotic resistance and increasing patient compliance. Clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% (IDP-126) gel is the first triple-combination, fixed-dose topical acne product in development that addresses the major pathophysiological abnormalities in acne patients. The efficacy, safety, and tolerability of IDP-126 gel was evaluated in Phase 2 and 3 studies of patients with moderate-to-severe acne.

Methods: A Phase 2 (N=741; NCT03170388) and two Phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, randomized, 12-week studies enrolled participants aged ≥9 years with moderate-to-severe acne. Participants were randomized to receive once-daily IDP-126 or vehicle; the Phase 2 study included three additional randomization arms containing dyad gels: BPO/adapalene; clindamycin phosphate/BPO; and clindamycin phosphate/adapalene (data not shown). Endpoints included participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in inflammatory and noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were also assessed.

Results: In all three studies at Week 12, half of participants achieved treatment success with IDP-126 (Phase 2: 52.5%; Phase 3: 49.6%, 50.5%) versus less than one-fourth with vehicle (8.1%; 24.9%, 20.5%; P<0.01, all). IDP-126 resulted in over 70% reductions in inflammatory and noninflammatory lesions at Week 12, significantly greater than vehicle (range: inflammatory, 75.7%-80.1% vs 50.4%-59.6%; noninflammatory, 71.0%-73.3% vs 45.8%-49.0%; P<0.001, all). Most TEAEs were of mild-moderate severity, and less than 4 percent of IDP-126-treated participants discontinued study/treatment due to AEs.

Conclusion: The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in three clinical studies of children, adolescents, and adults with moderate-to-severe acne.

Funding: Funding was provided by Ortho Dermatologics.

 

Impact of acne on social functioning, emotional functioning, and activities of daily living (ADL) among patients with moderate-to-severe non-nodular acne vulgaris (AV) administered sarecycline in real-world community practices across the US (PROSES Study)

Presenters: Fried RG,1 Rieder EA,2 Alexis AF,3 Baldwin H,4 Graber E,5 Harper JC,6 Stein Gold L,7 Hebert A,8 Del Rosso J,9 Kircik L,10 Grada A,11 Narayanan S,12 Koscielny V,13 Kasujee I13

Affiliations: 1Yardley Dermatology Associates, Morrisville, PA; 2New York University Grossman School of Medicine, New York, NY; 3Weill Cornell Medical College, New York, NY; 4Acne Treatment and Research Center, Brooklyn, NY; 5The Dermatology Institute of Boston and Northeastern University, Boston, MA; 6The Dermatology and Skin Care Center of Birmingham, Birmingham, AL; 7Henry Ford Health System, Bloomfield, MI; 8UTHealth McGovern Medical School, Houston, TX; 9JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 10Icahn School of Medicine, Mount Sinai, New York, NY; 11Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH; 12Avant Health LLC, Bethesda, MD; 13Almirall SA, Barcelona, Spain.

Background: Understanding of AV impact on patient Health-related quality of life (HRQoL) is still evolving.

Objective: The key objective of this analysis was to evaluate patientperceived impact of AV on emotional/social functioning and ADL through a novel Expert Panel Questionnaire (EPQ), among AV patients administered sarecycline, an oral narrow-spectrum, tetracycline-derived antibiotic, in real-world community practices across the US

Methods: A single-arm, prospective cohort study (PROSES) was conducted with moderate-to-severe non-nodular AV patients aged 9 years or older who were prescribed sarecycline. Primary endpoint included 11-item EPQ responses (completed by patients (>12years) and caregivers (for patients 9-11 yrs) at Week 12 and corresponding change from baseline (CFB)). All items were scored on a five-point adjectival response scale (score=0/1 (never/rarely, not at all/slightly/a little), score=2 (some of the time, somewhat), and score=3/4 (most of the time/all of the time, moderately/extremely, quite a bit/very much). The EPQs related to AV impact on emotional functioning (EPQ 1-4), social functioning (EPQ 5-7), and ADL (EPQ 8-11) were formulated based on dermatology expert panel consensus using modified Delphi method. CFB in proportion of patients reporting score=0/1 (no/least impact) for EPQ items at Week-12 were analyzed.

Results: A total of 253 AV patients completed the study (adults: 60.08%; pediatric: 39.92%; female: 66.40%). CFB in patients reporting score=0/1 (no/least impact) for each EPQ item increased statistically significantly (p<0.0001) except for EPQ10. In emotional functioning domain, CFB=31.62 percent for EPQ1 on patients’ mood/anger; CFB= 28.85 percent, 20.95 percent, 38.74 percent respectively for EPQ2, EPQ3, EPQ4 on hopelessness/worries about skin. In social functioning domain, CFB=23.72 percent for EPQ5 on patients’ social media/selfie activity, CFB=22.93 percent for EPQ6 on impact on real-life plans, and CFB=21.34 percent for EPQ7 on efforts to hide AV. In ADL domain, CFB=15.02 percent for EPQ8 on picked-on/judged due to AV, CFB=13.83 percent for EPQ9 on ability to reach future goals, and CFB=0.99 percent for EPQ10 on parent understanding of AV concerns (for patients<18yrs), and CFB=18.18 percent for EPQ11 on sleep impact.

Conclusion: Patients reporting no/least AV burden in emotional functioning, social functioning, and ADL significantly increased in patients with moderate-to-severe AV who were administered sarecycline for 12 weeks.

 

Phase 3 pooled analysis of safety and efficacy of trifarotene 0.005% cream within adolescent population

Presenters: Hebert A,1 Lee S,2 Krowchuk D,3 Arekapudi KL,4 Kwong P5

Affiliations: 1UTHealth McGovern School of Medicine and Children’s Memorial Hermann Hospital, University of Texas, Houston, TX; 2Rady Children’s Hospital and University of California San Diego, San Diego, CA; 3Wake Forest School of Medicine, Winston-Salem, NC; 4Galderma Laboratories, LLC, Fort Worth, TX; 5Private Practice, Jacksonville, FL

Background: Acne vulgaris is common among adolescents.1 Clinicians need to have an action plan for assessing and managing acne in daily practice.

Methods: Post-hoc analysis of two Phase 3 pivotal trials of trifarotene 0.005% cream in patients with moderate facial and truncal acne. The studies were of identical double-blind, randomized, vehicle-controlled design. Analysis included efficacy, safety, and tolerability variables in the subgroup of subjects aged 12 to 17 years, inclusive.

Results: There were 1,128 adolescent subjects (n=571 received trifarotene, n=557 vehicle). Facial investigator global assessment (IGA) success (score 0/1) at Week 12 was 30.4 percent with trifarotene versus 17.6 percent with vehicle (P<0.001). Reductions in facial lesion counts were significantly greater with trifarotene vs vehicle (inflammatory lesions, 56.8% vs 43.2%; non-inflammatory lesions 50.1% vs 36.0%, P<0.001 for both). Truncal acne success rates were 35.1 percent for trifarotene versus 23.5 percent for vehicle (P<.001). Mean reduction of truncal lesions were 58.5 percent in inflammatory and 26.5 percent in noninflammatory lesions with trifarotene; in the vehicle group, reductions were 45.5 percent in inflammatory lesions and 37.9 percent in non-inflammatory lesions (P<0.001 for both comparisons). There was a low and acceptable rate of adverse events and tolerability was favorable. Adverse events occurred in 28.3 percent of trifarotene-treated subjects vs 23.5 percent of vehicle-treated subjects; adverse events rarely led to study discontinuation (1.9% trifarotene, 0.2% vehicle). Skin irritation, typical of topical retinoid therapy, occurred and was consistent with the adult population. The majority of adverse events mild-to-moderate, typically occurred within the first four weeks of treatment, and decreased with continued use of trifarotene.

Conclusion: Trifarotene monotherapy was associated with good clinical efficacy, safety, and tolerability in adolescent subjects aged 12 to 17 years with moderate acne. Once-daily application offers convenience for patients, and the low concentration of trifarotene makes it well-suited to use on large body surface areas such as trunk.

Funding: This study was funded by Galderma Research & Development, LLC.

 

Tazarotene 0.045% lotion for truncal acne: efficacy, tolerability, and spreadability

Presenters: Kircik LH1-3 Draelos ZD,4 Guenin E5

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY; 2Indiana University Medical Center, Indianapolis, IN; 3Physicians Skin Care, PLLC, DermResearch, PLLC, and Skin Sciences, PLLC, Louisville, KY; 4Dermatology Consulting Services, PLLC, High Point, NC; 5Ortho Dermatologics*, Bridgewater, NJ. 

Background: Topical treatment of truncal acne (on the chest and/or back) is complicated by the involvement of a large body surface area, necessitating formulations that are highly spreadable and non-irritating. Tazarotene 0.045% lotion was developed using polymeric emulsion technology to provide uniform and rapid distribution of tazarotene and moisturizing/hydrating excipients in a highly spreadable formulation. 

Objective: Here, we summarize the efficacy, safety, and tolerability of tazarotene in the treatment of truncal acne as well as its irritation potential and spreadability.

Methods: Three studies evaluated tazarotene 0.045% lotion on the trunk. Study 1 was a 12-week, Phase 4, open-label study, where subjects (≥12 years; N=19) with moderate truncal acne (Investigator’s Global Assessment [IGA] score=3) were treated with once-daily tazarotene lotion. Outcomes included IGA score, lesion counts, cutaneous tolerability, and adverse events (AEs). Study 2 was a modified cumulative irritation patch test used to assess irritation in healthy adults (N=20), with repeated placement of patches loaded with tazarotene 0.045% lotion, trifarotene 0.005% cream, or control (no drug) on the upper back over 12 days. Study 3 was a double-blind, split-body study of healthy adults (N=30). Spreadability was compared for tazarotene lotion and trifarotene cream applied to subjects’ backs.

Results: After 12 weeks of treatment with tazarotene lotion in Study 1, 89 percent of subjects (17/19) achieved clear/almost clear truncal skin (IGA score of 0 or 1; P<0.001 vs baseline). Large reductions from baseline in inflammatory, noninflammatory, and total lesion counts were also observed (83%, 64%, and 82%, respectively; P<0.01, all). Significant improvements from baseline in IGA score and lesion counts were observed as early as Week 4. There were no AEs related to tazarotene treatment. At baseline and Week 12, most subjects (≥74%) had no tolerability issues, and there were no significant changes from baseline to Week 12 in any tolerability assessment (erythema, dryness, peeling, oiliness, pruritus, and burning). In the patch test study, tazarotene was associated with minimal irritation over 12 days of exposure; tazarotene lotion was significantly less irritating than trifarotene cream two days after the first patch application and continuing through Day 12. In the split-body spreadability study, tazarotene lotion covered on average approximately 30 percent more skin than the same amount of trifarotene cream.

Conclusion: Tazarotene 0.045% lotion significantly reduced truncal acne lesions and was well tolerated after 12 weeks of once-daily use. This easy-to-apply lotion was associated with less irritation and had greater skin coverage compared with trifarotene 0.005% cream. Overall, tazarotene 0.045% lotion is an effective and well tolerated option for the treatment of truncal acne, with sensory and aesthetic properties preferred by patients.

Funding: Funding for this study was provided by Ortho Dermatologics.

 


ACTINIC KERATOSIS


Clinician assessment of overall appearance of the skin in the treated area, among patients with actinic keratosis treated with tirbanibulin in community practices across the US (PROAK study)

Presenters: Berman B,1 Armstrong A,2 Bhatia N,3 Del Rosso JD,4 Kircik L,5 Lebwohl M,5 Patel VA,6 Rigel D,5 Schlesinger T,7 Narayanan S,8 Koscielny V,9 Kasujee I9

Affiliations: 1University of Miami Miller School of Medicine, Miami, FL, USA; 2Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Therapeutics Clinical Research, San Diego, CA, USA; 4JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, USA; 5Mount Sinai Icahn School of Medicine, New York, NY, USA; 6George Washington School of Medicine and Health Sciences, Washington, DC, USA; 7Clinical Research Center of the Carolinas, Charleston, SC, USA; 8Avant Health LLC, Bethesda, MD, USA; 9Almirall SA, Barcelona, Spain

Background: The objective of this analysis was to evaluate clinician’s assessment of overall appearance of the skin in the treated area, among patients with AKs treated with tirbanibulin in community practices across the US

Methods: A single-arm, prospective cohort study (PROAK: NCT05260073) was conducted among adult patients with AKs on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the US, as part of usual care. Patients and clinicians completed surveys and clinical assessments at baseline, Week 8 (timeframe for main endpoints) and Week 24. Clinicians rated the overall appearance of patient’s skin in the tirbanibulin-treated area at Week 8 on a five-point adjectival response scale of 0 (much worse), 1 (somewhat worse), 2 (no change), 3 (somewhat improved), 4 (much improved).

Results: A total of 290 patients with AKs completed the study assessments at Week 8 (female: 31.38%; history of skin cancer: 61.72%; Fitzpatrick Skin Type: I: 7.59%, II: 71.38%, III: 18.62%, IV: 1.38%, V: 1.03%). Patient self-reported skin-texture was – dry: 39.66 percent, smooth: 47.59 percent, rough: 19.66 percent, bumpy: 18.62 percent, scaly: 35.17 percent, blistering/peeling: 6.55 percent. All patients (100%) completed their 5-day once-daily treatment course. At Week 8, clinicians reported that the overall appearance of the skin ‘somewhat/much improved’ in the tirbanibulin-treated area for 91.03 percent of patients; for 6.90 percent of patients, clinicians reported ‘no change’; for 2.07 percent of patients, clinicians reported ‘somewhat/much worse’.

Conclusion: For a majority of patients, clinicians reported improvement in the overall appearance of the skin at Week 8 in the tirbanibulin-treated area, among patients with AKs administered once-daily tirbanibulin treatment for 5-days as part of usual care.

 

Patient’s global assessment of overall appearance of the skin in the treated area, among patients with actinic keratosis treated with tirbanibulin in community practices across the US (PROAK study)

Presenters: Armstrong A,1 Berman B,2 Bhatia N, 3 Del Rosso J,4 Kircik L,5 Lebwohl M,5 Patel VA,6 Rigel D,5 Schlesinger T,7 Narayanan S,8 Koscielny V,9 Kasujee I9

Affiliations: 1Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2University of Miami Miller School of Medicine, Miami, FL, USA; 3Therapeutics Clinical Research, San Diego, CA, USA; 4JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, USA; 5Mount Sinai Icahn School of Medicine, New York, NY, USA 6George Washington School of Medicine and Health Sciences, Washington, DC, USA; 7Clinical Research Center of the Carolinas, Charleston, SC, USA; 8Avant Health LLC, Bethesda, MD, USA; 9Almirall SA, Barcelona, Spain

Objective: The objective of this analysis was to evaluate patient’s global assessment of overall appearance of the skin in the treated area, among patients with AKs treated with tirbanibulin in community practices across the US

Methods: A single-arm, prospective cohort study (PROAK: NCT05260073) was conducted among adult patients with AKs on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the US, as part of usual care. Patients and clinicians completed surveys and clinical assessments at baseline, Week 8 (timeframe for main endpoints) and Week 24. Self-reported changes to overall appearance of the skin in the tirbanibulin-treated area was collected from patients at Week 8 on a five-point adjectival response scale of 0 (much worse), 1 (somewhat worse), 2 (no change), 3 (somewhat improved), 4 (much improved).

Results: A total of 290 patients with AKs completed the study assessments at Week 8 (female: 31.38%; history of skin cancer: 61.72%; Fitzpatrick skin type: I: 7.59%, II: 71.38%, III: 18.62%, IV: 1.38%, V: 1.03%). Patient self-reported skin-texture was – dry: 39.66 percent, smooth: 47.59 percent, rough: 19.66 percent, bumpy: 18.62 percent, scaly: 35.17 percent, blistering/peeling: 6.55 percent. All patients (100%) completed their 5-day once-daily treatment course. At Week-8, 84.14 percent of the patients reported that their overall appearance of the skin as ‘somewhat/much improved’ in the tirbanibulin-treated area, while 14.48 percent reported ‘no change’, and 1.38 percent reported ‘somewhat/much worse’.

Conclusion: A majority of patients with AKs administered once-daily tirbanibulin treatment for 5-days reported improvement in the overall appearance of the skin in the tirbanibulin-treated area, at Week 8.

 


ALOPECIA


Efficacy of baricitinib in patients with various degrees of alopecia areata severity: Results from BRAVE-AA1 and BRAVE-AA2

Presenters: Taylor SC,1 Korman NJ,2 Tsai TF,3 Feely M,4-5 Dutronc Y,4 Wu WS,4 Petto H,4 Tosti A6

Affiliations: 1Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 2University Hospitals Cleveland Medical Center, and the Murdough Family Center for Psoriasis, Cleveland, OH, USA; 3Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan; 4Eli Lilly and Company, Indianapolis, IN, USA; 5Mount Sinai School of Medicine, New York, NY, USA; 6Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA

Background: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor with demonstrated efficacy in patients with alopecia areata (AA). This analysis evaluated the difference in response among subgroups of patients with various degree of severity based on the Severity of Alopecia Tool (SALT) score from Phase 3 results of two randomized, double-blinded, placebo-controlled trials (BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259)).

Methods: Both BRAVE-AA1 (N=654) and BRAVE-AA2 (N=546) enrolled adult patients with ≥50% scalp hair loss. Severity of scalp hair loss at baseline was defined as severe AA (SALT score 50-94) or very severe AA (SALT score 95-100). In addition, investigators were asked to record patients considered as alopecia universalis (AU). The primary efficacy endpoint was the proportions of patients achieving SALT score ≤20 at Week 36. Data analyses are presented for each subgroup using Fishers exact test.

Results: Overall, 1200 adult patients were enrolled with 46.8 percent and 53.2 percent of patients qualifying as severe and very severe, with 44.3 percent identified as AU. At Week 36, both BARI 2mg and BARI 4mg were significantly superior to placebo for the proportion patients achieving SALT ≤20 across all subgroups: severe AA (BARI 2mg: 32.7% p<0.001; BARI 4 mg: 47.6% p<0.001 vs placebo: 7.8%), very severe AA (9.8% p<0.001; 21.3% p<0.001 vs 0.6%) and AU (19.6% p<0.001; 27.7% p<0.001 vs 2.9%).

Conclusion: BARI 2mg and BARI 4mg demonstrated superiority over placebo in achieving hair regrowth (SALT ≤20) at Week 36 in adult patients across the various degrees of severity of scalp hair loss.

Funding: This study was funded by Eli Lilly and Company, under license from Incyte Corporation.

Disclosures: SC Taylor has been an investigator for: Concert Pharmaceuticals, Croma-Pharma, Eli Lilly and Company, Immune Tolerance Network, and Pfizer; has been a consultant, speaker, and/or advisory board member for: AbbVie, Arcutis, Beiersdorf, Biorez, CannTec, Evolus, Galderma Laboratories, Glo Getter Aesthetics, Johnson & Johnson Consumer Products, L’Oreal USA, LuminDx, Medscape/WebMD, Scientis, and Vichy Laboratoires; and has received book royalties from: McGraw Hill; 

NJ Korman has received grants, research support, and/or honoraria from and/or has served as a speaker and/or consultant for: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, ChemoCentryx, Eli Lilly and Company, Galderma, Genentech, Immune Pharma, Janssen, Kyowa Kirin, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Principia Biopharma, Regeneron, Sun Pharma, Trevi Therapeutics, UCB Pharma, and Xbiotech; 

TF Tsai has been a consultant for and/or been on the speakers bureau for: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, GlaxoSmithKline Stiefel, Janssen Cilag, Novartis, Pfizer, and UCB Pharma; 

M Feely is a clinical instructor at: Mount Sinai Hospital; is a current employee and shareholder of: Eli Lilly and Company; and has received consulting fees from: Aerolase, Castle Biosciences, Galderma, Revian, Sonoma Pharmaceuticals, Sun Pharma, and Suneva Medical; 

Y Dutronc, WS Wu, and H Petto are employees and shareholders of: Eli Lilly and Company; A. Tosti has been a compensated consultant and/or advisory board member for: Eli Lilly and Company, sponsor of the study; has been a consultant for: Almirall, Bristol Myers Squibb, DS Laboratories, Monat Global, Myovant Sciences, Pfizer, Procter & Gamble, and Thirty Madison; and has been a Principal Investigator for: Concert Pharmaceuticals, Eli Lilly and Company, and Erchonia

 

Efficacy of the oral JAK3/TEC inhibitor ritlecitinib (PF-06651600) in patients with alopecia areata over 48 weeks: results from the ALLEGRO Phase 2b/3 randomized, double-blind, placebo-controlled trial

Presenters: Mesinkovska, N1 Shapiro J,2 King B,3 Sinclair R,4 Zhang X,5 Lynde C,6 Harcha WG,7 Szepietowski JC,8 Wajsbrot D,9 Takiya L,10 Wolk R11

Affiliations: 1School of Medicine, University of California, Irvine, CA, USA; 2New York University School of Medicine, New York, NY, USA; 3Yale University School of Medicine, New Haven, CT, USA; 4Sinclair Dermatology, Melbourne, Victoria, Australia; 5The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Chin; 6Department of Medicine, University of Toronto, Toronto, Canada; 7Skinmed, Santiago de Chile, Chile; 8Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland 9Pfizer, New York, NY, USA; 10Pfizer, Collegeville, PA, USA; 11Pfizer, Groton, CT, USA

Background: The ALLEGRO Phase 2b/3 trial (NCT03732807) investigated the efficacy and safety of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with alopecia areata (AA). This analysis evaluated the efficacy of ritlecitinib over a 48-week treatment period.

Methods: Patients 12 years or older with AA and 50 percent scalp hair loss or more received daily ritlecitinib ± a 4-week loading dose (200/50 mg, 200/30mg, 50mg, 30mg, 10mg [assessed for dose-ranging only]) or placebo for 24 weeks. During the subsequent 24-week extension period, ritlecitinib groups continued maintenance doses through Week 48; patients initially on placebo switched to ritlecitinib 200/50mg or 50mg. Endpoints included: proportions of patients with Severity of Alopecia Tool [SALT] score ≤20 (primary), ≥2-grade improvement in eyebrows/eyelashes, and Patients’ Global Impression of Change (PGI-C) score of “moderately improved” or “greatly improved”.

Results: Overall, 718 subjects were randomized. Significantly higher proportions of patients receiving ritlecitinib vs. placebo had SALT ≤20 response as early as Week 8 for the 200/50mg group (P=0.008), Week 12 for 200/30mg (P=0.010) and Week 18 for 50mg (P<0.001) and 30mg (P=0.008). Proportions of patients with SALT ≤20 response increased through Week 48: 40 percent (200/50mg), 34 percent (200/30mg), 43 percent (50mg), 31 percent (30 mg) and 10 percent (10mg). Proportions of patients with ≥2-grade improvement in eyebrows/eyelashes or PGI-C response also increased up to Week 48 across ritlecitinib groups. Events of herpes zoster (8), pulmonary embolism (1) and breast cancer (2) were reported. No major adverse cardiovascular events, deaths or opportunistic infections were reported.

Conclusion: Ritlecitinib demonstrated sustained efficacy over 48 weeks in patients with AA with ≥50% scalp hair loss.

Funding: This study was funded by Pfizer.

Disclosures: LT, DW, RF, AF, and RW are employees of Pfizer and hold stock or stock options in Pfizer. NM provided professional services for Abbvie, Arena Pharmaceuticals, Bristol-Meyers Squibb, Concert Pharmaceuticals Inc, Eli Lilly, La Roche Posay and Pfizer. 

BK has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for Abbvie, Aclaris Therapeutics Inc, AltruBio Inc, Almirall, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol-Meyers Squibb, Concert Pharmaceuticals Inc, Dermavant Sciences Inc, Eli Lilly and Company, Incyte Corp, LEO Pharma, Otsuka/Visterra Inc, Pfizer, Regeneron, Sanofi Genzyme, TWi Biotechnology Inc, and Viela Bio; he is on speaker bureaus for Pfizer, Regeneron and Sanofi Genzyme. 

WG has served as a scientific advisor and/or clinical study investigator for Pfizer, Galderma, GSK, Eucerin, Johnson & Johnson, Janssen, Sanofi, BioNOOX, Beiersdorf/Eucerin. 

JCS has served as a scientific advisor/consultant for AbbVie, Leo Pharma, Novartis, Sandoz, Sanofi-Genzyme, Trevi, Viofor; speaker for AbbVie, Janssen-Cilag, Eli-Lilly, Lep Pharma, Sanofi-Genzyme; investigator for AbbVie, Amgen, BMS, Galderma, Galapagos, Incyte, InfraRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, Trevi. 

JS declares has served as consultant and/or clinical study investigator for Pfizer, Lilly, Regenlab, Eirion, 30 Madison; and is a stockholder of 30 Madison. 

CL has served as a speaker and/or consultant for AbbVie, Altius, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Dermavant, Eli Lilly, Fresnius Kabi, GSK, Innovaderm, Intega Skin, Janssen, Kyowa, La Roche Posay, LEO Pharma, L’Oreal, Medexus, Merck, P&G, Pediapharm, Regeneron, Roche, Sanofi Genzyme, Sentrex, TEVA, Tribute, UCB, Valeant, and Viatris, and as a principal investigator for AbbVie, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Dermavant, Eli Lilly, GSK, Innovaderm, Janssen, Kyowa, LEO Pharma, L’Oreal, Merck, Pediapharm, Regeneron, Roche, Sanofi Genzyme, Tribute, UCB, Valeant. 

RS declares providing professional services to Aerotech, Abbvie, AStra Zenica, Akesobio, Arena, Arcutis, Amgen, Ascend, Bayer, Boehringer Bristol Myer Squibb, Ingelheim, Celgene, Coherus Biosciences, Cutanea, Connect, Demira, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, LEO Pharma, MedImmune, Merck &Co, MSD, Novartis, Oncobiologics, Pfizer, Regeneron, Reistone, Roche, Samson Clinical, Sanofi, UCB and Sun Pharma. 

 


ATOPIC DERMATITIS


Dupilumab: a comparison of infection rates across atopic dermatitis trials in adults, adolescents, children, and infants

Presenters: Lio P,1 Beck LA,2 Shi VY,3 Chen Z,4 Khokhar FA,4 Cyr SL,4 Gonzalez T5

Affiliations: 1Northwestern University, Feinberg School of Medicine, IL; 2University of Rochester Medical Center, NY; 3University of Arkansas for Medical Sciences, AR; 4Regeneron Pharmaceuticals, Inc., NY; 5Sanofi, MA; USA.

Background: Moderate-to-severe atopic dermatitis (AD) is associated with increased frequency of infections which can lead to hospitalizations. Some treatments used for moderate-to-severe AD can be associated with increased risk of infection, contributing to a limitation of their long-term use. Dupilumab is a biologic agent targeting the shared signaling pathway for IL-4 and IL-13 and has not been associated with increased risk of overall skin infection rates in clinical trials.

Methods: We analyzed exposure-adjusted infection rates (number of patients per 100 patient-years, nP/100PY) during study treatment periods for MedDRA terms under the System Organ Class Infections and Infestations (overall infections), including adjudicated skin infections (excluding herpetic infections) and High Level Term Herpes Virus Infections. Patients with moderate-to-severe AD enrolled in Phase 2 (adults) or Phase 3 clinical studies received: young children (6months-5years, NCT03346434 part B): dupilumab 200/300mg (n=83) every four weeks (q4w) or placebo (n=78) with topical corticosteroids (TCS); children (6-11years, NCT03345914): dupilumab 300mg q4w (n=120), 100/200mg q2w (n=122), or placebo (n=120) with TCS; adolescents (12 -17years, NCT03054428): dupilumab 300 q4w (n=83), 200/300mg q2w (n=82), or placebo (n=85); adults (NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, NCT02755649): dupilumab 300mg q2w (n=746), 300mg qw (n=1095), or placebo (n=1091). Rates for dupilumab doses are provided in the order specified above. Post-hoc nominal P-values are between dupilumab and placebo.

Results: Rate of overall infections (nP/100PY) in dupilumab-treated groups was numerically lower than in the placebo group in young children (placebo: 246; dupilumab: 185) and children (placebo: 244; dupilumab: 184, 171) and similar between groups in adolescents (placebo: 204; dupilumab: 210, 181), and adults (placebo: 129; dupilumab: 134, 126). Adjudicated non-herpetic skin infection rates (nP/100PY) were significantly lower in most dupilumab-treated groups compared with placebo in young children (placebo: 93; dupilumab: 43 [P<0.05]), children (placebo: 48; dupilumab: 20 [P<0.05], 28 [n.s.]), and adults (placebo: 27; dupilumab: 16 [P<0.01], 14 [P<0.0001]) and numerically lower in adolescents (placebo: 70; dupilumab: 34, 34). Overall herpes infection rates (nP/100PY) in dupilumab-treated groups were similar to placebo in young children (placebo: 17; dupilumab: 20), children (placebo: 17; dupilumab: 5, 11), adolescents (placebo: 12; dupilumab: 16, 4), and adults (placebo: 10; dupilumab: 15, 11). Infection rates (nP/100PY) of clinically important herpetic infections, eczema herpeticum and herpes zoster, were numerically lower in dupilumab-treated young children (placebo: 4; dupilumab: 0), adolescents (placebo: 4; dupilumab: 0,0), and adults (placebo: 4; dupilumab: 2 [n.s.], 1 [P<0.01]), and numerically higher in children (placebo: 0; dupilumab: 3, 3).

Conclusion: Dupilumab treatment in children as young as 6 months of age, adolescents and adults with AD is generally associated with lower rates of non-herpetic skin infections compared with placebo and did not increase risk of overall infections in these data sets.

 

Eblasakimab improves multiple disease measures in adult patients with moderate-to-severe atopic dermatitis in a randomized, double-blinded, placebo-controlled, Phase 1 study

Presenters: Veverka KA,1 Menezes J,1 Thng S,2 Gooderham M,3 Simpson E4

Affiliations: 1ASLAN Pharmaceuticals, Menlo Park, CA, and Singapore; 2Skin Research Institute of Singapore, Agency for Science Technology & Research, Singapore; National Skin Center, Singapore; 3SKiN Centre for Dermatology, Peterborough, ON, Canada; Queens University, Kingston, ON, Canada; Probity Medical Research, Waterloo, ON, Canada; 4Department of Dermatology, Oregon Health & Science University, Portland, OR, USA

Background: Interleukin (IL)-4 and IL-13 are key drivers of atopic dermatitis (AD). Both signal through a shared type-2 receptor, a heterodimer comprised of IL-4Rα and IL-13Rα1. Eblasakimab, a first-in-class, fully human monoclonal antibody binds IL-13Rα1 with high affinity and blocks the signaling of IL-4 and IL-13 through the type-2 receptor. A randomized, double-blind, placebo-controlled, Phase 1b multiple ascending dose monotherapy study [NCT04090229] evaluated the safety, tolerability, and clinical properties for eblasakimab vs. placebo in adult patients with moderate-to-severe AD. Top line results have been reported previously (Blauvelt 2022, AAD). The objective of this study was to further analyze secondary endpoints of clinical relevance and post-hoc subgroup analyses.

Methods: Three cohorts were randomized to receive 200, 400 or 600mg eblasakimab or placebo subcutaneously weekly for eight weeks in a multiple ascending dose study design. Adult participants had chronic AD present for three or more years before screening, and the following parameters at screening and baseline: eczema area and severity index (EASI) ≥16, Investigator’s Global Assessment (IGA) score ≥3, ≥10% body surface area (BSA) of AD involvement. Rescue medication was not allowed. Efficacy assessments included percent change from baseline (%CFBL) in EASI, proportions of participants with 50 percent, 75 percent or 90 percent improvement in EASI score (EASI-50, EASI-75, EASI-90) or IGA 0/1, and %CFBL in percent BSA involvement. Inferential statistical analysis was performed for 600mg vs. placebo groups at Week 8 only.

Results: Improvements in EASI score were seen early and progressed over the trial duration with eblasakimab treatment vs. placebo. Significant improvements in %CFBL in EASI score at Week 8 were noted for eblasakimab 600mg vs. placebo (-65% vs. -27%, P=0.014). The difference in adjusted means was apparent by Week 6. Improvements were observed in the proportions of participants taking eblasakimab vs. placebo who achieved EASI-50 (81% vs. 31%), EASI-75 (69% vs. 15%) and EASI-90 (38% vs. 15%) at Week 8. At Week 8 a higher percentage of participants achieved an IGA 0/1 for eblasakimab 600mg vs. placebo (44% vs. 15%, P=0.107); mean %CFBL in BSA was -51% vs. -13%, respectively. Rates of moderate-to-severe AEs were comparable between 600mg and placebo. AEs related to treatment were similar between groups. AEs leading to treatment discontinuation were higher in the placebo group. One SAE was reported in the study considered unrelated to treatment. No deaths were reported.

Conclusion: Eblasakimab was well tolerated with significant improvements vs. placebo in several efficacy outcomes in a Phase 1b study in adults with moderate-to-severe AD.

 

Efficacy of abrocitinib and dupilumab on chronic hand eczema in patients with moderate-to-severe atopic dermatitis: Results from the Phase 3 JADE DARE study

Presenters: Bissonnette R,1 Worm M,2 Shi VY,3 Zhang F,4 Chan G,4 Bratt T,4 Kerkmann U,5 Clibborn C6

Affiliations: 1Innovaderm Research, Montreal, QC, Canada; 2Campus Charité Mitte, Universitätsmedizin Berlin, Berlin, Germany; 3University of Arkansas for Medical Sciences, Little Rock, AR, USA; 4Pfizer Inc, Groton, CT, USA; 5Pfizer Pharma GmbH, Berlin, Germany; 6Pfizer Ltd., Surrey, UK

Background: Patients with atopic dermatitis (AD) often have chronic hand eczema, a relapsing inflammatory disorder involving the skin of the hands. Abrocitinib, an oral once-daily selective Janus kinase 1 inhibitor, and dupilumab, an anti-IL4 receptor-α monoclonal antibody, are two systemic therapies approved for the treatment of moderate-to-severe AD. We evaluated the effects of abrocitinib and dupilumab in patients with moderate-to-severe AD with coexisting hand eczema.

Methods: Exploratory analyses were conducted for data from JADE DARE (NCT04345367), a double-blind Phase 3 trial of adult patients with moderate-to-severe AD who were randomly assigned 1:1 to receive 200mg abrocitinib (orally once daily) or 300mg dupilumab (subcutaneously once every 2 weeks). Patients received concomitant topical therapies to treat affected areas, including medium- or low-potency topical corticosteroids for active lesions. For patients with hand eczema, the subtype (allergic or irritant contact dermatitis, atopic, vesicular, or hyperkeratotic hand eczema, protein contact dermatitis/contact urticaria) was evaluated. The proportion of patients achieving a hand eczema Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1) with a ≥2-point improvement from baseline was assessed for the most affected hand over the 26-week treatment period. In addition, the extent of disease (finger/distal, finger/proximal, hand/dorsal, hand/ventral, wrist) and clinical signs (erythema, infiltration/papulation, vesicles, fissuring, scaling, edema) were evaluated for the most affected hand. Nominal P values were calculated for comparisons, which were not controlled for multiplicity.

Results: Of 362 patients in the abrocitinib 200mg group and 365 patients in the dupilumab 300mg group, 267 (74%) and 265 (73%) patients, respectively, had hand eczema, with most patients having chronic hand eczema (abrocitinib: 256 [96%]; dupilumab: 244 [92%]), which is defined as lasting for more than three months or relapsing at least 2 or more times per year. The extent, clinical signs, and subtypes of chronic hand eczema were similar in the two groups. Atopic hand eczema was the most common subtype (abrocitinib: 87%; dupilumab: 90%) followed by irritant contact dermatitis (abrocitinib: 14%; dupilumab: 13%) and hyperkeratotic eczema (abrocitinib: 11%; dupilumab: 7%). As early as Week 2, the proportion of patients with chronic hand eczema who achieved an IGA score of 0/1 for the most affected hand was significantly greater with abrocitinib (22% [95% CI: 17-27]) than with dupilumab (14% [95% CI: 9-18]; P≤0.05) and continued to increase through week 26 (abrocitinib: 74% [95% CI: 68-80]; dupilumab: 62 percent [95% CI: 55-68]; P≤0.01).

Conclusion: In patients with moderate-to-severe AD with coexisting chronic hand eczema, treatment with abrocitinib resulted in a greater proportion of patients achieving clear or almost clear skin on the most affected hand compared with patients treated with dupilumab; improvements with abrocitinib occurred rapidly and were sustained through 26 weeks. These results support the use of abrocitinib in patients with moderate-to-severe AD who had chronic hand eczema.

Funding: This study was funded by Pfizer Inc.

Disclosures: RB is an advisory board member, consultant, speaker, and/or Investigator for and receives honoraria and/or grant from Pfizer Inc., AbbVie, Arcutis, Arena Pharma, Asana BioSciences, Bellus Health, Boehringer Ingelheim, CARA, Dermavant, Eli Lilly and Company, EMD Serono, Galderma, Incyte, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Ralexar, RAPT, Regeneron, Sanofi Genzyme, and Sienna and is an employee and shareholder of Innovaderm Research.

MW has received honoraria for talks and expertise from AbbVie Deutschland GmbH & Co. KG, Actelion Pharmaceuticals Deutschland GmbH, Aimmune Therapeutics UK Limited, ALK-Abelló Arzneimittel GmbH, Allergopharma GmbH & Co.KG, Bencard Allergie GmbH, Biotest AG., DBV Technologies S.A., HAL Allergie GmbH, LEO Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Lilly Deutschland GmbH, Mylan Germany GmbH, Novartis AG, Regeneron Pharmaceuticals, and Stallergenes GmbH.

VYS is on the board of directors for the Hidradenitis Suppurativa Foundation (HSF), an advisor for the National Eczema Association, and a stock shareholder of Learn Health and has served as an advisory board member, investigator, speaker, and/or has received research funding from Pfizer Inc., AbbVie, Altus Lab/cQuell, Aristea Therapeutics, Boehringer Ingelheim, Burt’s Bees, Dermira, Eli Lilly and Company, Galderma, GpSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Polyfins Technology, Regeneron, Sanofi Genzyme, Skin Actives Scientific, SUN Pharma, Target-PharmaSolutions, and UCB.

FZ, GC, and TB are employees and shareholders of Pfizer Inc.

UK is an employee and shareholder of Pfizer Pharma GmbH.

CC is an employee and shareholder of Pfizer Ltd.

 

Efficacy of nemolizumab in atopic dermatitis: Rapid impact on EASI and SCORAD components

Presenters: Bouaziz JD,1 Pinter A,2 Alavi A,3 Alpizar S,4 Pulka G,5 Ahmad F,6 Chaouche K,7 Warren W,6 Piketty C7

Affiliations: 1Department of Dermatology, Paris VII Sorbonne Paris Cité University Assistance Publique – Hôpitaux de Paris, Paris, France; 2Department of Dermatology, Venereology, and Allergology, University Hospital Frankfurt am Main, Frankfurt am Main, GERMANY; 3Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, CANADA; 4Clinical Research Trials of Florida, Tampa, FL, USA; 5School of Medicine, Jagiellonian University Medical College, Cracow, POLAND; 6Galderma Laboratories, Fort Worth, TX, USA; 7Galderma, Rue d’Entre-Deux-Villes, Switzerland

Background: Nemolizumab is an interleukin-31 receptor inhibitor in Phase 3 for atopic dermatitis (AD). Common AD scores SCORing Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) help delineate action of nemolizumab.

Methods: Post-hoc analysis of Phase 2b data comparing nemolizumab 30mg (SC q4wk after a 60 mg loading dose, n=50) vs placebo (n=44) both plus steroids in patients with baseline EASI score ≥16. Analysis of SCORAD and EASI components, including SCORAD itch and sleep VAS scores.

Results: Demographics were similar between groups, including baseline SCORAD/EASI overall and component scores. Moderate disease in approximately 60 percent of subjects, severe in approximately 40 percent. By Week 16, LSMean decrease in total SCORAD score was 57.1% nemolizumab vs 28.2% placebo (P<0.001), with separation apparent at Week 1 (-26.7% vs -13.3% placebo, P<0.001). Week 16 SCORAD ratings of mild/absent for nemolizumab vs placebo were: dryness 55.3 percent vs. 38.7 percent; papulation 80.8 percent vs. 50.0 percent; erythema 68.0 percent vs 42.1 percent; excoriation 95.7 percent vs. 56.8 percent; lichenification 63.9 percent vs 52.3 percent; and oozing 97.9 percent vs 84.6 percent. Separation on SCORAD VAS was also seen by week 1 (P<0.001 for all timepoints). At Week 16, overall EASI score decreased 68.6 percent vs. 42.6 percent placebo; mean decreased erythema 64.1 percent vs. 36.4 percent; decreased excoriation 84.6 percent vs. 26.3 percent; decreased papulation 68.6 percent vs. 37.5 percent; and decreased lichenification 60.2 percent vs. 43.7 percent. Nemolizumab was safe with nasopharyngitis and respiratory infection most commonly seen.

Conclusion: Improvement of the clinical signs of AD as indicated by SCORAD components were apparent at Week 1 and increased through Week 16.

Funding: This study was funded by Galderma.

 

Greater skin clearance and itch improvement in atopic dermatitis are associated with the achievement of stringent patient-reported outcomes: Integrated analysis of three upadacitinib Phase 3 trials

Presenters: Silverberg JI,1 Deleuran M,2 Calimlim BM3, de Bruin-Weller MS4

Affiliations: 1Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; 2Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark; 3AbbVie Inc., North Chicago, IL, USA; 4National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, Netherlands

Background: It is not fully understood how different degrees of improvement in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient-reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, skin pain, quality of life (QoL), and emotional state. This post-hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL.

Methods: Data from three randomized, double-blind, placebo-controlled, Phase 3 trials in adults and adolescents with moderate-to-severe AD (Measure Up 1, Measure Up 2, and AD Up) were pooled. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30mg) or placebo once daily as monotherapy (Measure Up 1, Measure Up 2) or in combination with topical corticosteroids (AD Up). The proportion of patients achieving response at Week 16 were summarized by Eczema Area and Severity Index (EASI) improvement categories (<50, 50−<75, 75−<90, 90−<100, and 100), Worst Pruritus Numeric Rating Scale (WP-NRS) categories (0−1, 2−3, 4−6, 7−10), and composite EASI improvement and WP-NRS categories (EASI <90 and WP-NRS 2−10, EASI 90−100 and WP-NRS 2−10, EASI <90 and WP-NRS 0−1, and EASI 90−100 and WP-NRS 0−1). Outcomes included Patient-Oriented Eczema Measure (POEM) 0−2 (clear or almost clear eczema), Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain 0−1 (no/minimal skin pain), ADerm-SS 7-item total symptom score (TSS-7) 0−11 (no/minimal AD symptoms), Dermatology Life Quality Index (DLQI) 0−1 (no impact on QoL), Atopic Dermatitis Impact Scale (ADerm-IS) Sleep 0−3 (no/minimal impact of AD on sleep), ADerm-IS Daily Activities 0−2 (no/minimal impact of AD on daily activities), and ADerm-IS Emotional State 0−2 (no/minimal impact of AD on emotional state).

Results: A total of 2,392 patients from the three trials were included in the analysis. For all outcomes, response rates at Week 16 were incrementally greater at higher EASI improvement and WP-NRS itch reduction categories. Across all outcomes, response rates ranged from 32%−90% among the highest levels of skin clearance (EASI 90−100) and 59%−97% among WP-NRS 0−1 responders. Proportions of patients achieving response were highest among patients who achieved both EASI 90−100 and WP-NRS 0−1 (68%–99%).

Conclusion: Greater degrees of clinical responses, particularly EASI 90−100 and WP-NRS 0−1, are related to more robust improvements across multiple dimensions of AD, including itch, skin pain, sleep, and quality of life.

Disclosures: Silverberg JI has received honoraria as a consultant and/or advisory board member for AbbVie, AObiome, Arcutis, Alamar, Amgen, Arena, Arcutis, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma,GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, and Union; speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and his institution received grants from Galderma and Pfizer. Mette Deleuran has received research support, has consulting/advisory board agreements, and/or has received honoraria for lecturing from AbbVie, Eli Lilly, Leo Pharma, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Incyte, Kymab Ltd, La Roche Posay, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals, and Sanofi-Genzyme. Brian M. Calimlim is a full-time, salaried employee of AbbVie Inc. and owns AbbVie stock or stock options. Marjolein S. de Bruin-Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena, Aslan, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.

Funding: AbbVie provided funding for this study.

 

High-level responses across multiple domains in patients with atopic dermatitis treated with abrocitinib versus dupilumab: A post-hoc analysis of a Phase 3 randomized trial

Presenters: Armstrong AW,1 Blauvelt A,2 Gooderham MJ,3 Hong HCH,4 Zhang F,5 Feeney C,6 Clibborn C,6 Myers DE,7 Chan G5

Affiliations: 1Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Oregon Medical Research Center, Portland, OR, USA; 3SKiN Centre for Dermatology, Peterborough, ON, Canada; 4University of British Columbia, Vancouver, BC, Canada; 5Pfizer Inc., Groton, CT, USA; 6Pfizer Ltd., Tadworth, Surrey, UK; 7Pfizer Inc., Collegeville, PA, USA

Background: Moderate-to-severe atopic dermatitis (AD) is associated with a variety of signs and symptoms that affect patients’ quality of life (QoL). There is a need for effective therapies that can minimize multiple impacts of AD. 

Objective: Here, we examined the proportions of patients achieving high-level responses in two or three measures of treatment efficacy (skin clearance, reduction of itch, and improved QoL) with abrocitinib versus dupilumab in patients with moderate-to-severe AD.

Methods: This post-hoc analysis used data from JADE DARE (NCT04345367), a 26-week, randomized (1:1), Phase 3b, double-blinded, double-dummy trial designed to assess the efficacy and safety of oral abrocitinib (200mg once daily) versus subcutaneous dupilumab (300 mg every 2 weeks) in adults with moderate-to-severe AD receiving background medicated topical therapy. High-level responses were defined as achieving two or three of the following: ≥90% improvement in Eczema Area and Severity Index (EASI-90), Peak Pruritus Numerical Rating Scale (PP-NRS) score <2, and Dermatology Life Quality Index (DLQI) <2.

Results: Data were analyzed from 719 patients (abrocitinib, n=358; dupilumab, n=361). At Week 2, at least two high-level responses were achieved by 13 percent of abrocitinib-treated and 3 percent of dupilumab-treated patients; at Week 26, those proportions were 44 percent and 33 percent, respectively. Proportions of patients who achieved two or three high-level responses (EASI-90 + PP-NRS <2 ± DLQI <2; EASI-90 + DLQI <2 ± PP-NRS <2; PP-NRS <2 + DLQI <2 ± EASI-90) were larger with abrocitinib than with dupilumab, irrespective of domain combination: at Week 2, 5%-9% for abrocitinib and 0%-2% for dupilumab; at Week 26, 27%-33% for abrocitinib and 17%-22% for dupilumab. Proportions of patients achieving all three high-level responses at Week 2 were 4 percent (abrocitinib) and 0 percent (dupilumab); at Week 26, the proportions were 24 percent and 12 percent, respectively.

Conclusion: Patients with moderate-to-severe AD treated with abrocitinib were more likely to achieve at least two high-level responses, as early as Week 2, compared with patients treated with dupilumab. At Week 26, twice as many abrocitinib-treated patients achieved skin clearance, no itch, and no dermatologic impact on QoL as patients treated with dupilumab.

Funding: This study was funded by Pfizer Inc.

Disclosures: AWA has served as a research investigator and/or scientific advisor for Pfizer Inc., AbbVie, Boehringer Ingelheim, BMS, EPI Health, Incyte, LEO Pharma, UCB, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, and Regeneron. 

AB has served as a speaker, scientific adviser, and/or clinical study investigator for Pfizer Inc., AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, Vibliome, and Xencor. 

MJG has received grants, personal fees, honoraria, and/or nonfinancial support from Pfizer Inc., AbbVie, Amgen, AkrosPharma, Arcutis, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Novartis, Roche, Sanofi Genzyme, Regeneron, Sun Pharma, Dermavant, UCB, and Bausch Health (Valeant). 

HC-hH is a researcher, consultant, and/or advisor for Pfizer Inc., AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, DS Biopharma, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Lilly, MedImmune, Novartis, Regeneron, Roche, Sanofi Genzyme, and UCB. FZ, CF, CC, DEM, and GC are employees and stockholders of Pfizer Inc.

 

Incremental improvements after switching from dupilumab (DUPI) to upadacitinib (UPA) in the heads up open-label extension (OLE) study

Presenters: Prajapati VH,1 Glick B,2 Spelman L,3 Nart IF,4 Calimlim B,5 Ladizinski B,5 Wu T,5 Liu Y,5 Davis J,5 Aydin H,5 Ehst B6

Affiliations: 1University of Calgary, Skin Health & Wellness Centre, Dermatology Research Institute, and Probity Medical Research, Calgary, AB, Canada; 2Glick Skin Institute, Margate, FL, USA; 3Veracity Clinical Research, Brisbane, Queensland, Australia and Probity Medical, Ontario, Canada; 4Hospital Universitari de Bellvitge, University of Barcelona, Barcelona, Spain; 5AbbVie Inc., North Chicago, IL, USA; 6Oregon Medical Research Center, Portland, OR, USA.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.

Objective: Heads Up was a Phase 3b, randomized, double-blind, double-dummy clinical trial comparing the efficacy and safety of DUPI vs UPA in adults with moderate-to-severe AD over 24 weeks.

Methods: In the Heads Up OLE, all patients received UPA 30mg orally once daily for an additional 52 weeks. This analysis characterized the incremental changes in Eczema Area and Severity Index (EASI) and Worst Pruritus Numerical Rating Scale (WP-NRS) scores during the Heads Up OLE in patients who switched from DUPI to UPA after 24 weeks of DUPI treatment.

Results: Among patients who did not achieve ≥75% improvement in EASI (EASI 75) with DUPI, 75.0 percent and 87.5 percent achieved EASI 75 with UPA after Week 4 and Week 16, respectively, while 0 percent and 2 percent of patients who achieved EASI 75 with DUPI did not maintain this response with UPA. Similar results were observed for EASI 90. Among patients with WP-NRS ≥4 at baseline who did not achieve WP-NRS improvement ≥4 with DUPI, 56.6 percent and 57.7 percent achieved WP-NRS improvement ≥4 with UPA after four and 16 weeks, respectively, while 3.7 percent and 8.8 percent of patients who achieved WP-NRS improvement ≥4 with DUPI did not maintain this response with UPA.

Conclusion: Most patients with a suboptimal response (EASI <75 and WP-NRS improvement <4) to DUPI experienced greater skin clearance and itch reduction after switching to UPA. These are the first observations reported in patients receiving UPA following treatment with DUPI.

 

Lebrikizumab treatment improves four EASI clinical signs over 16 weeks in moderate-to-severe atopic dermatitis

Presenters: Simpson E,1 Hong HCH,2 Eyerich K3 Thyssen JP,4 Shahriari M,5 Atwater AR,6 Elmaraghy H6, Agell H,7 Chen S,8 Zhong J,9 de Bruin-Weller M,10

Affiliations: 1Oregon Health & Science University, Portland, USA; 2Department of Dermatology and Skin Science, University of British Columbia, British Columbia, CA; 3Department of Dermatology and Venerology, Medical Center, University of Freiburg, DE; 4Bispebjerg Hospital, University of Copenhagen, Copenhagen, DK; 5Yale University School of Medicine, New Haven, USA; 6Eli Lilly and Company, Indianapolis, USA; 7Almirall, A.S., Barcelona, ESP; 8Tigermed, New Jersey, USA; 9IQVIA, North Carolina, USA; 10University Medical Center Utrecht, Utrecht, NL

Background: Some areas of the body, and some individual signs may be more resistant to treatment in atopic dermatitis (AD).

Objective: The purpose of this analysis was to determine the efficacy of lebrikizumab for AD across four clinical signs by anatomical region in three Phase 3 clinical trials.

Methods: ADvocate1 and ADvocate2 compared monotherapy lebrikizumab 250mg every two weeks (LEBQ2W) versus placebo for 16 weeks. Patients enrolled in ADhere used topical corticosteroids in addition to LEB Q2W or placebo for 16 weeks. A component of the Eczema Area and Severity Index (EASI) rates the severity of four key clinical signs of AD, in four body regions: erythema, edema/papulation, excoriation and lichenification. The lesion severity scale ranges from 0 to 3, where zero is no involvement and three is severe involvement. This analysis reports mean baseline severity and least squares mean percent change from baseline (%CFB) for each clinical sign for each body region. Data after rescue therapy usage or discontinuation of treatment were considered as missing and were handled using MMRM. Analyses are post-hoc without multiplicity control.

Results: The mean baseline values for severity of EASI signs by body regions are consistent across all three studies. For ADvocate1, head/neck region, a statistically significant improvement in %CFB in all four clinical signs was seen as early as Week 2 of treatment with LEBQ2W compared to placebo, (p<0.001). Similarly, for trunk, upper extremities and lower extremities, a statistically significant improvement in %CFB for all clinical signs was seen from Week 2 through Week 16 (p<0.01). For ADvocate2, head/neck region, statistically significant improvement in %CFB was seen as early as Week 2 for edema/papulation, excoriation, and lichenification, and early as Week 4 for erythema with LEBQ2W compared to placebo (p<0.05). For trunk and upper extremities, statistically significant improvement in %CFB for all four signs was seen as early as Week 2 versus placebo (p<0.05). For lower extremities, improvement in %CFB is seen by Week 4 for erythema, edema/papulation, and lichenification (p<0.001) and by Week 2 for excoriation (p<0.001). For ADhere, in the head/neck region statistical significance in %CFB was first seen at Week 6 for erythema and lichenification (p<0.05), for edema/papulation at Week 4 (p<0.05), and excoriation at Week 2 (p<0.05). For the trunk region, statistical significance was first seen at Week 4 (p<0.05) for erythema, edema/papulation, and excoriation. Statistical significance was first seen as early as week 6 for lichenification (p<0.05). For upper and lower extremities, statistical significance was first seen at Week 4 for edema/papulation (p<0.02) and excoriation (p<0.003), Week 6 for erythema (p<0.02) and Week 8 for lichenification (p<0.02). All clinical signs across all body regions showed statistical significance at Week 16 in all three studies (p<0.05).

Conclusion: Lebrikizumab both in monotherapy and in combination with topical corticosteroids consistently reduced AD severity across four clinical signs and across four body regions, compared to placebo.

 

Real-world psychosocial and economic burden of atopic dermatitis related to disease severity and use of systemic therapy: Results from a multicountry study

Presenters: Aoki V,1 Eyerich K,2 Schmid-Grendelmeier P,3 Gkalpakiotis S,4 Teixeira HD,5 Takemoto S,6 Calimlim BM,5 Chen, SH,7 Sancho C,8 Silvestre JF9

Affiliations: 1Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil; 2Department of Dermatology and Venereology, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany; 3Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; 4Department of Dermatovenereology, Third Faculty of Medicine, Charles University, and University Hospital Kralovske Vinohrady, Prague, Czech Republic; 5AbbVie Inc., North Chicago, USA; 6AbbVie GK, Tokyo, Japan; 7Tigermed-BDM Inc., Somerset, USA; 8AbbVie Madrid, Spain; 9Department of Dermatology, Hospital General Universitario de Alicante, Alicante, Spain

Background: MEASURE-AD was a cross-sectional 28-country study of patients with AD. Primary study findings have been reported. In this analysis, we describe the psychosocial and economic burden of AD relative to patients’ disease severity and current systemic therapy use.

Methods: MEASURE-AD recruited patients with AD 12 years or older between December 2019 and December 2020 from Western Europe, Eastern Europe, Middle East, Asia, Canada, and Latin America. Mental health status was characterized by the 12-Item Short Form Health Survey Mental Component Summary (SF-12 MCS) score and anxiety and depression were characterized by the proportions of patients with Hospital Anxiety and Depression Scale (HADS) anxiety (HADS-A) and depression (HADS-D) subscale scores of eight or more. Financial cost due to AD was characterized by the median patient-reported cost of healthcare-related expenses and everyday necessities related to AD. Results were presented by AD severity level (Eczema Area and Severity Index [EASI] of clear [0], mild [0.1-5.9], moderate [6.0-22.9], and severe [23.0-72.0]) and current systemic therapy use (yes, no). Differences were analyzed using Kruskal-Wallis tests and chi-square tests, as appropriate. Here we report analyses for adults (age ≥18 years).

Results: Among 1,434 adult patients with AD, mean age was 39.1 years, 52.2 percent (n=748) were men, and 60.5 percent (n=868) were employed. Of 1,428 patients with EASI data, AD severity was rated as clear, mild, moderate, and severe for 5.7 percent, 25.5 percent, 43.5 percent, and 25.4 percent, respectively. Patients with worse disease severity had significantly worse mental health status, were much more likely to meet cut-off scores for depression and anxiety, and had higher financial costs. Among the 1,434 patients, 813 (56.7%) were currently receiving systemic therapy, most commonly dupilumab (n=468, 57.6%), systemic corticosteroids (n=146, 18.0%), methotrexate (n=124, 15.3%), or cyclosporine (n=122, 15.0%). Patients not currently receiving systemic therapy had significantly worse mental health status, were more likely to meet cut-off scores for anxiety or depression, and had higher financial costs compared with patients receiving systemic therapy.

Conclusion: This analysis of more than 1,400 adults with AD, demonstrated that a psychosocial and economic burden exists among patients with AD. The burden is higher for patients with more severe disease and for those not treated with systemic therapies. Overall, a significant unmet need remains for effective treatments to improve patients’ psychosocial outcomes and reduce the economic burden of AD.

 

Rocatinlimab demonstrates improvements in head and neck atopic dermatitis in patients with moderate-to-severe disease in a Phase 2 trial

Presenters: Guttman-Yassky E,1 Esfandiari E,2 Chong C,2 Matsui T,3 Mano H3

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Kyowa Kirin, Marlow, UK; 3Kyowa Kirin, Tokyo, Japan

Background: Head and neck (H&N) dermatitis, a clinical variant of atopic dermatitis (AD), negatively impacts quality of life. The H&N region can be vulnerable to environmental triggers and harder to treat than other body parts. AD is associated with high rates of allergic and irritant contact dermatitis especially on the face. Increased tendency to Malassezia proliferation, mainly localized in the sebaceous H&N region, may also play a role, and exacerbation or initiation of H&N dermatitis is associated with inhibition of interleukin-4 receptor. The immune response in AD leads to transient expression of OX40 in skin lesions, potentiating expansion, differentiation, and survival of pathogenic T cells. Rocatinlimab (AMG-451/KHK4083) is a first-in-class anti-OX40 monoclonal antibody that inhibits and reduces the number of OX40+ pathogenic T cells responsible for driving systemic and local AD inflammatory responses. Results from a randomized Phase 2b study in adults with moderate-to-severe AD showed significant improvement in efficacy parameters compared with placebo.1 Here, we describe treatment response to rocatinlimab in an H&N dermatitis subpopulation from a Phase 2 trial in patients with moderate-to-severe AD (NCT03703102).

Methods: Post-hoc analysis of 219 patients with baseline H&N Eczema Area and Severity Index (EASI) score more than 1.5 receiving subcutaneous rocatinlimab (150 or 600 mg every 4 weeks [Q4W], 300 or 600 mg every 2 weeks [Q2W]) for 36 weeks), or placebo (Weeks 0–18, followed by rocatinlimab 600 mg Q2W [Weeks 18–36]), and a 20-week off-drug follow-up period (until Week 56). We reported disease burden by baseline anatomical H&N region and assessed the impact of rocatinlimab on H&N EASI score. This analysis evaluated the least-squares mean percentage change from baseline up to Week 56 in H&N EASI score (calculated by severity score of [Erythema + Edema/Papulation + Excoriation + Lichenification] at H&N region*Area × 0.1).

Results: Baseline characteristics were balanced across cohorts. H&N EASI scores improved significantly across all four rocatinlimab cohorts versus placebo at Week 16 (150 mg Q4W: –43.9%, 600mg Q4W: –59.4%, 300mg Q2W: –60.3%, 600mg Q2W: –65.2% versus placebo: –16.7%; P<0.001 for all rocatinlimab doses except 150mg Q4W [P=0.008]) similar to reported improvements in total EASI score (primary endpoint). Most patients maintained responses even after treatment discontinuation. Patients who switched from placebo to rocatinlimab 600mg Q2W at Week 18 demonstrated improved H&N EASI scores in line with two active treatment cohorts. No new safety signals were observed, including no new H&N lesions.

Conclusion: In patients with H&N dermatitis inadequately controlled with topical therapy, all rocatinlimab doses led to greater improvements in H&N EASI score than placebo at Week 16. Durability of response with rocatinlimab is unique among current AD therapies, potentially reflecting the unique mechanism of action, and may be suggestive of disease modification. This is the first evidence of an anti-OX40 monoclonal antibody improving disease severity in patients with hard-to-treat H&N dermatitis. Rocatinlimab thus represents a potential novel treatment option.

Funding: This study was funded by Kyowa Kirin Co., Ltd.

Disclosures: EGY: AbbVie, Almirall, Amgen, AnaptysBio, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, BI, BMS, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Innovaderm, Janssen, Kyowa Kirin, Leo Pharma, Novartis, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB, and Ventyx Biosciences – Grants and/or consultant. 

EE, CC, TM, and HM are employees at Kyowa Kirin.

 

Safety of tralokinumab in pediatric patients aged 12–17 with moderate-to-severe atopic dermatitis: results from the Phase 3 ECZTRA 6 trial

Presenters: Wollenberg A,1 Cork M,2 Flohr C,3 Bewley A,4 Blauvelt A,5 Hong CH,6 Imafuku S,7 Schuttelaar MLA,8 Simpson EL9, Soong W,10 Arlert P,11 Lophaven K,11, Kurbasic A,11 Soldbro L,11 Vest NS,11 Paller A12

Affiliations: 1Ludwig Maximilian University of Munich, Germany; 2The University of Sheffield and Sheffield Teaching Hospitals, UK; 3Guy’s & St Thomas’ NHS Foundation Trust and King’s College London, UK; 4Barts Health NHS Trust, UK; 5Oregon Medical Research Center, USA; 6University of British Columbia, Canada; 7Fukuoka University, Japan; 8University of Groningen, The Netherlands; 9Oregon Health & Science University, USA; 10Allervie Health-Alabama Allergy & Asthma Center, USA; 11LEO Pharma, A/S, Denmark; 12Northwestern University, USA

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a substantial disease burden. Limited treatment options are available for pediatric patients with moderate-to-severe disease. In the Phase 3 ECZTRA 6 trial (NCT03526861), tralokinumab was effective and well tolerated in patients aged 12 to 17 years with AD. Here, we report longer-term safety data from this trial.

Methods: Patients with moderate-to-severe AD were randomised to tralokinumab 150mg or 300mg or placebo every two weeks (Q2W) during the initial Phase (Weeks 0–16), then further treated until Week 52. Week 16 responders were dosed either with 150mg or 300mg Q2W or Q4W and non-responders (open-label) were dosed with 300mg Q2W for Weeks 16–52. Safety endpoints included number of non-serious and serious adverse events (AE and SAE).

Results: Tralokinumab was well tolerated in pediatric patients. At Week 16, the most frequent AEs (tralokinumab pooled vs placebo) were upper respiratory tract infection (URTI) (9.7 vs 4.3%), viral URTI (15.9 vs 8.5%), atopic dermatitis aggravated (10.3 vs 12.8%), injection site reaction (4.1 vs 0%), asthma (1.5 vs 5.3%) and headache (5.6 vs 3.2%). More patients in the tralokinumab 150mg group had atopic dermatitis aggravated (13.3%) than in the 300mg group (7.2%). The number of patients with conjunctivitis was low in the pooled tralokinumab and placebo arms (3.6 vs 2.1%). For Weeks 16–52, the types and frequencies of AEs were similar to the initial phase. Numbers of SAEs were low throughout the 52 weeks, with 11 events reported; only one of which was considered related to tralokinumab by the investigator. No clinically relevant changes in laboratory parameters were observed.

Conclusion: Tralokinumab was well tolerated in pediatric patients aged 12 to 17 years with moderate-to-severe AD. Patients receiving the 300mg Q2W dose had numerically lower rates of AD exacerbation than the 150mg Q2W group, and the rate of conjunctivitis was generally low. The safety profile of tralokinumab in this paediatric population was consistent with that of adults.

Funding: Funding was provided by LEO Pharma A/S .

Disclosures: AW has received grants, personal fees, or nonfinancial support from AbbVie, Aileens, Almirall, Beiersdorf, Bioderma, Chugai, Galapagos, Galderma, Hans Karrer, LEO Pharma, Lilly, L’Oreal, Maruho, MedImmune, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis.

CF is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (Clinicaltrials.gov NCT03270566) trials as well as the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a Principal Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). He also leads the EU Trans-Foods consortium. His department has received funding from Sanofi-Genzyme for skin microbiome work.

AB has served as a speaker/received honoraria from AbbVie and UCB, served as a scientific adviser/received honoraria from AbbVie, Abcentra, Aligos, Almirall, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, EcoR1, Eli Lilly and Company, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator/institution has received clinical study funds from AbbVie, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma.

WS has served on the advisory board and received research grants from Abbvie, LEO Pharma, Genentech, Inc., Teva, Novartis, and Pfizer; served on the advisory board, received research grants, and was a speaker for Amgen, AstraZeneca, Regeneron, Sanofi, and GlaxoSmithKline; received research grants and was a speaker for Optinose; received research grants from Aimmune, Avillion, Galderma, Gossamer Bio, 3M, and LEO Pharma.

SI is a researcher, consultant, or speaker for Abbvie, Amgen, Celgene, DaiichiSankyo, Eisai, KyowaKirin, Lilly, Taihoyakuhinkogyo, TanabeMitsubishi, Tsumura, Torii, Maruho, Novartis, LEO Pharma, and Janssen.

CHH is a researcher, consultant, and/or advisor for AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Celgene, Dermavant, Dermira, DS Biopharma, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, and UCB.

MLA Schuttelaar has served on advisory boards for Sanofi Genzyme, Pfizer, LEO Pharma, Eli Lilly, Galderma, and Abbvie; as an investigator for AbbVie, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Galderma; as a consultant for Regeneron Pharmaceuticals, Inc.; has received research grants from Sanofi Genzyme and Novartis.

PA, AK, LS, KL and NSV are employees of LEO Pharma A/S.

MC has served as a clinical trial investigator for Astellas, Galapagos, Johnson & Johnson, LEO Pharma, La Roche-Posay, MSD, Novartis, Perrigo, Regeneron, Sanofi Genzyme, and Stiefel; has served as an advisory board member, consultant, and/or invited lecturer for Pfizer Inc., Amgen, Astellas, Bayer, Johnson & Johnson, LEO Pharma, L’Oréal, MSD, Novartis, Regeneron, Sanofi Genzyme, Stiefel, and Unilever; has received honoraria from Astellas, Johnson & Johnson, LEO Pharma, Novartis, Regeneron, Sanofi Genzyme, and Stiefel; and has received research funding from Bayer.

AB has been a consultant for and received consultancy fees or travel bursaries from AbbVie, Almiral, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Sanofi, and UCB Pharma.

ES is a consultant and investigator for Regeneron/Sanofi, Dermira, Menlo Pharmaceuticals, Lilly, Abbvie, Genentech, Medimmune, GSK, LEO Pharma, Celgene, and Pfizer.

AP has served as an investigator for AbbVie, Anaptysbio, Incyte, Janssen, KrystalBio, LEO Pharma, Regeneron, and UCB, received honorarium for consultancy from AbbVie, Abeona, Almirall, Anaptysbio, Arena, Azitra, BiomX, Boehringer Ingelheim, Castle Biosciences, Catawba, Dermira, Exicure, Forté, Kamari, LEO Pharma, Lilly, LifeMax, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Seanergy, and UCB, and served on a Data Safety Monitory Board for AbbVie, Bausch, Galderma, and Novan.

 

Tapinarof cream 1% once daily for the treatment of extensive atopic dermatitis in adolescents and children: 4-week maximal-use trial

Presenters: Paller A,1 Hebert AA,2 Jett JE,3 Brown PM,3 Rubenstein DS,3 Piscitelli SC3

Affiliations: 1Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2McGovern School of Medicine and Children’s Memorial Hermann Hospital, UTHealth McGovern, Houston, TX, USA; 3Dermavant Sciences, Inc., Morrisville, NC, USA

Background: Atopic dermatitis (AD) is a chronic, relapsing and remitting inflammatory skin disease, characterized by intense pruritus and eczematous lesions. AD can substantially impact patients’ sleep and quality of life. There is a need for efficacious, non-steroidal topical therapies for AD, without restrictions relating to duration, extent of use, and application sites

Objective: To present a 4-week, maximal-use AD trial design and patient baseline characteristics, and to assess the safety, tolerability, PK, and efficacy of tapinarof cream 1% QD in adolescents and children with extensive AD in the 4-week, maximal-use trial.

Methods: In this Phase 2a, multicenter, open-label trial (NCT05186805), adolescents and children with extensive AD received tapinarof cream 1% QD for 27 days. Patients or caregivers were instructed to apply a thin layer of tapinarof cream, sufficient to cover each lesion. Tapinarof PK was assessed at Days 1 (baseline) and 28. The screening blood sample was used for baseline pre-dose PK assessment if the patient was enrolled. Eligible patients completing this trial had the option to enroll in an open-label, long-term extension trial (NCT05142774) to receive up to an additional 48 weeks of tapinarof treatment.

Results: Overall, 36 patients were enrolled at nine sites in the US and Canada. Equal proportions of patients (33.3% [12/36]) were young children (2–6 years), children (7–11 years), and adolescents (12–17 years). Most patients (77.8%) across the three groups had a vIGA-ADTM score of three (moderate). Overall mean (standard deviation [SD]) EASI score was 23.8 (9.2), with a range of 8.2 to 49.6 indicating moderate-to-severe AD. Overall mean (SD)% BSA affected was 42.8 percent (15.1%), with a range of 26%–90%.

Conclusion: Tapinarof cream 1% QD demonstrated significant efficacy versus vehicle and was well tolerated in adolescents and adults with moderate-to-severe AD. Tapinarof cream 1% has shown minimal systemic absorption in adults with AD or psoriasis, even with extensive BSA affected of up to 46 percent.

Funding: Dermavant Sciences, Inc. provided funding for this study.

Disclosures: DAP is an investigator (without personal compensation) for AbbVie, AnaptysBio, Dermavant Sciences Inc., Eli Lilly, Incyte, Janssen, Krystal, Regeneron, and UCB Pharma, a consultant (with honoraria) for AbbVie, Acrotech, Almirall, Amgen, Amryt, Arcutis, Arena, Azitra, BioCryst, BiomX, Boehringer Ingelheim, Botanix, Bridgebio, Castle Biosciences, Catawba, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Kamari, Leo, Novartis, Pfizer, Pierre Fabre, RAPT, Regeneron, Sanofi/Genzyme, Seanergy, UCB Pharma, Union, and on the Data Safety Monitoring Board for AbbVie, Abeona, Bausch, Bristol Myers Squibb, Galderma, Inmed, and Novan. 

AAH has received grants/honoraria/ research support from AbbVie, Almirall, Arcutis, Dermavant Sciences Inc., GSK (as part of a Data Safety Monitoring Board), Incyte, LEO Pharma, Mayne, Novan, and Verrica. 

JEJ, PMB, DSR, and SCP are employees of Dermavant Sciences, Inc., with stock options.

 

Three years of tralokinumab treatment provides long-term disease control as demonstrated by clinically meaningful outcomes in moderate-to-severe atopic dermatitis

Presenters: Warren RB,1 Reich K,2 Simpson E,3 Langley R,4 Costanzo A,5 Saeki H,6 Almgren P,7 Vacko E,7 Carlsson A,7 Gooderham M,8 Deleuran M,9 Silvestre JF,10 Weidinger S,11 Blauvelt A12

Affiliations: 1The University of Manchester, Manchester, UK; 2University Medical Center Hamburg-Eppendorf, Hamburg, DE; 3Oregon Health & Science University, Portland, OR, USA; 4Dalhousie University, Halifax, Nova Scotia, CA; 5Humanitas University, Milano, IT; Humanitas Research Hospital IRCCS, Milano, IT; 6Nippon Medical School, Tokyo, JP; 7LEO Pharma A/S, Ballerup, DK; 8SKiN Centre for Dermatology, Peterborough; Queen’s University, Kingston; Probity Medical Research, Waterloo, ON, CA; 9Aarhus University Hospital, Aarhus, DK; 10Hospital General Universitario de Alicante, Alicante, ES; 11Hospital Schleswig-Holstein, Campus Kiel, Kiel, DE; 12Oregon Medical Research Center, Portland, OR, USA

Background: Tralokinumab, an interleukin-13 inhibitor, is approved for adults with moderate-to-severe AD. Tralokinumab was well-tolerated and provided significant improvements in AD severity up to 52 weeks of treatment. ECZTEND (NCT03587805), an ongoing, open-label, 5-year extension trial, is assessing the safety and efficacy of tralokinumab plus optional topical corticosteroids (TCS) after parent trials (PTs). We report a post-hoc subgroup analysis of patients who completed three years of tralokinumab treatment.

Methods: 347 participants received the approved dose of subcutaneous tralokinumab 300mg every two weeks for three years (1 year in a PT plus 2 years in ECZTEND), with optional TCS in ECZTEND as of the data cutoff. Endpoints included EASI-75/90, IGA 0/1, (clear/almost-clear skin), and EASI ≤7 (mild disease) at Week 104. Patient-reported outcome measures included worst weekly itch NRS and DLQI. The overlap of patients achieving clinically relevant outcomes was assessed (EASI≤7/itch NRS≤4/DLQI≤5). Sensitivity analyses to address missing data in ECZTEND (but not the PTs) included: (1) last observation carried forward (LOCF) for intermittent missing data and (2) modified non-responder imputation (mNRI) which sets discontinuation due to adverse events (AEs) or lack of efficacy as non-response and uses LOCF for other missing data. A summary of AEs will also be reported.

Results: EASI-75 [% (n/N)] and EASI-90 [% (n/N)] was achieved in 76 percent (263/347) and 54 percent (186/347) of patients, respectively. IGA 0/1 and EASI ≤7 was achieved in 44 percent (151/347) and 75 percent (261/347) by mNRI, respectively. 93 percent [n/N 254/274, as observed (AO)]/ 84 percent (by mNRI) of patients achieved clinically meaningful improvement in at least one measure (EASI≤7, itch NRS≤4, or DLQI≤5) after three years of tralokinumab treatment. Fifty-eight percent (156/270, AO)/51% (by mNRI) of patients achieved clinically meaningful improvements of all three outcomes (EASI ≤7/itch NRS ≤4/DLQI ≤5). The safety profile was favorable and consistent with the PTs and the overall ECZTEND population (n=1442), with no new safety signals arising with continued tralokinumab.

Conclusion: In patients with moderate-to-severe AD treated with tralokinumab for three years, robust and clinically meaningful improvements were observed in AD signs and symptoms. These data, in combination with the favourable safety profile, support tralokinumab as an efficacious and well-tolerated treatment option for long-term disease control in patients with moderate-to-severe AD.

 


CUTANEOUS ONCOLOGY


 

Clinical performance of novel elastic scattering spectroscopy (ESS) in detection of skin cancer: a blinded, prospective, multi-center clinical trial

Presenters: Merry SP,1 Chatha K,4 Croghan I,1 Nguyen VL,4 McCormick B,2 Leffell D3

Affiliations: 1Mayo Clinic, Rochester, MN; 2Hampton Family Practice, Hampton, VA; 3Yale School of Medicine, New Haven, CT; 4DermaSensor, Inc., Miami, FL

Background: Skin cancer incidence is growing world-wide as the population ages. However, primary care providers (PCPs) have demonstrable difficulty in identifying skin lesions which should be biopsied, and access to dermatology specialty care is limited. The objective of this study was to investigate the sensitivity and the specificity of a new skin cancer detection device which uses elastic scattering spectroscopy (ESS) in evaluating skin lesions and to compare the device sensitivity to that of primary care physicians.

Methods: A blinded, prospective, multi-center study was performed at 22 primary care study sites across the US (18) and Australia (4). A total of 1005 patients with 1579 lesions suggestive of skin cancer were enrolled and lesions were scanned with this new ESS device. Both patients and providers were blinded to the device results. Clinical care was provided according to standard of care for suspicious skin lesions. All lesions enrolled were biopsied. Statistical analyses included standard diagnostic test parameters of the device for detecting skin cancer and dermatopathologist discordance as well as subgroup analyses of clinical interest.

Results: Of the 1,005 patients studied, 51.4 percent were females with an average age of 59 years; the majority were Fitzpatrick Skin Type III (35.0%). On average patients had one (65.4%) or two (20.6%) lesions, for a total of 1579 lesions. Prior to biopsy, PCPs predicted 822 of the lesions would be “malignant” of which they predicted 322 would be “melanoma” and predicted 757 would be “benign” though all were concerning enough to biopsy. Dermatopathology found 224 high risk lesions including 48 melanomas, 90 basal cell carcinomas and 86 squamous cell carcinomas. PCPs had an overall sensitivity of 83.0 percent for predicting cancer. The ESS device had an overall sensitivity of 95.5 percent for detecting malignancy (sensitivity of 87.5 percent for melanoma, 97.8 percent for BCCs and 98.7% for SCCs, respectively). The overall specificity of the device was 20.7 percent. Use of the device could have improved PCP sensitivity from 83.0 to 95.5 percent (p<0.0001).

Conclusion: The ESS device demonstrated high sensitivity in detecting skin cancer when compared to the gold standard of dermatopathology. PCPs can confidently use this device to inform decisions about those skin lesions to biopsy or refer and those to monitor. This sensitive, simple, non-invasive, automated, point-of-care diagnostic tool is likely to fill a well-recognized void in PCP dermatologic care.

Funding: This study was funded by DermaSensor, Inc.

Disclosures: Dr. Leffell is a Scientific Advisory Board member for DermaSensor, and Drs. Nguyen and Chatha are employees of DermaSensor, Inc.

 

Clinical utility of an elastic scattering spectroscopy device in assisting primary care physician’s detection of skin cancers

Presenters: Seiverling EV,1 Agresta T,2 Cyr P,3 Caines L,4 Nguyen VL,6 Chatha K6; Siegel DM5

Affiliations: 1Tufts University School of Medicine, Boston, MA; 2University of Connecticut School of Medicine, Farmington, CT; 3Maine Medical Partners Family Medicine, Portland, ME; 4UConn Health, Farmington, CT; 5SUNY Downstate Health Sciences University, Brooklyn, NY; 6DermaSensor, Inc., Miami, FL

Background: Elastic-Scattering Spectroscopy (ESS), an optical tissue sampling technique, distinguishes between normal and abnormal tissue in vivo without the need to remove tissue. A handheld device that employs ESS and artificial intelligence was developed as an adjunctive tool for primary care practitioners (PCPs), to aid in their management of lesions suspicious for skin cancer. The aim of this study was to assess and compare the diagnosis and management performance of PCPs with and without the use of the handheld ESS device in detecting skin cancer.

Methods: An accompanying clinical validation study was performed in which 1579 lesions from 1005 patients were assessed with the ESS device. In this clinical utility study, 108 PCPs evaluated 50 skin lesions (25 malignant, 25 benign), with and without ESS device output. For each case, PCPs provided diagnosis, management decision, and level of confidence of management decision. Sensitivity and specificity of PCP diagnostic and management with and without the device output were calculated.

Results: PCP participants included board-certified internal and family medicine physicians (IM: 48.1%, FM: 51.9%) with an even distribution of years in practice (range: 1-21+ years). Management sensitivity increased significantly from 82.0 to 91.4 percent (p=0.003) with device output. Diagnostic sensitivity increased significantly from 71.1 to 81.7 percent with device output (p=0.008). Associated specificities decreased, from 60.9 to 54.7 percent (p=0.190) for diagnosis and from 44.2 to 32.4 percent (p=0.026) for referrals. Physicians reporting high confidence in their assessments increased from 73.0 to 81.6 percent (p<0.0001) with device output. Overall diagnostic performance (i.e. Area Under the Curve) increased from 0.685 to 0.727.

Conclusion: Use of the ESS device by PCPs significantly improved diagnostic and management sensitivity, with clinically acceptable decreases in associated specificities. The findings suggest the availability of the ESS device results improves PCP skin cancer detection and confidence in skin lesion evaluation and management.

Funding: This study was funded by DermaSensor, Inc.

Disclosures: Drs. Nguyen and Chatha are employees of DermaSensor, Inc.

 

Differentiating seborrheic keratoses with a blue-white veil from melanomas

Presenters: Pastore LM,1,2 Nazir ZH,1,3 Xu JR,1 Dusza SW,1 Braun R,4 Bravo C,5 Rabinovitz HS,6 Marghoob AA1

Affiliations: 1Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; 2Cooper Medical School of Rowan University, Camden, New Jersey; 3Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York; 4Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; 5Department of Dermatology, Pontificia Universidad Javeriana, Bogota, Colombia; 6Skin and Cancer Associates, Plantation, Florida

Background: A blue-white-veil (BWV) is common to pigmented, acanthotic seborrheic keratoses (SK) and pigmented invasive melanoma (MM).1 The histopathology correlates of the BWV in SK and in MM may provide clues to assist in differentiating the BWV in these lesions. In MM, the BWV is due to the Tyndall effect with pigmented melanocytes in the deeper dermis producing the blue hue and the overlying orthokeratosis resulting in the whitish veil.2 Furthermore, when the BWV in these MMs is viewed with polarized light, shiny white structures (SWS) will usually be observed due to matrix/stromal alterations.2 The presence of a BWV in SK is also due to the Tyndall effect; however in these lesions it’s the presence of pigment within an acanthotic epidermis which creates the effect.2 In such acanthotic SKs the presence of milia and comedo openings is common and the presence of SWS with polarized light is uncommon.3 We hypothesized that the presence of milia and comedo within the BWV and the absence of MM specific structures will indicate a diagnosis of SK. While SWS within the BWV will indicate MM.

Methods: This retrospective case-control study, selected 150 consecutively biopsied SKs and MMs that exhibited a BWV from patients at Memorial Sloan Kettering Cancer Center and dermatology practices in Plantation, Florida and Zurich, Switzerland. A double blinded expert dermoscopist annotated for the presence of structures present within or outside the borders of the BWV. MM specific structures included: atypical pigment network, angulated lines, negative network, atypical streaks, atypical dots and globules, atypical blotch, regression structures, structureless area, SWS, and atypical vascular structures. SK specific structures included: milia, comedo, and gyri/sulci.

Results: We identified 48 SKs and 102 MMs with a BWV. There were 40 lesions with milia and comedo inside the BWV. Of these cases, there were 17 lesions with no MM specific structures, all of which proved to be SKs (100%). Within that same group of 40 lesions, there were 23 cases where at least one MM specific structure was present; 18 of the lesions were SKs (78.3%) and five were MM (21.7%). Additionally, we found 55 lesions with SWS in the BWV. Irrespective of milia, comedo, or other melanoma specific structures, 50 of these lesions were MMs (90.9%) and five were SKs (9.1%).

Conclusion: The presence of milia and comedo within the BWV in the absence of MM specific structures, may significantly improve the diagnostic specificity of SK and result in fewer unnecessary biopsies. If any MM specific structures are seen, despite the presence of milia and comedo inside the BWV, a biopsy remains necessary as 21.7 percent of these lesions proved to be MM. In contrast, SWS present within the BWV (irrespective of the presence of any other structures) strongly suggests MM with almost 91 percent of such lesions proving to be malignant. Limitations to our findings includes small sample size, selection bias, lack of a control group, and limited number of reviewers.

 

Hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200mg daily: Results from the 42-month BOLT study

Presenters: Migden M,1 Guminski A,2-4 Gutzmer R,5 Loquai C,6 Squittieri N,7 Foley P8-10

Affiliations: 1University of Texas MD Anderson Cancer Center, Departments of Dermatology, Division of Internal Medicine, and Head and Neck Surgery, Division of Surgery, Houston, TX, USA; 2Department of Oncology, Royal North Shore Hospital, St Leonards, Australia; 3Melanoma Institute Australia, The University of Sydney, Sydney, Australia; 4Mater Hospital, Sydney, Australia; 5Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Hannover, Germany; 6Department of Dermatology, University Medical Center Mainz, Mainz, Germany; 7Medical Affairs Oncology and Long Term Care, Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA; 8Department of Dermatology, St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Australia; 9The University of Melbourne, Parkville, Victoria, Australia;10Skin Health Institute Inc, Carlton, Victoria, Australia

Background: Sonidegib, a Hedgehog pathway inhibitor, is approved to treat patients with locally advanced basal cell carcinoma (BCC) not amenable to curative surgery or radiotherapy. Here, we present hematology laboratory shifts in patients with advanced BCC receiving sonidegib 200mg once daily (QD).

Methods: BOLT was a randomized, double-blind, multicenter, Phase 2 study with patients randomized 1:2 to receive sonidegib 200 or 800mg orally QD, respectively. Hematology assessments were performed bi-weekly for 14 weeks, then every four weeks until Week 77, then followed as clinically indicated until end of treatment. Hematology evaluations were performed by a central laboratory. Safety assessments included adverse event monitoring.

Results: Through 42 months of treatment with sonidegib 200mg (n=70), 24.1 percent and 7.6 percent of patients had Grade 1 or 2 anemia vs 3.8 percent and 0 percent of patients had Grade 1 or 2 hyperhemoglobinemia. Zero patients had a Grade 3 or 4 hemoglobin shift. Overall, 16.5 percent, 8.9 percent, and 2.5 percent of patients had Grade 1, 2, or 3 lymphocytopenia; 0 percent had Grade 4 shift. Grade 1 or 2 neutropenia was detected in 6.3 percent and 1.3 percent of patients, respectively; 0 percent had Grade 3 or 4. Overall, 6.3 percent and 1.3 percent of patients had grade 1 or 4 thrombocytopenia, respectively, while zero patients had Grade 2/3. Grade 1 or 2 leukopenia was observed in 5.1 percent and 1.3 percent of patients, respectively; 0 percent had grade 3/4 shifts.

Conclusion: Through 42 months of treatment with sonidegib 200mg QD, most patients experienced no hematology changes or Grade 1 hematology shifts.

Disclosures: MM has participated on advisory boards and received honoraria from Genentech; Novartis Pharmaceuticals Corporation; Sun Pharma; and Regeneron Pharmaceuticals. 

AG has participated on advisory boards for Bristol-Myers Squibb, Pfizer, and Sanofi; received honoraria from Novartis; and received travel support from Astellas and Bristol-Myers Squibb. 

RG serves as consultant to Almirall; Amgen; Bristol-Myers Squibb; Merck Serono; Merck Sharp & Dohme; Novartis; Pfizer; Pierre-Fabre; Roche; Sanofi Genzyme; Sun Pharma; and 4SC; has received travel grants and honoraria for lectures from Almirall; Amgen; Bristol-Myers Squibb; Merck Serono; Merck Sharp & Dohme; Novartis; Pierre-Fabre; Roche; and Sun Pharma; and received research funding from Amgen, Johnson & Johnson, Merck-Serono, and Novartis. 

CL acted as a speaker for, participated in an advisory board for, and received honoraria from Bristol-Myers Squibb, Roche, Novartis, and Merck Sharp & Dohme. 

NS is an employee of Sun Pharmaceutical Industries, Inc. 

PF has participated in clinical trials (investigator), been on an advisory board, been a consultant, received speaker’s bureau/honoraria, and/or received research and/or travel grants from the following: AbbVie; Akaal; Amgen; Arcutis; Aslan; Astra Zeneca; Bristol-Myers Squibb; Boehringer Ingelheim; Botanix; Celgene; Celtaxsys; CSL; Cutanea; Dermira; Eli Lilly and Company; Galderma; Geneseq; Genetech; GSK; Hexima; Janssen; Leo Pharma; Mayne Pharma; MedImmune; Merck; Novartis; Pfizer; Regeneron Pharmaceuticals Inc.; Reistone; Roche; Sanofi; Sun Pharma; UCB Pharma; and Valeant.

Funding: This study was funded by Sun Pharma.

 

Improving patient selection for adjuvant therapy: Considerations for the role of the 31-gene expression profile

Presenters: Ahmed K,1 Bailey CN,1 Martin B,1 Kurley SJ,1 Goldberg MS,1,2 Petkov VI,3, Covington KR1

Affiliations: 1Castle Biosciences, Inc. Friendswood, TX; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3National Cancer Institute, Surveillance Research Program, Bethesda, MD

Background: Cutaneous melanoma guidelines suggest patients with Stage I-IIA are low risk and Stage IIB-III high risk for recurrence and death. Pembrolizumab was approved in late 2021 for stage IIB-IIC disease; however, a minimal survival difference at 12 months relative to placebo and an associated high adverse event (AE) rate (7% RFS benefit vs. 12% higher adverse events) suggests refinement in patient selection for therapy is needed. Identifying stage IIB-IIC patients who have high survival rates without adjuvant therapy can improve the benefit-risk ratio of adjuvant therapy.

Methods: The 31-gene expression profile (31-GEP) test stratifies patients into low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) risk of recurrence, metastasis, and death. Patient data provided through collaboration with the National Cancer Institute’s Surveillance, Epidemiology, and End Results program (diagnosis 2016-2018) was linked to data for patients tested with the 31-GEP (Stage I-III: n=4,687). Kaplan-Meier analysis with log-rank test was used to analyze melanoma-specific survival (MSS).

Results: In patients with Stage I-IIA (n=4,038), those with a Class 1A result had higher 3-year MSS than those with a Class 1B/2A or Class 2B result (99.8% vs. 97.5% vs. 94.8%, p<0.001). Similar results were seen for patients with Stage IIB-IIC (n=376; Class 1A: 100% vs. Class 1B/2A: 100% vs. Class 2B: 88.3%, p=0.04) and Stage III (n=273; Class 1A: 96.1% vs. Class 1B/2A: 90.9% vs. Class 2B: 79.6%, p=0.03).

Conclusion: Using the 31-GEP test to improve risk-stratification with traditional staging allows physicians and patients to make risk-aligned management decisions, particularly by identifying low-risk patients with good survival profiles who may consider avoidance of the AE risks from therapy, and high-risk patients with higher likelihood of developing metastasis who may consider additional intervention.

 

Incorporating the 40 gene expression profile (40-GEP) test for poorly differentiated cutaneous squamous cell carcinoma (cSCC) tumors mitigates risk assessment uncertainty from histologic grading

Presenters: Farberg AS,1 Siegel JJ,2 Kurley SJ,2 Fitzgerald AL,2 Prasai A,2 Goldberg MS,2 Ibrahim S,3 Estrada SI4

Affiliations: 1Baylor Scott & White Health System; 2Castle Biosciences Inc.; 3University of Rochester; 4Dermatology and Affiliated Laboratories

Background: Poor histological differentiation is a well-documented risk factor for metastasis in cutaneous squamous cell carcinoma (cSCC) and a high-risk factor for Brigham and Women’s Hospital T-stage (BWH). However, as previously reported (Prezzano et al. 2021), differentiation is an imperfect risk indicator due to subjectivity in distinguishing between moderate and poor classifications. As part of developing objective prognostic biomarkers, the 40-GEP test was independently validated to accurately classify risk for regional or distant metastasis into three categories: low (Class 1), moderate (Class 2A), or high risk (Class 2B). 

Objective: The goal of this study was to investigate if the 40-GEP stratifies risk among a potentially histologically uncertain cohort to support risk-aligned treatment decisions.

Methods: From a previously published cohort (Ibrahim et al. 2021) (n=420), a subset of cases was identified whose BWH T-stage would change if the tumor differentiation status of ‘moderate’ or ‘poor’ was downgraded or upgraded, respectively. These cases were imputed to the opposite result and then re-staged (n=171). Kaplan Meier survival analysis was performed.

Results: Potential uncertainty in histological differentiation resulted in 132 and 39 patients up- and down-staged respectively. Within this subset of patients, the overall 3-year metastasis free survival was 81.9 percent. Importantly, the 40-GEP was able to significantly stratify risk (p=0.02; 90.1% Class 1, 78.6% Class 2A, 62.5% Class 2B).

Conclusion: The 40-GEP can aid staging and risk assessment in situations in which the distinction between poor and moderate histological grading is challenging, thus adding clarity and confidence to risk-aligned treatment decisions for the benefit of patients.

 

The efficacy and safety of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light for the treatment of facial cutaneous squamous cell carcinoma in situ

Presenters: Nestor MS,1–3 Han H,1 Yousefian F,1 Smythe C1

Affiliations: 1Center for Clinical and Cosmetic Research, Aventura, FL; 2Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; 3Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL

Background: Aminolevulinic acid 20% solution photodynamic therapy (ALA-PDT) is approved for the treatment of actinic keratoses on the face, scalp, and upper extremities. ALA-PDT is also a potential treatment option for squamous cell carcinoma (SCC), the second-most common cutaneous malignancy. This study evaluated the safety and efficacy of ALA-PDT in combination with pulsed dye laser (PDL) for the treatment of facial cutaneous SCC in situ (isSCC).

Methods: Patients with biopsy-confirmed isSCC on the face were recruited for this single-center, investigator-initiated, open-label pilot clinical trial. Only lesions with a diameter of 0.4 to 1.3cm were considered. ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18 to 24 hours, followed by PDL treatment and then blue light illumination (ALA-PDL-PDT). A second ALA-PDL-PDT session was performed 30 days later. The lesion was surgically excised for histological assessment 4 to 6 weeks following the second treatment. The primary efficacy endpoint was the proportion of patients achieving histological clearance of isSCC at end of treatment. The secondary efficacy endpoint was the proportion of patients with clinical clearance of the skin lesion. Safety was assessed from adverse events (AEs) and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration). Lesion site pain was measured using a visual analog scale ranging from 0 (no pain) to 10 (worst pain possible) within 15 minutes of each treatment session.

Results: Of the 20 patients enrolled, 17 (85%) achieved histological clearance at end of treatment. After excluding two patients with residual isSCC exhibiting skip lesions, the histological clearance rate was 17/18 patients (94%). The frequency of LSRs peaked within one week following each treatment session and steadily decreased afterward. The major contributors to LSRs were erythema and scaling. The majority of treated patients (65%) did not experience any AEs. Reported AEs included allergic contact dermatitis, blurry vision, right ear pain, right leg cellulitis, double vision, hypotension, and wound site infection. None of the reported AEs were serious or considered related to study treatment. The mean ± standard deviation posttreatment pain score was 2.95 ± 2.97.

Conclusion: ALA-PDL-PDT is a well-tolerated, safe, and highly efficacious treatment option for small isSCC on the face.

Funding: Funding for this study was provided by Sun Pharma.


HIDRADENITIS SUPPURATIVA


Secukinumab in moderate-to-severe hidradenitis suppurativa: Primary endpoint analysis from the SUNSHINE and SUNRISE Phase 3 trials

Presenters: Kimball AB,1 Alavi, A,2 Jemec GBE,3 Gottlieb A,4 Wei X,5 Wozniak MB,6 Uhlmann L,7 Martinez AL,7 Keefe D,8 Martin R,8 Chen L,8 Muscianisi E8

Affiliations: 1Department of Dermatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Department of Dermatology, Mayo Clinic, Rochester, MN, USA; 3Department of Dermatology, Zeeland University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark; 4Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Novartis Pharma Shanghai, China; 6Novartis Ireland Limited, Dublin, Ireland; 7Novartis Pharma AG, Basel, Switzerland; 8Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Background: Hidradenitis suppurativa (HS) is a chronic skin disease characterised by inflammatory nodules, abscesses and draining tunnels, with limited effective treatment options. HS is characterized by high patient burden and a recognized need for novel therapeutic options. Secukinumab is a fully human, monoclonal antibody which selectively neutralises interleukin-17A (IL-17A). Here, the primary endpoint analysis (Week 16) results from SUNSHINE (NCT03713619) and SUNRISE (NCT03713632), two double-blind, identical, Phase 3 randomized controlled trials of secukinumab in patients with moderate-to-severe HS, are described.

Methods: In both trials, adult patients with moderate-to-severe HS were randomized to receive subcutaneous secukinumab 300mg every two (SECQ2W) or four weeks (SECQ4W), or placebo. The primary objective of both trials was to demonstrate superiority of secukinumab over placebo in achieving hidradenitis suppurativa clinical response (HiSCR) at Week 16. Key secondary endpoints at Week 16 included percentage change from baseline in abscess and inflammatory nodule (AN) count, proportion of patients experiencing a flare, and proportion of patients with NRS30 (skin pain) response (reported as pooled data from both trials).

Results: 1,084 patients were randomized in SUNSHINE (n=541, SECQ2W [n=181]; SECQ4W [n=180]; placebo [n=180]) and SUNRISE (n=543, SECQ2W [n=180]; SECQ4W [n=180]; placebo [n=183]), with 93.6 percent (1,015/1,084) of patients completing 16 weeks of treatment (56.3% female, mean age 36.2). The SECQ2W dose regimen met the primary endpoint (HiSCR at Week 16) in both studies (SUNSHINE: SECQ2W [45.0%] vs placebo [33.7%]; SUNRISE: SECQ2W [42.3%] vs placebo [31.2%]). SECQ2W met all secondary endpoints in both trials except the proportion of patients experiencing a flare (met only in SUNSHINE); a significantly greater decrease in AN count (SUNSHINE: SECQ2W [-46.8%] vs placebo [-24.3%]; SUNRISE: SECQ2W [-39.3%] vs placebo [-22.4%]) and significantly higher NRS30 response (SECQ2W [38.9%] vs placebo [26.9%]) compared with placebo at Week 16. Significantly fewer patients in the SECQ2W dosing regimen experienced flares over 16 weeks versus placebo in SUNSHINE (15.4% vs 29.0%), with numerically fewer flares observed versus placebo in SUNRISE (20.1% vs 27.0%). The SECQ4W dose regimen met primary and all secondary endpoints (excluding pain) in SUNRISE only; HiSCR (SECQ4W [46.1%] vs placebo [31.2%]), AN count (SECQ4W [-45.5%] vs placebo [-22.4%]) and disease flares (SECQ4W [15.6%] vs placebo [27.0%]). Secukinumab was well-tolerated with no new safety signals.

Conclusion: Secukinumab is effective in treating moderate-to-severe HS with a favourable safety profile. IL-17A inhibition thus appears an efficacious therapeutic option in this population.

Disclosures: ABK is a consultant and investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, and UCB; investigator for Incyte and AnaptysBio; consultant for Bayer, Boehringer Ingelheim, Ventyx, Moonlake, Lilly, Concert, EvoImmune, Sonoma Bio, Sanofi, receives fellowship funding from Janssen; and serves on the Board of Directors for Almirall. 

AA has received honoraria as a consultant or advisory board participant from AbbVie, Janssen, Novartis, Boehringer-Ingelheim, InflaRx, and UCB and is an investigator for Processa and Boehringer-Ingelheim. 

GBEJ has served as a consultant for AbbVie, Coloplast, Leo Pharma, Novartis, UCB, and InflaRX; as an investigator for AbbVie, Leo Pharma, Novartis, Regeneron, UCB, and InflaRX; has received unrestricted grants from AbbVie, Leo Pharma, and Novartis; has served on Adboards for AbbVie, Janssen-Pharma, MSD, and Novartis; and as a speaker for AbbVie, Coloplast, Leo Pharma, and Galderma. 

AG has received honoraria as an advisory board member, non-promotional speaker or consultant for: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharmaceutical Industries, UCB, and Xbiotech (stock options for an RA project). 

AG has also received research/educational grants from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharmaceutical Industries, Bristol-Myers Squibb and UCB; all funds go to Icahn School of Medicine at Mount Sinai. 

XW is an employee at Novartis Pharma Shanghai, China. 

MBW is an employee and stockholder at Novartis Ireland Limited, Dublin. 

LU, and ALM are employees and stockholders at Novartis Pharma AG, Basel, Switzerland. 

DK, RM, LC, and EM are employees and stockholders at Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.


MISCELLANEOUS


Dupilumab efficacy in patients with chronic spontaneous urticaria by IgE level: LIBERTY-CSU CUPID Study A

Presenters: Maurer M,1,2 Casale TB,3 Saini SS,4 Ben-Shoshan M,5 Radin A,6 Akinlade B,6 Laws E,7 Mannent LP8

Affiliations: 1Institute of Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 2Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany; 3University of South Florida, Tampa, FL, USA; 4Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA; 5McGill University Health Centre, Montreal, QC, Canada; 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 7Sanofi, Bridgewater, NJ, USA; 8Sanofi, Chilly-Mazarin, France

Background: Chronic spontaneous urticaria (CSU) causes recurrent itchy hives and/or angioedema, significantly impacting quality of life. Many patients experience a substantial disease burden despite treatment with licensed and escalated doses of H1 antihistamines.

Methods: In LIBERTY-CSU CUPID Study A (NCT04180488), a randomized, placebo-controlled, 24-week, Phase 3 trial, patients (≥6 years) with CSU who remained symptomatic despite H1 antihistamine treatment received add-on dupilumab (n=70) (adults/adolescents ≥60kg: 300mg; adolescents <60kg/children ≥30kg: 200 mg) or matching placebo (n=68) subcutaneously every two weeks. Endpoints included change from baseline at Week-24 over seven days in Itch Severity Score (ISS7), Hives Severity Score (HSS7), and Urticaria Activity Score (UAS7).

Results: Baseline characteristics were balanced; mean ISS7 and UAS7 (dupilumab/placebo) were 16.1/15.7 and 31.9/30.8, respectively. At Week-24, least squares (LS) mean change from baseline in ISS7 (range: 0–21) was –10.2/–6.0 (dupilumab/placebo, respectively) (LS mean difference –4.2; P=0.0005) and for UAS7 (range: 0–42) was –20.5/–12.0 (difference –8.5; P=0.0003). Baseline median serum total IgE was 101.0IU/mL (overall population). Dupilumab significantly reduced itch (ISS7), hives (HSS7), and urticaria activity (UAS7) at Week-24 regardless of baseline serum total IgE (<100 /≥100IU/mL): ISS7 LS mean difference vs. placebo (95% confidence interval)−4.2(−7.86, −0.62)/−4.6(−8.22, −1.04), respectively; HSS7, −4.2(−7.60, −0.70)/−6.1(−9.95, −2.33); UAS7, –8.2(–15.04, –1.29)/–10.6(–17.72, –3.54). Occurrence of treatment-emergent adverse events (TEAEs) for dupilumab/placebo were 35(50.0%)/40(58.8%); injection-site reactions, 8(11.4%)/9(13.2%); conjunctivitis, 0/1(1.5%); serious TEAEs, 2(2.9%)/5(7.4%).

Conclusion: Dupilumab demonstrated clinically meaningful and statistically significant improvements in patients with H1 antihistamine-resistant CSU regardless of baseline IgE level and was well tolerated.

Funding: Funding was provided by Sanofi and Regeneron Pharmaceuticals, Inc.

 

Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: Pooled results from two Phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Presenters: Yosipovitch G,1 Kwatra SG,2 Mollanazar N,3 Ständer S,4 Satoh T,5 Laws E,6 Mannent LP,7 Mortensen E,8 Maloney J,8 Shi G,6 Bansal A,8 Martinčová R9

Affiliations: 1University of Miami, Miami, FL, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3University of Pennsylvania, Philadelphia, PA, USA; 4University Hospital Münster, Münster, Germany; 5National Defense Medical College, Tokorozawa, Japan; 6Sanofi, Bridgewater, NJ, USA; 7Sanofi, Chilly-Mazarin, France; 8Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 9Sanofi, Prague, Czech Republic

Background: Prurigo nodularis (PN) is a chronic inflammatory and pruritic skin condition which substantially affects quality of life. Two randomized clinical trials, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), demonstrated the efficacy and safety of dupilumab in adults with PN.

Methods: PRIME and PRIME2 were multicenter, randomized, placebo-controlled, double-blinded, Phase 3 trials, during which patients received dupilumab 300mg (loading dose, 600mg) or placebo every two weeks for 24 weeks. Itch severity was measured by Worst Itch Numerical Rating Scale (WI-NRS; 0–10). Severity of skin lesions was assessed using Investigator’s Global Assessment for PN-Stage (IGAPN-S; 0–4). Efficacy endpoints were proportion of patients: with WI-NRS reduction of 4 or more points, who achieved IGA PN-S 0 or 1, and who achieved concomitantly WI-NRS reduction of 4 or more points and IGA PN-S 0 or 1, at Week 12 and at Week 24.

Results: At baseline, demographic and disease characteristics were balanced between the PRIME and PRIME2 pooled dupilumab (n=153), and pooled placebo groups (n=158); and the overall mean (standard deviation) WI-NRS was 8.5 (1.0); 66.3 percent of patients had 20–99 nodules, and 33.7 percent had over 100 nodules. At Week 12, the ≥4-point reduction in WI-NRS in the dupilumab group was achieved by 62 patients (40.5%), and at Week 24, by 90 (58.8%), vs. 30 (19.0%) in the placebo group at each time point (P<0.0001 for both). IGA PN-S 0 or 1 was achieved by 44 (28.8%) dupilumab-treated patients vs. 19 (12.0%) in the placebo group at Week 12 (P=0.0002), and respectively by 71 (46.4%) vs. 27 (17.1%) at Week 24 (P<0.0001). The concomitant reduction in WI-NRS by 4 or more points and IGA PN-S 0 or 1 was achieved by 28 (18.3%) dupilumab-treated patients vs. 11 (7.0%) in the placebo group at Week 12 (P=0.0021), and respectively by 54 (35.3%) vs 14 (8.9%) at Week 24 (P<0.0001). The most common adverse events were headache (5.3% vs 5.7%), neurodermatitis (2.0% vs 5.7%), skin infections (3.9% vs 7.6%), and injection-site reactions (3.9% vs 5.7%) in dupilumab vs placebo groups.

Conclusion: Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions vs placebo in patients with PN, confirming the findings from individual PRIME and PRIME2 studies. The safety profile of dupilumab was consistent with the known safety profile in its approved indications.

 

Efgartigimod: clinical development of a novel neonatal Fc receptor antagonist in the treatment of autoimmune diseases

Presenters: Ostrovskaya O,1 Sips M,1 Ulrichts P,1 Trainor L,1 Verheesen P,1 Stoykov I1

Affiliations: 1Argenx, Ghent, Belgium

Background: Immunoglobulin G (IgG) autoantibodies play a key role in the pathogenesis of various autoimmune diseases. The neonatal Fc receptor (FcRn) is the central regulator of IgG homeostasis, rescuing IgG (including pathogenic autoantibodies) and albumin from lysosomal degradation, and is responsible for their long half-life. Efgartigimod, an FcRn antagonist, is a human IgG1-derived Fc fragment that outcompetes endogenous IgG binding, reduces IgG recycling, and increases IgG degradation. Efgartigimod is approved in the US and Japan for treatment of generalized myasthenia gravis in adult

Methods: Studies in both healthy volunteers and participants with IgG-mediated autoimmune diseases have been completed. Ongoing studies include Phase 3 studies in immune thrombocytopenia (ADVANCE SC) and pemphigus vulgaris and foliaceus (ADDRESS), and Phase 2/3 studies in chronic inflammatory demyelinating polyneuropathy (ADHERE), bullous pemphigoid (BALLAD), and myositis (ALKIVIA).

Results: Across all studies to date, efgartigimod reduced total IgG, including pathogenic IgG, which corresponded with clinical improvements in each respective population. In an open-label, Phase 2 study in participants with mild-to-moderate pemphigus vulgaris or foliaceus, disease control was achieved in 90 percent of participants (median time: 17 days) while complete clinical remission was achieved in 64 percent of participants (median time: 92 days) in the last two cohorts. IgG levels including autoreactive anti-desmoglein (Dsg)-1/3 autoantibodies were reduced by more than 60 percent following treatment. Intriguingly, in several participants responding to efgartigimod, loss of Dsg-specific B cells was observed

Conclusion: In all studies to date, efgartigimod was well tolerated and adverse events were mainly mild-to-moderate. FcRn inhibition by efgartigimod is a promising potential therapeutic option for several autoimmune diseases mediated by pathogenic IgG autoantibodies.

 

Evaluation of a novel inorganic tinted sunscreen enriched with five antioxidants for protection against UVA1 and VL induced hyperpigmentation and erythema

Presenters: Yousefian O,1 Aeschliman L,1 Mortillo S,1 and Ruvolo E1

Affiliations: 1Beiersdorf Inc., Florham Park, NJ

Background: Visible light (VL, 400-700 nm) and long wavelength UVA1 (VL+UVA1, 370-700 nm) have been reported to cause erythema in light skin phototypes, Fitzpatrick Skin Types I-III (FST I-III), and to exacerbate pigmentary dermatologic conditions (e.g., melasma, hyperpigmentation, post-inflammatory hyperpigmentation) in individuals with dark skin phototypes (FST IV-VI). Until recently, there remained limited options for photoprotection against VL+UVA1, including tinted (containing iron oxide [Fe2O3] or pigmentary titanium dioxide [TiO2]) organic-based (chemical) filters-based or the utilization of a five antioxidant (5 AOX) enriched formulation. Zinc oxide (ZnO) and TiO2 are often utilized in the development of mineral-based (inorganic) sunscreens as the active ingredients to protect against broad-spectrum ultraviolet (UV) radiation via their absorption properties. However, some of these products often leave a white cast, particularly on dark skin, making these products unfavorable, altering skin tone appearance, leading to concerns for sunscreen compliance. The addition of tint (Fe2O3) to mineral-based sunscreens aims to improve the cosmetic elegance, blendability into multiple skin tones, and overall compliance for daily sunscreen use.

Objective: This study aims to evaluate the photoprotection properties of a novel Zn-based inorganic tinted sunscreen enriched with five antioxidants (5 AOX) against VL+UVA1 induced biologic effects (hyperpigmentation and erythema).

Methods: Ten healthy adult subjects with FST IV-VI were enrolled and the effectiveness of the new Zn/Fe2O3/5 AOX sunscreen, compared to several commercially available tinted and non-tinted mineral sunscreens was evaluated. The erythema and pigmentation assessment was performed by diffused reflectance spectroscopy (DRS), polarized photography, and investigator global scoring immediately, 24 hours, and seven days after irradiation (320 J/cm2).

Results: DRS results demonstrated that the novel Zn/Fe2O3/5 AOX can effectively reduce immediate erythema and pigmentation as well as delay pigmentation when compared with formulas containing ZnO only (p≤0.05). Not all inorganic/Fe2O3 formulas could significantly reduce erythema and pigmentation induced by UVA1/VL when compared with ZnO-only formula.

Conclusion: These results highlight the enhanced effects of 5 AOX-enriched tinted mineral sunscreen to be photoprotective against VL+UVA1, with a blendable tint designed for use on skin of all color, aimed at improving patient compliance and overall sunscreen use.

 

Evaluation of an SPF50 sunscreen containing photolyase and antioxidants for its anti-photoaging properties

Presenters: Kern, JA,1 Wood E,2 Almukhtar R,3 Angra K,4 Lipp M,5 Goldman MP4

Affiliations: 1University of California San Diego School of Medicine, San Diego, California; 2Westlake Dermatology, Austin, Texas; 3Henry Ford Health System, Department of Dermatology, Detroit, Michigan; 4Cosmetic Laser Dermatology, A West Dermatology Company, San Diego, California; 5Skin Aesthetica, Redlands, California;

Background: Skin exposure to ultraviolet radiation (UVR) causes DNA damage, which can leadto mutagenesis, carcinogenesis, cellular death, and photoaging. Signs of photoaging include wrinkling, erythema, skin laxity, uneven skin texture, and hyperpigmentation. Photolyase is an exogenous DNA repair enzyme that can restore DNA integrity when applied topically to human skin. Antioxidants also play a key role in reducing UVR-associated molecular damage.

Objective: To assess the efficacy of a mineral-based sunscreen containing 10.7% zinc oxide (SPF50) with the active ingredients photolyase, antioxidants (Vitamin E and Peptide Q10), and peptides in both protecting against and repairing visible signs of photoaging.

Methods: In an open-label, single-center, 12-week study, patients aged 35–65 years and Fitzpatrick Skin Types II–IV applied the sunscreen daily for 84 days. VISIA photography was performed at baseline as well as 6- and 12-week follow-ups. At each visit, the investigator and subject evaluated clinical photoaging parameters including overall photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone evenness, tactile roughness, and radiance.

Results: The Investigator Global Aesthetic Improvement Scale (IGAIS) found that 63 percent of patients showed improvement at Week 6 and 81 percent at Week 12. The Subject Global Aesthetic Improvement Scale (SGAIS) showed 58% percent and 62.5 percent of patients reported the appearance of their skin was improved at Week 6 and 12, respectively. Overall, there was a statistically significant improvement in skin radiance as well as improvement in overall facial aesthetics reported by both investigators and subjects.

Conclusion: A mineral-based SPF50 sunscreen containing photolyase, antioxidants, and peptides is effective at repairing some clinical signs of photoaging.

 

Long-term safety and tolerability of remibrutinib (LOU064) in Phase 2b study in chronic spontaneous urticaria patients

Presenters: Giménez-Arnau A,1 Marcus Maurer M,2,3 Metz M,2,3 Jain V,4 Walsh P,5 Lheritier K,6 Hugot S,6 Zouater H,6 Haemmerle S,6 Zharkov A6

Affiliations: 1Department of Dermatology, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain; 2Urticaria Center of Reference and Excellence (UCARE), Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 3Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany; 4Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Canada; 5Novartis Ireland Limited, Dublin, Ireland; 6Novartis Pharma AG, Basel, Switzerland.

Background: Remibrutinib (LOU064), a novel, highly selective and potent oral covalent Bruton’s tyrosine kinase inhibitor, is in Phase 3 clinical development for the treatment of chronic spontaneous urticaria (CSU).

Objective: We report the safety and tolerability of remibrutinib for up to 52 weeks in patients with CSU from a final analysis of the dose-finding Phase 2b trial and an interim analysis of its extension study (ES).

Methods: In the randomized, double-blind, placebo-controlled Phase 2b core study (CS), adult patients with CSU received remibrutinib 10mg once daily (qd), 35mg qd, 100mg qd, 10mg twice daily (bid), 25mg bid, 100mg bid or placebo (1:1:1:1:1:1:1) for up to 12 weeks (NCT03926611). At end of the CS, eligible patients received remibrutinib 100mg bid for up to 52 weeks in an ongoing open-label ES (NCT04109313). Adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs), vital signs and laboratory parameters were assessed.

Results: In the randomized, double-blind, placebo-controlled Phase 2b core study (CS), adult patients with CSU received remibrutinib 10mg once daily (qd), 35mg qd, 100mg qd, 10mg twice daily (bid), 25mg bid, 100mg bid or placebo (1:1:1:1:1:1:1) for up to 12 weeks (NCT03926611). At end of the CS, eligible patients received remibrutinib 100mg bid for up to 52 weeks in an ongoing open-label ES (NCT04109313). Adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs), vital signs and laboratory parameters were assessed.

Conclusion: Remibrutinib showed a favorable safety profile across the dose range, with no new safety signals during exposure to a 100mg bid dose up to 52 weeks in patients with CSU.

Funding: Funding was provided by Novartis Pharma AG.

Disclosures: Ana Giménez-Arnau reports roles as a medical advisor for Uriach Pharma, Sanofi and Genentech, Novartis, FAES, GlaxoSmithKline, Amgen, Thermo Fisher and has research grants supported by Uriach Pharma, Novartis and Instituto Carlos III- FEDER; she also participates in educational activities for Uriach Pharma, Novartis, Genentech, Menarini, Leo Pharma, GlaxoSmithKline, MSD, Almirall, Avene and Sanofi. Marcus Maurer is or recently was a speaker and/or advisor for and/or has received research funding from Amgen, Allakos, Aralez, AstraZeneca, Celldex, FAES, Genentech, GI Innovation, Kyowa Kirin, Leo Pharma, Menarini, Novartis, Moxie, MSD, Roche, Sanofi, Third Harmonic, UCB, and Uriach. Martin Metz reports personal fees from Amgen, Aralez, Argenx, AstraZeneca, Celldex, Moxie, Novartis, Roche, Sanofi and Uriach. Vipul Jain has consulted as/or advised and/or received research funding from Pediapharm, Medexus, Sanofi, Regeneron, Bausch, Novartis, AbbVie, Aralez, ALK, Celgene, Amgen, Leo Pharma, Mylan, Pfizer, Covis Pharma, Galderma, Eli Lilly, and AstraZeneca. Pauline Walsh is an employee of Novartis Ireland Limited, Dublin, Ireland. Karine Lheritier, Sophie Hugot, Hichem Zouater, Sibylle Haemmerle and Artem Zharkov are employees of Novartis Pharma AG, Basel, Switzerland.

 

Onychomycosis dermatophytoma treatment: A systematic review of the literature

Presenters: Lipner SR,1 Vlahovic TC,2 Elewski B,3 Ghannoum M,4 Joseph WS5

Affiliations: 1Department of Dermatology, Weill Cornell Medicine, New York, NY; 2Temple University School of Podiatric Medicine, Philadelphia, PA; 3University of Alabama at Birmingham School of Medicine, Birmingham, AL; 4Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH; 5Arizona College of Podiatric Medicine, Midwestern University, Glendale, AZ

Background: Dermatophytomas/longitudinal spikes are a poorly understood form of onychomycosis presenting as dense yellow/white streaks/patches in the subungual space with fungal masses encased in biofilm. Historically, dermatophytomas have been considered hard-to-treat, and treatment response data are limited as these patients are frequently excluded from onychomycosis clinical trials. Newer topical antifungals, however, can penetrate the nail plate and spread in the subungual space, which may make them effective in the treatment of onychomycosis complicated by dermatophytoma. 

Objective: The objective of this systematic review was to assess efficacy of oral/topical drugs for dermatophytoma treatment.

Methods: Pubmed and Embase were searched for keywords “dermatophytoma” or “longitudinal spike” in December 2021. Included studies comprised English-language publications, with ≥5 participants with dermatophytoma, and use of an oral or topical drug (US-approved for onychomycosis) without surgical removal.

Results: Of 44 unique publications, six were included (4 post-hoc/retrospective, two open label): three topical efinaconazole 10% (N=106 with dermatophytoma; two studies: 48-72 weeks treatment; one study: approximately 64 weeks mean treatment), one topical tavaborole 5% (N=39; 24-52 weeks), and two oral terbinafine 125mg or 250mg (N=23; 12 weeks treatment, follow-up at Weeks 24 or 48). Efficacy outcome definitions, when provided, varied across studies. In studies where outcomes were defined using both clinical and mycological results (ie, more stringent definitions), cure rates were 41.5 percent and 63 percent for topical efinaconazole 10% and 42 percent for oral terbinafine. When outcomes were defined using clinical results or not defined at all, topical efinaconazole 10% showed higher rates in three studies (60%-100%) versus one study each of oral terbinafine (45%) and topical tavaborole 5% (28.2%). In studies where outcomes were defined via mycological results, two studies of efinaconazole demonstrated higher rates of negative KOH and/or negative culture (72.0%-100%) than a study of oral terbinafine (67%).

Conclusion: In this systematic review of dermatophytoma/longitudinal spike treatments, topical efinaconazole generally led to higher rates of improvement/cure than topical tavaborole or oral terbinafine, though endpoints differed across studies and there were no head-to-head comparisons. While dermatophytomas have historically been considered a poor prognostic factor, results demonstrate successful treatment is possible, particularly with effective topical treatments such as efinaconazole 10%.

Funding: Ortho Dermatologics provided funding for this study


PSORIASIS


Bimekizumab efficacy through one year in patients with moderate-to-severe plaque psoriasis in subgroups defined by prior biologic treatment: Pooled results from four Phase 3/3b trials

Presenters: Lebwohl M,1 Armstrong A,2 Merola JF,3 Gottlieb AB,1 Davis L,4 Gomez B,5 Wiegratz S,6 Cross N,4 Strober B7,8

Affiliations: 1Dept. of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Keck School of Medicine of USC, Dermatology, Los Angeles, CA, USA; 3Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 4UCB Pharma, Morrisville, NC, USA; 5UCB Pharma, Smyrna, GA, USA; 6UCB Pharma, Monheim, Germany; 7Yale University, New Haven, CT, USA; 8Central Connecticut Dermatology Research, Cromwell, CT, USA

Background: Prior biologic treatment can impact responses to future biologics in patients with plaque psoriasis.1 We assess clinical and health-related quality of life (HRQoL) outcomes in bimekizumab (BKZ)-treated patients without prior biologic treatment (biologic-naïve) vs those with prior biologic treatment (biologic-experienced).

Methods: Data were pooled from the BE SURE (NCT03412747), BE VIVID (NCT03370133), BE READY (NCT03410992), and BE RADIANT (NCT03536884) Phase 3/3b trials. Included patients received BKZ 320mg every four weeks (wks; Q4W) during Wks 0–16, then BKZ 320mg Q4W or Q8W as maintenance dosing for the remainder of the double-blinded trials. In this analysis, BKZ 320mg Q4W and Q8W treatment groups were combined (BKZ Total). Patients with previous primary failure (no response within 12 wks) to either 1 or more anti-IL-17 or more than one other biologic treatments were excluded from all trials. We assessed Psoriasis Area and Severity Index (PASI)90 at Wk48 and Dermatology Life Quality Index (DLQI)0/1 responses at Wk48/52 (DLQI measured on a different schedule in BE VIVID) in patients who had received 0, 1, 2 or ≥3 prior biologics, respectively. Responses by type of prior biologic were also reported. Missing data were imputed using non-responder imputation.

Results: 1,186 patients randomized to BKZ continued to the maintenance periods of the trials and received BKZ Total; 745 were biologic-naïve, whilst 314, 98, and 29 were biologic-experienced and received 1, 2, or ≥3 prior biologics, respectively. Wk48 PASI90 responses were: biologic-naïve: 86.6 percent; one prior biologic: 88.2 percent; two prior biologics: 84.7 percent; three or more prior biologics: 69.0 percent. Wk48/52 DLQI0/1 responses were: biologic-naïve: 77.6 percent; one prior biologic: 80.3 percent; two prior biologics: 82.7 percent; three or more prior biologics: 65.5 percent. In biologic-experienced patients (anti-IL-17: n=236; anti-TNF: n=179; anti-IL-12/23: n=66; anti-IL-23: n=64), Wk48 PASI90 responses by prior biologic were: anti-IL-17: 86.9 percent; anti-TNF: 84.9 percent; anti-IL-12/23: 81.8 percent; anti-IL-23: 84.4 percent. Wk48/52 DLQI0/1 responses were: anti-IL-17: 78.8 percent; anti-TNF: 80.4 percent; anti-IL-12/23: 78.8 percent; anti-IL-23: 75.0 percent.

Conclusion: High levels of skin clearance, in addition to HRQoL benefit, were observed with BKZ in both biologic-naïve and biologic-experienced patients. Responses were slightly lower in those who received 3 or more prior biologics; these data should be interpreted with caution due to the small number of patients in this subgroup. PASI90 and DLQI0/1 responses were generally consistent, regardless of the type of prior biologic used.

Funding: UCB Pharma provided funding for this study.

Disclosures: ML: Employee of Mount Sinai and receives research funds from: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB Pharma; consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica.

AA: Research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, EPI, Incyte, Janssen, LEO Pharma, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sun Pharma, Sanofi, and UCB Pharma.

JFM: Consultant and/or investigator for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma.

ABG: Honoraria as an advisory board member and consultant for: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech (stock options for an RA project); research/educational grants from: AnaptysBio, Bristol Myers Squibb, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, and UCB Pharma; all funds go to Mount Sinai Medical School.

LD, BG, SW, NC: Employees and shareholders of UCB Pharma.

BS: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, vTv Therapeutics; Stock Options: Connect Biopharma, Mindera Health; Speaker: AbbVie, Eli Lilly, Janssen, Regeneron, Sanofi Genzyme; Scientific Co-Director (consulting fee): CorEvitas (formerly Corrona) Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira, Novartis; Editor-in-Chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis.

 

Bimekizumab maintenance of response through three years in patients with moderate-to-severe plaque psoriasis who responded at Week 16: Results from the BE BRIGHT open-label extension trial

Presenters: Strober B,1,2 Tada Y,3 Mrowietz U,4 Lebwohl M,5 Foley P,6,7 Langley RG,8 Barker J,9 Wang M,10 Vanvoorden V,11 Szilagyi B,12 Ciaravino V,13 Paul C14

Affiliations: 1Yale University, USA; 2Central Connecticut Dermatology Research, USA; 3Teikyo University School of Medicine, Japan; 4University Medical Center Schleswig-Holstein, Germany; 5Icahn School of Medicine, USA; 6The University of Melbourne, Australia; 7Probity Medical Research Inc., Skin Health Institute, Australia; 8Dalhousie University, Canada; 9King’s College London, UK; 10UCB Pharma, USA; 11UCB Pharma, Belgium; 12UCB Pharma, Germany; 13UCB Pharma, France; 14Toulouse University and CHU, France

Background: Real-world studies in plaque psoriasis show only 53 to 58 percent of patients remain on a biologic therapy for three or more years,1 making it important to understand long-term efficacy of new therapies. We report maintenance of response over three years in the BE BRIGHT (NCT03598790) open-label extension (OLE) study of bimekizumab (BKZ) in patients with moderate-to-severe plaque psoriasis who had a response at Week (Wk) 16 of one of three feeder studies and entered the OLE.

Methods: All patients who completed one of the 52-wk (BE VIVID [NCT03370133]) or 56-wk (BE SURE [NCT03412747]; BE READY [NCT03410992]) Phase 3 studies were eligible to enroll in BE BRIGHT.2–4 On OLE entry, patients were assigned BKZ 320mg every four weeks (Q4W) or every eight weeks (Q8W), based on Psoriasis Area and Severity Index (PASI) response and treatment at end of feeder study. Patients were switched from BKZ Q4W to Q8W at OLE Wk24 (based on PASI response and investigator discretion) and OLE Wk48 (or next visit; mandatory).5 Maintenance of PASI≤2 among Wk16 PASI≤2 responders, and PASI100 and Dermatology Life Quality Index (DLQI) 0/1 among Wk16 PASI100 responders, are reported through three years in all BKZ-treated patients and those who received BKZ Q4W/Q8W/Q8W dosing. Data are reported as modified non-responder imputation (mNRI) and NRI.

Results: Among Wk16 PASI≤2 (N=694) and PASI100 (N=503) responders, 96.5 percent achieved PASI≤2 and 89.3 percent achieved PASI100 at one year; 94.2 percent and 82.0% percent maintained responses at three years. Among Wk16 PASI100 responders in BE SURE and BE READY (DLQI assessed on different schedule in BE VIVID), 92.0 percent achieved DLQI0/1 at one year, and 88.0 percent at three years (mNRI). At Wk16 PASI≤2 responders on Q4W/Q8W/Q8W (N=189), responses were 98.9 percent (1 year) and 96.8 percent (3 years). Of Wk16 PASI100 responders on Q4W/Q8W/Q8W (N=147), PASI100 responses were 93.6 percent and 84.4 percent, respectively, and DLQI0/1 responses were 95.8 percent and 92.5 percent (mNRI).

Conclusion: BKZ provided long-term maintenance of efficacy and health-related quality of life outcomes in patients with moderate-to-severe plaque psoriasis. A high percentage of patients who achieved disease control after 16 weeks of treatment maintained responses through three years.

Funding: Funding was provided by UCB Pharma.

Disclosures: BSt: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Ono, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; Stock options: Connect Biopharma, Mindera; Speaker: AbbVie, Eli Lilly, Janssen, Regeneron, and Sanofi Genzyme; Scientific Co-Director (consulting fee): CorEvitas (formerly Corrona) Psoriasis Registry; Investigator: AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis; Editor-in-Chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis.

YT: Honoraria and/or grants from AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Pharma. UM: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr. Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi, and UCB Pharma.

ML: Employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB Pharma; consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas (formerly Corrona), Dermavant, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. PF: Grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Evelo Biosciences, Galderma, Genentech, Geneseq, GenesisCare, GSK, Hexima, Janssen, Kymab, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma, and Valeant; served on advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Valeant; consultant for Aslan, Bristol Myers Squibb, Eli Lilly, Galderma, GenesisCare, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma, and Wintermute; received travel grants from AbbVie, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sun Pharma, and Sanofi; served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma, and Valeant. RGL: Principal Investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, and Pfizer.

JB: Within the past 5 years JB has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Samsung, Sienna, Sun Pharma, and UCB Pharma.

MW, VV, BSz: Employees and shareholders of UCB Pharma.

VC: Employee and shareholder of UCB Pharma. CP: Consulting fees and/or grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, GSK, Janssen Cilag, LEO Pharma, Eli Lilly, Novartis, Pierre Fabre, Pfizer, Sanofi Regeneron, and UCB Pharma.

 

Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: Analysis of pooled data from up to three years of treatment in Phase 2 and 3 clinical trials

Presenters: Gordon KB,1 Langley RG,2 Warren RB,3 Okubo Y,4 Rosmarin D,5 Lebwohl M,6 Peterson L,7 Madden C,7 de Cuyper D,8 Gomez NN,9 Thaçi D10

Affiliations: 1Medical College of Wisconsin, USA; 2Dalhousie University, Canada; 3Manchester NIHR Biomedical Research Centre, UK; 4Tokyo Medical University, Japan; 5Tufts Medical Center, USA; 6Icahn School of Medicine, USA; 7UCB Pharma, USA; 8UCB Pharma, Belgium; 9UCB Pharma, Germany; 10University of Lübeck, Germany

Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody used in the treatment of psoriasis which selectively inhibits interleukin (IL)-17F in addition to IL‑17A.1,2 Data pooled over two years have indicated that BKZ is generally well-tolerated.3 We report three-year BKZ pooled safety data in patients with moderate-to-severe plaque psoriasis.

Methods: Safety data were evaluated for all patients who received one or more dose BKZ in four Phase 3 trials (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE READY [NCT03410992], and their ongoing open-label extension BE BRIGHT open-label extension [NCT03598790; data cut-off: 10/23/2021]) and four Phase 2 trials (BE ABLE 1 [NCT02905006], BE ABLE 2 [NCT03010527], PS0016 [NCT03025542], PS0018 [NCT03230292]). Safety data were evaluated separately for patients receiving BKZ dosed 320mg every four weeks (Q4W) or every eight weeks (Q8W). Exposure-adjusted incidence rates (EAIRs) for treatment-emergent adverse events (TEAEs) are the incidence of new cases per 100 patient-years (PY).

Results: Total BKZ exposure was 4,245.3 PY (N=1,789) across Phase 2/3 trials, and 3,876.4 PY (N=1,495) in Phase 3 trials. TEAEs occurred at a rate of 186.1 across Phase 2/3 trials, serious TEAEs at 5.6, and TEAEs leading to discontinuation at 3.5. Eighteen deaths occurred (0.4/100 PY), all unrelated to study treatment except one (relationship unknown). TEAEs occurred less frequently in Q8W- than Q4W-treated patients in Phase 3 trials. Consistent with previous reports, most common TEAEs (EAIR) in Phase 2/3 trials were nasopharyngitis (15.3), oral candidiasis (10.2), and upper respiratory tract infection (7.1).3 EAIR of serious infections was 1.2. Most frequently reported were serious coronavirus infections (0.2). There were no cases of active tuberculosis. EAIR of oral candidiasis was 10.2, decreased vs two-year data (12.6),3 and was less common with BKZ Q8W vs Q4W. The vast majority of oral candidiasis events were mild or moderate (99.4%); none were serious. EAIRs of hepatic events (4.0) and elevated liver enzymes (3.4) were decreased vs. two-year data (4.3 and 3.6, respectively).3 EAIRs for inflammatory bowel disease (0.1), adjudicated major adverse cardiac events (0.6), and adjudicated suicidal ideation and behavior (0.1) were low. EAIRs for other safety topics of interest were also low and were similar to or lower than two-year EAIRs.3

Conclusion: BKZ was well-tolerated over three years. No safety signals were identified; EAIRs of TEAEs did not increase compared with data from two years.3

Funding: Funding was provided by UCB Pharma.

Disclosures: KBG: Received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma. 

RGL: Principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, and Pfizer. 

RBW: Received consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma; received research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma; honoraria from Astellas, DiCE, GSK, and Union; supported by the NIHR Manchester Biomedical Centre. 

YO: Received research grants from Eisai, Maruho, Shiseido, Torii; current consulting/advisory board agreements from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Sun Pharma; speakers bureau from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Jimro, Kyowa Kirin, LEO Pharma, Maruho, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, UCB Pharma; clinical trials sponsored by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Maruho, Pfizer, Sun Pharma, and UCB Pharma.

DR: Received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, VielaBio; has received research support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Merck, Novartis, Pfizer, and Regeneron; served as a paid speaker for AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, and Sanofi. 

ML: Employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB Pharma; consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas (formerly Corrona), Dermavant, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica.

LP, CM, DdC: Employees and shareholders of UCB Pharma.

NNG: Former employee and shareholder of UCB; current employee of Boehringer Ingelheim. DT: Honoraria for participation on advisory boards, as a speaker and for consultancy from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi Genzyme, and UCB Pharma; received research grants from LEO Pharma and Novartis.

 

Bimekizumab speed of response in patients with moderate-to-severe plaque psoriasis: Results from four Phase 3/3b trials (BE VIVID, BE READY, BE SURE, and BE RADIANT)

Presenters: Blauvelt A,1 Duffin KC,2 Magnolo N,3 Weisman J,4 Ståhle M,5 Wilsmann-Theis D,6 Wang M,7 Wixted K,7 Szilagyi, B8 Puig L9

Affiliations: 1Oregon Medical Research Center, USA; 2Department of Dermatology, University of Utah, Salt Lake City, Utah, USA; 3Department of Dermatology, University Hospital Münster, Münster, Germany; 4Atlanta Medical Dermatology Specialists, Inc., Atlanta, Georgia, USA; 5Department of Medicine, Karolinska Institutet, Solna, Sweden; 6University Hospital Bonn, University of Bonn, Bonn, Germany; 7UCB Pharma, USA; 8UCB Pharma, Germany; 9Universitat Autònoma de Barcelona, Spain

Background: At least 90 percent of patients (pts) with plaque psoriasis consider rapid response to be an important treatment goal, with an average expectation of complete skin clearance within four weeks (wks).1 The objectives of this study are to evaluate early clinical efficacy and health-related quality of life (HRQoL) benefit in pts with moderate-to-severe plaque psoriasis treated with bimekizumab (BKZ) vs adalimumab (ADA), ustekinumab (UST), and secukinumab (SEC) in four Phase 3/3b trials.

Methods: Data are reported in parallel from BE VIVID, BE READY, BE SURE, and BE RADIANT.2–5 Pts included were randomized to receive BKZ (320mg every four wks [Q4W]), ADA (80mg at baseline, 40mg at Wk1, then every two wks), UST (45 or 90mg at baseline and Wk4, then every 12 wks, or SEC (300mg weekly to Wk4, then Q4W). We report the proportion of pts achieving PASI75, PASI100, and DLQI0/1 at Wk4 in each trial (non-responder imputation).

Results: These analyses include 478 pts in BE SURE (BKZ: 319; ADA: 159) 484 pts in BE VIVID (BKZ: 321; UST: 163), 349 pts in BE READY (BKZ: 349), and 743 pts in BE RADIANT (BKZ: 373; SEC: 370). At Wk4, a higher proportion of BKZ-randomized pts achieved PASI75 vs active comparators (BE SURE: BKZ: 76.5%, ADA: 31.4%; BE VIVID: BKZ: 76.9%, UST: 15.3%; BE READY: BKZ: 75.9%; BE RADIANT: BKZ: 71.0%, SEC: 47.3%); all BKZ comparisons: p<0.001. At Wk4, PASI100 was achieved by more BKZ-randomized pts than active comparators (BE VIVID: BKZ: 15.0%, UST: 1.2%; BE READY: BKZ: 18.9%; BE SURE: BKZ: 15.4%, ADA: 1.3%; BE RADIANT: BKZ: 13.9%, SEC: 6.2%); all BKZ comparisons: nominal p<0.001. Furthermore, a greater proportion of BKZ-randomized pts vs active comparators achieved DLQI0/1 at Wk4 (BE VIVID: BKZ: 37.4%, UST: 11.0%; BE READY: BKZ: 43.0%; BE SURE: BKZ: 37.6%, ADA: 25.8%; BE RADIANT: BKZ: 57.9%, SEC: 40.8%); BKZ vs ADA: nominal p=0.010; all other BKZ comparisons: nominal p<0.001.

Conclusion: At Wk4, after one dose of BKZ, faster responses, greater levels of skin clearance, and more HRQoL benefits were observed compared with UST (one dose), ADA (two doses), or SEC (four doses), consistent across the four trials.

Funding: UCB Pharma provided funding for this study.

Disclosures: AB: Served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Meyers Squibb, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB Pharma; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Meyers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor; acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Meyers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma.

KCD: Received grants/investigator for AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, Sienna, Stiefel, and UCB Pharma; speakers bureau for Novartis (non-promotional only); consultant/advisory board for AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Ortho Dermatologics, Pfizer, Sienna, Stiefel, and UCB Pharma.

NM: Honoraria for participation on advisory boards, as a speaker, and for consultancy from AbbVie, Almirall, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB Pharma.

JW: Research grants from AbbVie, Amgen, Avillion, Boehringer Ingelheim, BMS, ChemoCentryx, Dermira, GSK, InflaRx, Leo Pharma, Janssen, Novartis, Pfizer, Regeneron, Sanofi, and UCB Pharma; consulting fees from AbbVie, Janssen, Novartis, Regeneron, Sanofi, and UCB Pharma; speakers bureau for AbbVie, Janssen, Novartis, Regeneron, and Sanofi. MS: Has received honoraria for participating in advisory boards and has given lectures for AbbVie, Celgene, Eli Lilly, Leo Pharma, Lipidor, Novartis, Pfizer, and UCB Pharma.

DWT: Has been an advisor for and/or received speaker’s honoraria or travel expense reimbursements from and/or received grants from and/or participated in clinical trials for AbbVie, Almirall, Amgen, Beiersdorf, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Forward Pharma, GSK, Janssen, Leo Pharma, Medac, Merck, Novartis, Pfizer, UCB Pharma, and VBL.

MW, KW, BS: Employees and shareholders of UCB Pharma.

LP: Received consultancy/speaker’s honoraria from and/or participated in trials sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Gebro, Janssen, JS BIOCAD, Leo Pharma, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Samsung-Bioepis, Sandoz, Sanofi Genzyme, and UCB Pharma.

 

Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the Phase 3 POETYK PSO program

Presenters: Lebwohl M,1 Warren RB,2 Sofen H,3 Imafuku S,4 Paul C,5 Szepietowski JC,6 Spelman L,7 Passeron T,8 Colston E,9 Hippeli L,9 Napoli A,9 Kisa RM,9 Banerjee S,9 Menter A,10 Thaçi D,11 Blauvelt A12

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Dermatology Centre, Salford Royal NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK; 3UCLA School of Medicine, Los Angeles, CA, USA; 4Fukuoka University Hospital, Fukuoka, Japan; 5Toulouse University and CHU, Toulouse, France; 6Wroclaw Medical University, Wroclaw, Poland; 7Veracity Clinical Research, Brisbane, QLD, Australia; 8Côte d’Azur University, University Hospital of Nice, Nice, France; 9Bristol Myers Squibb, Princeton, NJ, USA; 10Baylor University Medical Center, Dallas, TX, USA; 11University of Lübeck, Lübeck, Germany; 12Oregon Medical Research Center, Portland, OR, USA

Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the pivotal Phase 3 POETYK PSO-1 trial in moderate-to-severe plaque psoriasis, deucravacitinib was superior to placebo and apremilast using multiple clinical endpoints, including 75 percent or more reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement at baseline (sPGA 0/1) at Week 16. Clinical efficacy was maintained through Week 52 on continued treatment. We examined long-term clinical efficacy in patients randomized to deucravacitinib on Day 1 in PSO-1 who opted to continue treatment at Week 52 in the POETYK long-term extension (LTE) trial.

Methods: In the 52-week POETYK PSO-1 trial, adult patients with moderate-to-severe psoriasis were randomized 2:1:1 to deucravacitinib 6mg once daily, placebo, or apremilast 30 mg twice daily; upon trial completion, patients could enter the LTE and receive deucravacitinib. Efficacy endpoints included PASI 75, PASI 90, and sPGA 0/1 in deucravacitinib patients continuing treatment in the LTE. Maintenance of response was assessed in Week 16 PASI 75 responders continuing treatment in the LTE. Modified nonresponder imputation (mNRI) was used to impute missing data; patients discontinuing due to psoriasis worsening were imputed as nonresponders. Efficacy results used as-observed data and treatment failure rule imputation.

Results: Of 332 patients randomized to deucravacitinib in PSO-1, 265 completed the trial and entered the LTE, including 173 Week 16 PASI 75 responders. The mNRI population included 262 deucravacitinib patients entering the LTE, including 171 Week 16 PASI 75 responders; patients failing to reach the Week 112 assessment or discontinuing as of October 1, 2021, were excluded. At Week 112 (LTE Week 60), mNRI response rates among deucravacitinib patients entering the LTE were 82.4 percent (PASI 75), 55.2 percent (PASI 90), and 66.5 percent (sPGA 0/1). Efficacy was maintained up to 112 weeks in Week 16 PASI 75 responders continuing treatment in the LTE, including response rates for PASI 75 at Weeks 16, 52, and 112 (100%, 90.1%, 91.0%, respectively), PASI 90 (62.6%, 64.9%, 63.0%) and sPGA 0/1 (84.2%, 73.7%, 73.5%).

Conclusion: Clinical efficacy was maintained up to 112 weeks with continuous deucravacitinib treatment, further supporting deucravacitinib as an effective treatment for patients with moderate-to-severe plaque psoriasis.

Funding: This study was funded by Bristol Myers Squibb.

Disclosures: ML: Research funds on behalf of Mount Sinai: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB; Consultant: Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Arena, Aristea, Arrive Technologies, Avotres, BiomX, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Cara, Castle Biosciences, CorEvitas’ (Corrona) Psoriasis Registry, Dermavant, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Forte Biosciences, Helsinn Therapeutics, Hexima, Leo Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica

RBW: Research grants: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, DICE Therapeutics, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, UNION, and XenoPort

HS: Clinical investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma

SI: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Janssen, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin; Personal fees: Amgen (Celgene), Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB

CP: Grants and consultant: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB

JCS: Advisory board member/consultant: AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; Speaker: AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; Investigator: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRx, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, and Trevi

LS: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck (MSD), Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab

TP: Advisory board and consulting fees: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB

EC, LH, AN, RMK, and SB: Employees and shareholders: Bristol Myers Squibb

AM: Advisory board: Abbott Labs, Amgen, Boehringer Ingelheim, Janssen Biotech, Leo Pharma; Consultant: Abbott Labs, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: Abbott Labs, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: Abbott Labs, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB.

DT: Received research support and principal investigator (clinical trials): AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Eli Lilly, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, and UCB; Consultant: AbbVie, Almirall, Galapagos, Leo Pharma, Novartis, Pfizer, and UCB; Lecturer: AbbVie, Almirall, Amgen, Janssen, Eli Lilly, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution, and UCB; Scientific advisory board: AbbVie, Amgen, Eli Lilly, Janssen-Cilag, Leo Pharma, Morphosis, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB

AB: Speaker (with honoraria): AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB; Scientific adviser (with honoraria): AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB, Vibliome, and Xencor; Clinical study investigator (institution has received clinical study funds): AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB.

 

Durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-Week, Phase 2 open-label safety trial

Presenters: Lebwohl M,1 Stein Gold L,2 Gooderham MJ,3 Papp KA,4 Ferris LK,5 Adam DN,6 Hong HC,7 Kircik LH,8 Zirwas M,9 Burnett P,10 Higham R,10 Krupa D,10 Berk D10

Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Henry Ford Medical Center, Detroit, MI, USA; 3SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 4Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 5University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 6CCA Medical Research, Probity Medical Research and Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 7Probity Medical Research and University of British Columbia, Department of Dermatology and Skin Science, Surrey, BC, Canada; 8Icahn 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, USA; 9Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 10Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

Background: Roflumilast cream is a potent phosphodiesterase 4 inhibitor recently approved in the United States for treatment of plaque psoriasis with no limitations on duration of use. An open-label trial was conducted to evaluate long-term safety (52 weeks) of once-daily roflumilast cream (NCT03764475). This abstract presents data on durability of response as measured by the percentage of patients with an Investigator Global Assessment (IGA) score of Clear or Almost Clear, percentage improvement in Psoriasis Area Severity Index (PASI) score, and reduction in body surface area (BSA) affected.

Methods: Patients who completed a parent, Phase 2b, 12-week randomized controlled trial could continue on open-label roflumilast cream 0.3% (Cohort-1, n=230), and patients naïve to roflumilast were also enrolled (Cohort-2, n=102). All psoriasis lesions (except scalp) were treated, including face and intertriginous areas for up to 52 weeks. If affected, palms and soles were treated, but not evaluated towards any efficacy assessments. Median duration of response was determined using the Kaplan-Meier method.

Results: With cumulative treatment up to 64 weeks in Cohort-1 and 52 weeks in Cohort-2, long-term safety and tolerability were consistent with the 12-week, Phase 2b study. Overall, 73.5 percent of patients completed the study; 3.9 percent discontinued due to adverse events (AE) and 0.9 percent discontinued due to lack of efficacy. Treatment-related AEs were reported in 2.7 percent patients; none were deemed serious. Investigator tolerability assessments at each visit demonstrated 99 percent of patients rated “no evidence of irritation.” At Week 52, IGA Success (demonstrating Clear/Almost Clear plus 2-grade improvement from baseline) was achieved by 34.8 percent of patients in Cohort-1 and 39.5 percent in Cohort-2. Of patients in Cohort-2, 40 percent of patients achieved IGA success at Week 12. IGA Clear/Almost Clear was achieved by 46.8 percent of patients across both cohorts at Week 12 and consistent through Week 52 (44.8%). Similarly, a 60.5 percent mean PASI improvement and 60.1 percent mean BSA improvement from baseline were observed at Week 12 and consistent through Week 52 (59.4% and 63.3%, respectively). Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, the median durability of IGA of Clear/Almost Clear was 10 months (40.1 weeks). Among patients who achieved an IGA of Clear or Almost Clear, 50 percent maintained Clear or Almost Clear status for at least 10 months.

Conclusion: In this long-term safety study, roflumilast cream was well tolerated with a safety profile consistent with the parent Ph2b trial, and effectively maintained clear/almost clear skin with no tachyphylaxis observed.

Funding: Funding was provided by Arcutis Biotherapeutics, Inc.

 

Efficacy and safety of apremilast in patients with genital psoriasis: Results from the Phase 3, randomized, placebo-Controlled, double-blind DISCREET study

Presenters: Merola JF,1 Parish LC,2 Guenther L,3 Lynde C,4,5 Lacour JP,6 Staubach P,7 Cheng S,8 Jardon S,8 Paris M,8 Chen M8, Papp K9,10

Affiliations: 1Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 2Parish Dermatology, Philadelphia, PA, USA; 3Guenther Research Inc., London, ON, Canada; 4Lynde Institute for Dermatology, Markham, ON, Canada; 5Probity Medical Research, Markham, ON, Canada; 6CHU de Nice – Hôpital l’Archet, Nice, France; 7Department of Dermatology, University Medical Center, Mainz, Germany; 8Amgen Inc., Thousand Oaks, CA, USA; 9Probity Medical Research, Waterloo, ON, Canada; 10K Papp Clinical Research, Waterloo, ON, Canada;

Background: Apremilast, an oral immunomodulator, is approved in adults with psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease.

Objective: To evaluate the benefit, safety, tolerability, and effect on health-related QoL of apremilast in patients with moderate-to-severe genital psoriasis after 16 weeks of treatment in the DISCREET study (NCT03777436).

Methods: This Phase 3, multicenter study included patients with a genital psoriasis severity (modified sPGA-G) score ≥ 3; an overall psoriasis severity (sPGA) score ≥ 3; nongenital plaque psoriasis on ≥ 1% of BSA; or those who were intolerant to/or not controlled by medications applied to the skin for genital psoriasis. Patients (N=289) were randomized 1:1 to receive apremilast or placebo for 16 weeks; at Week 32, the patients receiving placebo were switched to apremilast as well. The primary outcome was a Modified sPGA-G response (score 0 [clear] or 1 [almost clear] with a ≥ 2-point reduction from baseline) to assess genital psoriasis severity at Week 16. 

Results: At Week 16, sPGA-G response rate was 38.7% in patients who received apremilast versus 19.1% in patients who received placebo; sPGA response rate was 21.5% with apremilast versus 7.2% with placebo; GPI-NRS response rate was 46.0% with apremilast versus 19.6% with placebo; and reduction in DLQI score from baseline was ­–5.3 with apremilast versus –2.6 with placebo. No new safety signals were identified, and adverse events were consistent with the known apremilast safety profile. 

Conclusion: Apremilast, the first oral treatment to be studied for genital psoriasis, significantly improved disease symptoms, including skin, itch, and QoL and was well-tolerated in patients who were inadequately controlled by or intolerant to medications applied to the skin.

Funding: This study was funded by Amgen Inc. 

Disclosures: JFM: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, and UCB – consultant and/or investigator. 

LCP: AbbVie, Alfasigma, Amgen, Amytrx, Eli Lilly, Bristol Myers Squibb, Fibrocell, Galderma, GlaxoSmithKline, Kiniksa, Olix, Oneness, Pfizer, Trevi, and UCB – investigator. 

LG: AbbVie, Amgen, Bausch Health, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck Frosst, Pfizer, Sun Pharmaceuticals, and UCB – consultant, investigator, and/or speaker. Amgen, Bausch, Eli Lilly, Janssen, LEO Pharma, Pfizer, and Sun Pharmaceuticals – speaker, consultant, and grant/research support. AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galderma, Merck Frosst, and UCB Pharma – grant/research support.

CL: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sun Pharma, and Valeant – principal investigator/consultant. 

J-PL: AbbVie, Amgen, Boehringer Ingelheim, Dermira, Janssen, LEO Pharma, and Pfizer – grants and personal fees. Celgene, Galderma, Eli Lilly, Novartis and Sanofi – grant/research support. 

PS: AbbVie, ALLERGIKA, Almirall Hermal, Amgen, Beiersdorf, BioCryst, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CSL Behring, Eli Lilly, Galderma, Hexal, Janssen, Klinge, LEO Pharma, LETI Pharma, L´Oreal, Neubourg, Novartis, Octapharma, Pfizer, Pflüger, Pharming, Regeneron, Shire, Takeda, Regeneron, Sanofi Genzyme, and UCB Pharma – grants. 

SC, SJ, MP, and MC: Amgen Inc. – employees and stockholders. KP: AbbVie, Actelion, Amgen, Astellas Pharma US, Boehringer Ingelheim, Bausch Health, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co., Inc., Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant; PSLOAR, PURE – steering committee member.

 

Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a Phase 2, randomized, double-blind, placebo-controlled study

Presenters: Werth VP,1 Pike M,2 Merrill JT,3 Morand E,4 van Vollenhoven R,5 Hobar C,6 Delev N, ,6 Shah V,6 Sharkey B6 Wegman T,6 Catlett I,6 Banerjee S,6 Singhal S6

Affiliations: 1University of Pennsylvania and the Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA; 2MedPharm Consulting, Inc, Raleigh, NC, USA; 3Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; 4Monash University, Victoria; Department of Rheumatology, Monash Health, Victoria, Australia; 5Amsterdam University Medical Centers, Amsterdam, the Netherlands; 6Bristol Myers Squibb, Princeton, NJ, USA

Background: Tyrosine kinase 2 (TYK2) mediates signaling of Type I interferons and IL-23, key cytokines involved in systemic lupus erythematosus (SLE) pathogenesis. Deucravacitinib is an oral, selective, allosteric TYK2 inhibitor with a unique mechanism of action, distinct from Janus kinase (JAK) 1/2/3 inhibitors. Deucravacitinib is approved in multiple countries for the treatment of adults with plaque psoriasis. This analysis assessed the efficacy and safety of deucravacitinib in patients with active SLE.

Methods: This was a 48-week, double-blind, placebo-controlled, Phase 2 trial (NCT03252587).1 Eligible patients met the Systemic Lupus International Collaborating Clinics (SLICC) criteria, were seropositive, and had a Systemic Lupus Erythematosus Disease Activity Index 2000 score ≥6 and ≥1 British Isles Lupus Assessment Group (BILAG) index A or ≥2 BILAG B manifestations from the musculoskeletal or mucocutaneous domain. Patients on standard background medications were randomized 1:1:1:1 to deucravacitinib (3mg BID, 6 mg BID, 12mg QD) or placebo. Oral corticosteroid tapering was required from Weeks 8–20; further tapering was optional from Weeks 32–40. The primary endpoint was the proportion of patients achieving SLE Responder Index (SRI[4]) at Week 32. Key secondary endpoints at Week 48 included the proportion of patients achieving SRI(4) and decrease of 50 percent or more from baseline Cutaneous Lupus Erythematosus Disease 2 Area and Severity Index (CLASI-50) in patients with baseline CLASI ≥10. Change from baseline in CLASI Activity Score (CLASI-A) over time was also assessed.

Results: Of 363 randomized patients, 275 (76%) completed 48 weeks of treatment. Baseline demographic and disease characteristics were balanced across treatment groups, with baseline mean CLASI-A scores ranging from 8.0–8.6 across groups. The primary endpoint at Week 32 was met, with significantly greater proportions of patients in the deucravacitinib 3mg BID and 6mg BID groups vs placebo achieving SRI4 responses (placebo: 34.4%; deucravacitinib 3 mg BID: 58.2%, P=0.0006; 6 mg BID: 49.5%, P=0.021; 12mg QD: 44.9%, P=0.078). SRI4 response was sustained across all deucravacitinib groups up to 48 weeks. At Week 48, patients treated with deucravacitinib demonstrated improvement across all secondary endpoints compared with placebo. In patients with CLASI ≥10 at baseline, greater mean changes from baseline in CLASI-A were observed in deucravacitinib vs placebo at Week 48 (placebo: 16.7%; deucravacitinib 3mg BID: 69.6%, P=0.0006; 6 mg BID: 56.0%, P=0.0058; 12mg QD: 62.1%, P=0.0009). Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between deucravacitinib and placebo groups. Most common AEs (≥10%) with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. No deaths, major adverse cardiac events, thrombotic events, systemic opportunistic infections, or active tuberculosis occurred. Malignancies were rare, with similar rates across all groups. No meaningful abnormalities in mean levels of hematology and chemistry laboratory parameters were observed.

Conclusion: Deucravacitinib demonstrated sustained, meaningful clinical efficacy in SRI,4 improvement in mucocutaneous activity as measured by CLASI-A responses, and was well tolerated in patients with active SLE up to 48 weeks. Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in Phase 3 trials.

Funding: Funding was provided by Bristol Myers Squibb.

Disclosures: VPW: Consultancy − Celgene, Medimmune, Resolve, Genentech, Idera, Janssen, Lilly, Biogen, Bristol Myers Squibb, Gilead, Amgen, Medscape, Nektar, Incyte, EMD Serono, CSL Behring, Principia, Crisalis, Viela Bio, Argenx, Kirin, AstraZeneca, AbbVie, GSK, Cugene, UCB, Corcept, and Beacon Bioscience; research support − Celgene, Janssen, Biogen, Gilead, AstraZeneca, Viela, Amgen, and Lupus Research Alliance/BMS

MP: Consultancy − AstraZeneca, Bristol Myers Squibb, and Pfizer

JTM: Consultancy − UCB, GlaxoSmithKline, AbbVie, EMD Serono, Remegen, Celgene/Bristol Myers Squibb, AstraZeneca, Amgen, Janssen, Lilly, Genentech, Aurinia, Astellas, Alexion, Sanofi, Zenas, and Provention; conduct research − GlaxoSmithKline and AstraZeneca

EM: Consultancy − AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, Servier, and Novartis; research support − AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, Janssen, and UCB

RvV: Research support − Bristol Myers Squibb, GlaxoSmithKline, and Eli Lilly; research support, consultancy, speaker − UCB; support for educational programs, consultancy, speaker − Pfizer; support for educational programs − Roche; consultancy, speaker − AbbVie, Galapagos, and Janssen; consultancy − AstraZeneca, Biogen, Biotest, Celgene, Gilead, and Servier

CH, ND, VS, TW, IC, SB, SS: Employees and shareholders − Bristol Myers Squibb

BS: Former employee and shareholder – Bristol Myers Squibb

 

Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the KEEPsAKE 1 and KEEPsAKE 2 trials

Presenters: Kristensen LE,1 Papp K,2 White D,3 Asnal, C4 Lu W,5 Soliman AM,5 Padilla B,5 Chen MM,5 Östör A6

Affiliations: 1The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark; 2K Papp Clinical Research and Probity Medical Research, Waterloo, Canada; 3Rheumatology Department, Waikato Hospital, Hamilton, New Zealand, and Waikato Clinical School, University of Auckland, Auckland, New Zealand; 4DOM Centro de Reumatología, Buenos Aires, Argentina; 5AbbVie Inc., North Chicago, United States; 6Monash University, Cabrini Hospital, and Emertius Research, Melbourne, Victoria, Australia.

Background: We evaluate Risankizumab (RZB), a monoclonal antibody specifically inhibiting IL-23, versus placebo (PBO), for efficacy and safety in adults with active PsA in the ongoing Phase 3 KEEPsAKE-1 and 2 trials.

Methods: KEEPsAKE-1 and 2 enrolled adults with active PsA and plaque or nail psoriasis. KEEPsAKE-1 patients had inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drug(csDMARD-IR). KEEPsAKE-2 enrolled csDMARD-IR and/or patients with inadequate response or intolerance to one or two biologic therapies (Bio-IR). Patients randomized 1:1 received blinded subcutaneous RZB 150 mg or PBO at weeks(W) 0, 4, and 16. At W24, all patients received open-label RZB 150 mg every 12 Wks. Efficacy and safety were analyzed in patients receiving 1 or more doses of study drug through W100. Treatment-emergent adverse events (TEAEs) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years[PYs]).

Results: At W100, patients in KEEPsSAKE-1 (RZB N=483; PBO/RZB N=481) and KEEPsAKE-2 (RZB N=224; PBO/RZB N=219) had similar results to those reported at W52. Achievement of ACR20, 50, and 70 overtime results for both studies will be presented. In KEEPsAKE-1, ACR20 at W100 was achieved by 64.3 percent and 62.1 percent of RZB and PBO/RZB patients, respectively. In KEEPsAKE-2, 57.1 percent of RZB and 52.5 percent of PBO/RZB patients achieved ACR20 at W100. In KEEPsAKE-1, 71.3 percent of RZB and 67.8 percent of PBO/RZB patients achieved PASI 90. In KEEPsAKE-2, 67.5 percent of RZB and 61.3 percent of PBO/RZB patients achieved PASI 90. Patients also maintained HAQ-DI scores in both KEEPsAKE-1 (RZB -0.41, PBO/RZB -0.36) and KEEPsAKE-2 (RZB -0.26, PBO/RZB -0.31). For patients with nail psoriasis at baseline both PGA-F scores (KEEPsAKE-1 RZB -1.4, PBO/RZB -1.3) and mNAPSI scores (KEEPsAKE-1 RZB -11.33, PBO/RZB -13.54) were maintained. Resolution of enthesitis at baseline was seen in 60.6% of RZB and 62.1 percent of PBO/RZB patients in KEEPsAKE-1 and 51.7 percent of RZB and 53.2 percent of PBO/RZB patients in KEEPsAKE-2. Resolution of dactylitis at baseline was seen in 75.4 percent of RZB and 77.9 percent of PBO/RZB KEEPsAKE-1 patients and 77.5 percent of RZB and 68.4 percent of RZB/PBO patients in KEEPsAKE-2. As of the W100 cut-off, EAERs of any TEAE was 130.1/100PY(KEEPsAKE-1) and 180.5/100PYin(KEEPsAKE-2).

Conclusion: Long term treatment with RZB provides durable efficacy response in PsA through 100 weeks. RZB was generally well tolerated, with no new safety signals.

 

Efficacy and safety results of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-Week results from SPROUT, a Phase 3, randomized, controlled study

Presenters: Fiorillo L,1 Becker E,2 de Lucas R,3 Belloni-Fortina A,4 Armesto S,5 Maes P,6 Oberoi RK,6 Paris M,6 Zhang W,6 Zhang Z,6 Arkin L7

Affiliations: 1Stollery Children’s Hospital/University of Alberta, Edmonton, Alberta, Canada; 2Driscoll Children’s Hospital, Corpus Christi, TX, USA; 3Hospital Universitario La Paz – PPDS, Madrid, Spain; 4Azienda Ospedale Università Padova, Padova, Italy; 5Hospital Universitario Marques de Valdecilla, Santander, Spain; 6Amgen Inc., Thousand Oaks, CA, USA; 7University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Background: Approved systemic therapies for moderate-to-severe plaque psoriasis (PsO) in pediatric patients are limited. Apremilast, an oral phosphodiesterase 4 inhibitor, is internationally approved for use in adults with PsO, psoriatic arthritis, and Behçet’s syndrome. We evaluated the efficacy and safety of apremilast in the treatment of pediatric patients with moderate-to-severe PsO inadequately controlled/intolerant to topical therapy.

Objective: SPROUT (NCT03701763) was a Phase 3, randomized, double-blind, placebo (PBO)-controlled study of apremilast in patients aged 6 to 17 years with moderate-to-severe PsO (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled /intolerant to topical therapy. Patients were randomized (2:1), stratified by age group to apremilast (20mg or 30mg BID based on weight) or placebo for 16 weeks, followed by apremilast active treatment extension to 52 weeks. The primary endpoint was sPGA response (score of 0/1 [clear/almost clear] with a ≥2-point reduction) at Week 16. The key secondary endpoint was the proportion of patients achieving a ≥75% reduction in PASI score from baseline (PASI-75).

Results: From December 2018 to December 2021, 245 patients were randomized (apremilast: 163; placebo: 82). Mean age was 12 years, with 41.2 percent aged 6 to 11 years and 58.8 percent aged 12 to 17 years. Mean body weight was 52kg with 49.0 percent weighing ≥20 to <50kg and 51.0 percent weighing ≥50 kg. Mean duration of PsO was four years, mean PASI score was 19.8, 75.5 percent and 24.5 percent of patients had sPGA score of three (moderate) and four (severe) at baseline, respectively. The primary endpoint (sPGA response) was met, with a treatment difference of 21.7 percent (95% CI: 11.2%, 32.1%; P<0.0001) favoring apremilast versus placebo. Additionally, a greater proportion of patients achieved PASI-75 at Week 16 with apremilast versus placebo (45.4% vs 16.1%; P<0.0001). Subgroup analyses by age and weight showed treatment effects that were consistent with the overall population. Treatment-emergent adverse events (TEAEs) were observed in 65.0% of patients in the apremilast group and 41.3% of patients in the placebo group. Few patients experienced severe (apremilast: 1.2%; placebo: 1.3%) or serious TEAEs (apremilast: 1.2%; placebo: 1.3%). The overall safety profile was consistent with prior apremilast studies. No new safety signals were identified.

Conclusion: Apremilast effectively reduced PsO severity in children aged 6 t17 years with moderate-to-severe PsO inadequately controlled/intolerant to topical therapy. No new safety signals were identified; AEs were consistent with the known apremilast safety profile.

Funding: The study was funded by Amgen Inc.

Disclosures: LF is an investigator with Amgen, Galderma, LEO Pharma, and Pfizer.

EB is a principal investigator for Amgen Inc. Pfizer, Regeneron, and Sanofi.

ABF is a consultant for AbbVie, Janssen, Novartis, Pfizer, and Sanofi.

SA is a speaker and advisory board member at Amgen Inc., Janssen, LEO Pharma, and Novartis. 

PM, RKO, MP, WZ, and ZZ are employees and stockholders at Amgen Inc.

LA received research equipment from Amgen Inc.

 

Exposure–Response analysis demonstrates response to tapinarof is driven by local Effects at sites of application

Presenters: Del Rosso J,1 Guenthner S,2 Chih-ho Hong H,3 Jett JE,4 Brown PM,4 Rubenstein DS,4 Piscitelli SC4

Affiliations: 1JDR Dermatology Research, Las Vegas, NV, USA; 2The Indiana Clinical Trials Center, Plainfield, IN, USA; 3University of British Columbia and Probity Medical Research, Surrey, BC, Canada; 4Dermavant Sciences, Inc., Morrisville, NC, USA

Background: Tapinarof is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the Food and Drug Administration for the treatment of plaque psoriasis in adults and under investigation for the treatment of plaque psoriasis in children down to two years of age, and for atopic dermatitis (AD) in adults and children down to two years of age. Tapinarof cream 1% once daily (QD) demonstrated significant efficacy versus vehicle and favorable tolerability in adults with plaque psoriasis in two 12-week trials, PSOARING 1 and 2. In PSOARING 3, the long-term extension trial, tapinarof was effective, well tolerated, and demonstrated a durable response, with approximately a 4-month remittive effect of therapy. Tapinarof cream 1% QD under maximal use conditions in patients with extensive psoriasis resulted in minimal systemic exposure. This exposure–response analysis evaluated the hypothesis stating no relationship between tapinarof plasma exposure and efficacy or safety.

Methods: Analyses included 587 patients with pharmacokinetic data across four clinical trials: a Phase 2b trial in AD with 5%–35% body surface area (BSA) involvement (NCT02564055); a Phase 2a maximal-use trial in plaque psoriasis with ≥20% BSA (NCT04042103); and the Phase 3 trials in plaque psoriasis with 3%–20% BSA, PSOARING 1 (NCT03956355) and PSOARING 2 (NCT03983980). Tapinarof was measured in plasma with a highly sensitive assay (picograms [10–12 g]/mL]). Plasma concentrations were evaluated for relationships with disease and tapinarof dose (0.5%, 1%) and application frequency (QD, twice daily). Pharmacokinetic parameters were minimum and maximum tapinarof plasma concentrations. Adverse events of special interest (AESIs) were folliculitis, contact dermatitis, and headache. Efficacy endpoints in psoriasis trials included Physician Global Assessment and Psoriasis Area and Severity Index scores. Exposure–efficacy was not assessed for AD.

Results: Tapinarof plasma exposure was low overall and undetectable in most samples. No trends in tapinarof systemic concentrations were observed regardless of disease, or concentration or frequency of topical tapinarof application. In addition, there was no relationship between systemic concentration and %BSA in a separate analysis of the maximal-use trial, with %BSA ranging from 21%–46%. There was no relationship between plasma concentrations and efficacy endpoints. Furthermore, there was no relationship between plasma exposure and AESIs of folliculitis, contact dermatitis, or headache.

Conclusion: An exposure–response analysis across four trials demonstrated no relationships between tapinarof plasma concentrations and efficacy or safety. These findings are consistent with the clinical pharmacology of tapinarof and demonstrate that the skin is the site of drug action after topical application, with minimal systemic absorption following application, and no dependence on systemic activity for therapeutic effects.

Funding: Funding was provided by Dermavant Sciences, Inc.

 

Patients’ quality of life in a Phase 4 real-world study of tildrakizumab in moderate-to-severe plaque psoriasis

Presenters: Heim J,1 Vasquez G,1 Rozzo SJ,2 Schenkel, B2 Bhatia N3

Affiliations: 1West Michigan Dermatology, Grandville, MI, USA; 2Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA; 3Therapeutics Clinical Research, San Diego, CA, USA

Background: Tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis. We describe the primary outcome of improvement in health-related quality of life (HRQoL) from a real-world study of tildrakizumab.

Methods: In this Phase 4, uncontrolled, open-label, real-world study (NCT03718299), patients with moderate-to-severe plaque psoriasis received tildrakizumab 100mg at Week (W)0, W4, and every 12 weeks thereafter up to W52. The primary outcome was Psychological General Well-Being Index (PGWBI) total score through W64 (higher scores indicate improvement); Dermatology Life Quality Index (DLQI) was also assessed (higher scores indicate greater impairment). Missing data were not imputed.

Results: Of 55 patients enrolled, 45 were assessed at W64; 50.9 percent were male and 94.5 percent were white, with mean (standard deviation [SD]) age of 48.6 (15.3) years. The mean (SD) PGWBI total score increased significantly beginning at W4, from 78.1 (14.1) at baseline to 83.2 (13.5) at W64 (P = 0.01), as did positive well-being (12.6 [3.3] to 13.8 [3.2]; P = 0.008) and general health (9.9 [2.5] to 11.5 [2.2]; P <0.001) component scores. The DLQI score (mean [SD]) improved from 9.4 (5.2) at baseline to 2.0 (2.6) at W64 (P <0.001); 62.2 percent, 93.3 percent, and 78.9 percent of patients had a DLQI score of 0 or 1, ≤5, and reduction by 5 or more points, respectively.

Conclusion: Treatment with tildrakizumab in a real-world setting significantly improved HRQoL in patients with psoriasis as measured by the PGWBI and DLQI.

Funding: This study was funded by Sun Pharma

 

Tapinarof cream 1% once daily for plaque psoriasis: improvements in quality of life and clinical efficacy in two pivotal Phase 3 trials

Presenters: Stein Gold L,1 Griffiths CEM,2 Tallman AM,3 Brown PM,3 Lebwohl MG4

Affiliations: 1Henry Ford Health System, Detroit, MI, USA; 2University of Manchester, Manchester, UK; 3Dermavant Sciences, Inc., Morrisville, NC, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA

Background: Tapinarof cream 1% once daily (QD) demonstrated statistically significant efficacy versus vehicle and was well-tolerated in adults with mild to severe plaque psoriasis in PSOARING 1 and 2, two 12-week, Phase 3 trials. In addition, significantly greater improvements in Dermatology Life Quality Index (DLQI) change from baseline at Week 12 were observed with tapinarof versus vehicle.

Objective: To evaluate correlations between the DLQI and clinical efficacy as assessed by Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI) in PSOARING 1 and 2.

Methods: Patients in PSOARING 1 and 2 were randomized to tapinarof or vehicle for 12 weeks. The DLQI is a 10-item scale where each item is rated on a 4-point scale from zero (not at all) to three (very much); lower scores indicate higher quality of life (QoL). Efficacy was evaluated using PGA and PASI. Spearman rank correlations evaluated correlations between changes in efficacy and QoL from baseline at Week 12. Analyses used observed cases and were based on the intention-to-treat population.

Results: 683 tapinarof and 342 vehicle-treated patients from PSOARING 1 and 2 were included in the analyses. At baseline, 79.2 to 83.9 percent of patients had a PGA of 3 (moderate), mean PASI of 8.9–9.1, and mean DLQI of 8.2–8.7 (moderate impact of disease on QoL) in PSOARING 1 and 2. Mean change in DLQI from baseline at Week 12 was –5.0 vs –3.0 (P<0.0001) and –4.7 vs. –1.6 (P<0.0001), with tapinarof versus vehicle in each trial, respectively. The minimal clinically important difference in DLQI of 4 was exceeded at Week 12 in the tapinarof groups. A significantly higher proportion of patients achieved a DLQI of 0 or 1 at Week 12 in the tapinarof groups versus vehicle: 47.4 percent vs 23.3 percent (P<0.0001) and 44.9 percent vs 16.1 percent (P<0.0001) in each trial, respectively; statistical significance in favor of tapinarof was observed as early as Week 4. Improvements in DLQI in the tapinarof groups at Week 12 were statistically correlated with improvements in PGA (0.28 and 0.29, P<0.0001) and PASI (0.28 and 0.40, P<0.0001) in each trial, respectively.

Conclusion: Tapinarof demonstrated rapid, clinically meaningful, and statistically significant improvements in clinical efficacy and patient-reported QoL. A large percentage of tapinarof-treated patients achieved a DLQI of 0 or 1, i.e., no negative effects of disease on QoL. Correlations between improvements in DLQI and clinical efficacy measures suggest that, beyond clinical improvements captured by the PASI and PGA, other important factors such as mental/emotional well-being and satisfaction with treatment contribute to the considerable overall improvement in QoL observed in these trials.

Funding: Dermavant Sciences Inc provided funding for this study.

 

Tapinarof inhibits the formation, cytokine production, and persistence of resident memory T cells in vitro

Presenters: Mooney N,1 Teague JE,1 Gehad AE,1 McHale K,2 Rubenstein DS,2 Clark RA1

Affiliations: 1Brigham and Women’s Hospital, Boston, MA, USA; 2Dermavant Sciences, Inc., Morrisville, NC, USA

Background: Tapinarof, a novel, first-in-class, small-molecule topical therapy with aryl hydrocarbon receptor (AhR) agonist and antioxidant activity. Tapinarof cream 1% once daily is effective in the treatment of plaque psoriasis (PsO) in adults (Phase 3 PSOARING 1, 2, and 3 trials [NCT03956355, NCT03983980, NCT04053387]) and has demonstrated efficacy in atopic dermatitis (AD) in a Phase 2b trial (NCT02564055). In cell culture experiments, tapinarof has demonstrated increased keratinocyte expression of skin barrier proteins and reduced T cell production of interleukin (IL)-17A and IL-17F. In the PSOARING 3 long-term extension trial, patients with psoriasis who achieved a Physician Global Assessment (PGA) score of 0 (clear) discontinued tapinarof and remained clear for approximately four months, defined as a PGA of 0 (clear) or 1 (almost clear) while off therapy. Tapinarof is therefore unique in its combined AhR agonist and antioxidant activity, ability to affect both immune and stromal cells in skin, topical efficacy in both PsO and AD, and induction of a durable remittive effect. The efficacy of tapinarof in both PsO and AD and its ability to induce a lasting remittive effect suggest that it targets mechanisms common to both diseases and may affect resident memory T cell (TRM) activation and/or persistence. IL-17 drives PsO lesion formation and evidence suggests that reactivation of IL-17 producing pathogenic TRM induces recurrence of lesions in the same locations after therapy is discontinued.

Objective: To characterize the effects of tapinarof on resident memory T cells.

Methods: The in vitro effects of tapinarof on cellular markers and cytokine production were assessed in human TRM differentiation assays.

Results: Tapinarof significantly reduced CD4+ CD69+CD103+ TRM generation (P=0.03) and reduced CD4 TRM production of IL-17A and TNFα. Furthermore, 3-week tapinarof treatment of TRM from healthy human skin reduced the number of surviving CD4+ CD69+CD103+ TRM by 47% and reduced the number of IL-13 producing CD4+ TRM by 44%.

Conclusion: Our results demonstrate that tapinarof reduces TRM generation, inhibits TRM Th17 and Th2 cytokine production, and inhibits the survival of CD4+ TRM. These effects of tapinarof may be responsible for its efficacy in both PSO and AD, including its ability to induce a durable remittive effect of approximately four months in patients with plaque psoriasis.

Funding: Funding for this study was provided by Dermavant Sciences Inc.


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A study of encapsulated benzoyl peroxide cream, 5%: effects on the microbiome and biophysical properties of the skin in subjects with moderate-to-severe rosacea

Presenters: Nong Y,1,5 Sugarman J,2 York JP,3 Levy-Hacham O,4 Nadora D,1 Mizrahi R,4 Galati A,1,5 Gallo, RL,6 Sivamani RK1,5,7

Affiliations: 1Integrative Skin Science and Research, Sacramento, CA; 2University of California San Francisco, San Francisco, CA; 3Galderma Laboratories LP, Dallas, TX; 4Sol-Gel, Ness Ziona, Israel; 5Pacific Skin Institute, Sacramento, CA; 6University of California San Diego, San Diego, CA; 7Department of Dermatology, University of California-Davis, Sacramento, CA

Background: Topical microencapsulated benzoyl peroxide (E-BPO) cream, 5%, is effective and well tolerated in subjects with moderate-to-severe rosacea, but its effects on the skin microbiome and biophysical properties are uncertain. In this clinical study, we evaluated whether E-BPO altered the skin microbiota in subjects with rosacea. We also tracked changes in the skin using the Investigator’s Global Assessment (IGA) tool, inflammatory grades, and erythema severity measures.

Objective: This was an 8-week, double-blind, 1:1 randomized, vehicle-controlled study on 34 subjects with moderate-to-severe rosacea. The subjects were split into two crossover treatment groups (1-2 and 2-1). Skin microbiome samples were obtained at baseline, post application, and 1, 2, 4, and 8 Weeks. The samples were analyzed using shotgun metagenomic whole-genome sequencing. The rosacea IGA score, lesion counts, erythema severity, and rosacea inflammation evaluations were performed at screening, baseline, and all post baseline visits. In addition, redness, darkness, and luminosity were measured at each visit using a Colorimeter and were assessed and recorded based on the L*a*b criteria.

Methods: This was an 8-week, double-blind, 1:1 randomized, vehicle-controlled study on 34 subjects with moderate-to-severe rosacea. The subjects were split into two crossover treatment groups (1-2 and 2-1). Skin microbiome samples were obtained at baseline, post application, and 1, 2, 4, and 8 Weeks. The samples were analyzed using shotgun metagenomic whole-genome sequencing. The rosacea IGA score, lesion counts, erythema severity, and rosacea inflammation evaluations were performed at screening, baseline, and all post baseline visits. In addition, redness, darkness, and luminosity were measured at each visit using a Colorimeter and were assessed and recorded based on the L*a*b criteria.

Results: There was a reduction in the relative abundance of Staphylococcus (P=0.1061) and an increase in Cutibacterium (P=0.0341) from baseline to Week 8 in the E-BPO group, with no noticeable changes observed in the vehicle group. There was no shift in the overall microbial diversity (Shannon diversity index) in either treatment group. For the E-BPO group, the improvement in IGA, as the percentage of subjects achieving a score equating to “clear” or “almost clear,” was higher (range: 0% to 78.57%) relative to the vehicle cream (range:0% to 37.5%) at each post baseline visit. A significant increase in the percentage of subjects with IGA success (80.00%) was observed at Week 12 in the crossover group (treatment group 2-1) when switching from vehicle to E-BPO. Similar improvements in treatment Group 2-1 were observed for the inflammatory grade (78.58%) and erythema severity (80%); the scores remained high throughout the follow-up period. Proportional L*a*b skin colorimeter measurements further supported the improved erythema results.

Conclusion: In this study, shifts in the microbiome were associated with E-BPO and correlated with rosacea improvement. E-BPO reduced the relative abundance of Staphylococcus while increasing Cutibacterium, suggesting these genera may contribute to the pathogenesis of rosacea. E-BPO demonstrated significantly sustained improvement in the severity of erythema.

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Recent Articles:

Letters to the Editor: June 2024
A Seven-week, Open-label Trial Evaluating the Safety and Efficacy of a Photopneumatic Device for Mitigating Mild-to-Moderate Acne in Healthy Adolescents and Young Adults
Energy-Based Devices for the Treatment of Facial Skin Conditions in Skin of Color
Adapting with the Pandemic: Modified Mohs Micrographic Surgery Using Rim and Deep Margin Technique
Pharmacological Management and Potentially Inappropriate Prescriptions for Patients with Acne
A Retrospective Review of a Cohort of Patients with Periorificial Dermatitis Treated with Sarecycline
Comparison of Patch Testing Results of White and Black Patients
Association Between Atopic Dermatitis and Impaired Mobility among Adults in the United States: Findings from the 2001-2006 National Health and Nutrition Examination Survey
Mantle Cell Lymphoma and Exaggerated Mosquito Bite Reactions: A New Perspective on Treatment Options
Life and Career Coaching for NPs and PAs—Navigating the New Noncompete Rule and Other 2024 Negotiation Considerations for Dermatology APPs
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