Society of Dermatology Physician Assistants: Abstracts from ... : Journal of Dermatology for Physician Assistants (2024)

Table of Contents

Tapinarof Cream 1% Once Daily is Efficacious for the Treatment of Atopic Dermatitis in Patients with Skin of Color Down to 2 Years of Age in Two Pivotal Phase 3 Trials

Andrew F. Alexis¹, Leon Kircik², Raj Chovatiya^3,4, Zakiya P. Rice⁵, Tina Bhutani⁶, Philip M. Brown⁷, Stephen C. Piscitelli⁷, David S. Rubenstein⁷, Anna M. Tallman⁷, April W. Armstrong⁸; ¹Weill Cornell Medical College, New York, NY, USA, ²Icahn School of Medicine at Mount Sinai, New York, NY, USA, ³Rosalind Franklin University, Chicago Medical School, North Chicago, IL, USA, ⁴Center for Medical Dermatology and Immunology Research, Chicago, IL, USA, ⁵Dermatology Associates of Georgia, Atlanta, GA, USA, ⁶University of California, San Francisco, CA, USA, ⁷Dermavant Sciences, Inc., Morrisville, NC, USA, ⁸University of California Los Angeles, Los Angeles, CA, USA

Introduction: Patients with atopic dermatitis (AD) and skin of color can have heterogeneous presentations and treatment responses. In the pivotal phase 3 ADORING 1 and ADORING 2 trials, tapinarof cream 1% once daily (QD) was significantly efficacious and well tolerated versus vehicle in adults and children down to 2 years of age with AD.

Objective: Here, we report analyses of efficacy by skin color in ADORING 1 and 2, based on patients’ self-identified race and investigator-assessed Fitzpatrick skin type in adults and children down to 2 years of age.

Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis^TM (vIGA-AD^TM) score of ≥3 (moderate or severe), an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. The primary efficacy endpoint was a vIGA-AD^TM score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 8. Secondary endpoints included proportion of patients with a ≥75% improvement in Eczema Area and Severity Index (EASI75).

Results: Of the 407 and 406 randomized patients, 8.8–15.3% were Asian, 26.5–35.0% were Black, 44.8–56.8% were White, and 2.7–5.2% were Other groups (including American Indian or Alaska Native, Native Hawaiian or Pacific Islander, or multiple races) across trials. Patients with Fitzpatrick skin types IV, V, and VI represented 23.8–25.1%, 20.6–22.2%, and 7.6–8.9% of patients across trials (>50% in both trials). Across trials, vIGA-AD^TM responses (ranges) for tapinarof versus vehicle were: Asian, 39.5–48.9% vs 3.7–18.5%; Black, 43.1–47.0% vs 17.5–24.1%; White, 49.4–52.1% vs 12.2–14.5%; and Other, 26.0–44.8% vs 0.0–40.2%. EASI75 responses for tapinarof versus vehicle were: Asian, 47.6–76.6% vs 17.7–20.2%; Black, 48.9–55.3% vs 25.7–30.0%; White, 61.4–67.8% vs 19.6–20.7%; and Other, 38.3–63.3% vs 0.0–40.6%. Similarly, high and consistent vIGA-AD^TM and EASI75 responses were reported with tapinarof versus vehicle in patients with Fitzpatrick skin types I–III and IV–VI.

Conclusion: Tapinarof cream 1% QD was consistently efficacious among all racial groups and Fitzpatrick skin types, including patients with skin of color, who were highly represented in these trials.

Funding Support: Dermavant Sciences, Inc.

Deucravacitinib in Plaque Psoriasis: 4-Year Safety and Efficacy Results From the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

April W. Armstrong¹, Mark Lebwohl², Richard B. Warren^3,4, Howard Sofen^1,5, Akimchi Morita⁶, Shinichi Imaf*cku⁷, Mamitaro Ohtsuki⁸, Lynda Spelman⁹, Thierry Passeron¹⁰, Kim A. Papp¹¹, Renata M. Kisa¹², Matthew J. Colombo¹², John Vaile¹², Eleni Vritzali¹², Kim Hoyt¹², Carolin Daamen¹², Subhashis Banerjee¹², Bruce Strober¹³, Diamant Thaçi¹⁴, Andrew Blauvelt¹⁵; ¹University of California Los Angeles, Los Angeles, CA, USA, ²Icahn School of Medicine at Mount Sinai, New York, NY, USA, ³Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK, ⁴NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, ⁵Dermatology Research Associates, Los Angeles, CA, USA, ⁶Nagoya City University, Nagoya, Japan, ⁷f*ckuoka University Hospital, f*ckuoka, Japan, ⁸Jichi Medical University, Tochigi, Japan, ⁹Veracity Clinical Research, Brisbane, QLD, Australia, ¹⁰Université Côte d’Azur, University Hospital of Nice, Nice, France, ¹¹Alliance Clinical Trials and Probity Medical Research, Waterloo, and University of Toronto, Toronto, ON, Canada, ¹²Bristol Myers Squibb, Princeton, NJ, USA, ¹³Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, CT, USA, ¹⁴University of Lübeck, Lübeck, Germany, ¹⁵Oregon Medical Research Center, Portland, OR, USA

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the phase 3 POETYK PSO-1 and PSO-2 trials in moderate to severe plaque psoriasis. Upon trial completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety and efficacy are reported through 4 years.

Methods: PSO-1/PSO-2 randomized patients 1:2:1 to placebo, deucravacitinib 6mg QD, or apremilast 30mg BID. At Week 52, patients in the LTE received open-label deucravacitinib 6mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials.

Results: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1- to 4-year cumulative period, respectively: AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), MACE (0.3, 0.3), and venous thromboembolism (0.2, 0.1). With continuous deucravacitinib treatment (n=513), clinical response rates were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6, 78.0]; PASI 90, 49.0% [95% CI, 44.4, 53.7]; sPGA 0/1, 55.2% [95% CI, 50.5, 59.9]) to Year 4 (PASI 75, 71.7% [95% CI, 67.0, 76.3]; PASI 90, 47.5% [95% CI, 42.6, 52.4]; sPGA 0/1, 57.2% [95% CI, 52.1, 62.2]) by mNRI.

Conclusion: Deucravacitinib demonstrated durable efficacy with continuous treatment and a safety profile through 4 years consistent with that at 3 years, without new or long-term safety signals.

Lebrikizumab Is an Effective Treatment For Moderate-to-Severe Atopic Dermatitis in Patients ≥60 Years of Age

April Armstrong¹, Matthew Zirwas², Maddalena Napolitano³, Tiago Torres⁴, Delphine Staumont-Salle⁵, Amber Reck Atwater⁶, Martin Dossenbach⁶, Helena Agell⁷, Sherry Chen⁸, Meihua Qiao⁸, Evangeline Pierce⁶, Maria Lucia Buziqui Piruzeli⁶, Arash Mostaghimi⁹; ¹University of California Los Angeles (UCLA), Los Angeles USA, ²Bexley Dermatology Research Clinic Bexley, USA, ³University of Naples Federico II, Naples, Italy, ⁴University of Porto, Portugal, ⁵Lille Inflammation Translational Research Institute (INFINITE), Lille, France, ⁶Eli Lilly and Company, Indianapolis, USA, ⁷Almirall S.A, Barcelona, Spain, ⁸Tigermed, Somerset, USA, ⁹Brigham and Women’s Hospital, USA

Introduction: Lebrikizumab (LEB) is a high-affinity monoclonal antibody which targets IL-13, the key cytokine implicated in AD. This analysis investigated the efficacy and safety of LEB in adults ≥60 years with moderate-to-severe AD.

Methods: Data was pooled from two Phase 3 trials, ADvocate1 and ADvocate2 and included 98 patients (≥60y; N=28 placebo (PBO), N=70 LEB). Patients were treated with lebrikizumab 250mg every 2 weeks or PBO, for 16 Weeks. Efficacy was assessed in the pooled modified intent to treat population at Week 16 with Investigator’s Global Assessment (IGA) (0,1) with ≥2-point improvement, ≥75% improvement in Eczema Area and Severity Index (EASI 75), EASI percentage change from baseline (CFB), and Pruritus Numeric Rating Scale (NRS) ≥4-point improvement. Categorical outcomes were evaluated by Cochran Mantel Haenszel tests to compare treatment groups. Continuous outcomes were analyzed using the analysis of covariance model. Data collected after use of rescue medication or discontinuation due to lack of efficacy were imputed with non-responder imputation (NRI) for categorical endpoints, or baseline values for continuous endpoints. Safety was also assessed in the integrated modified safety population.

Results: The baseline mean (standard deviation [SD]) age was 67.2 (6.7) years in LEB- treated patients and 69 (6.2) in PBO. The LEB-treated population was 62.9% male (n=44/70) vs PBO 46.4% (n=13/28). Race was comparable between groups. At baseline 67.1% LEB (n=47/70) and 57.1% PBO (n=16/28) patients had IGA 3, while 32.9% LEB (n=23/70) and 42.9% PBO (n=12/28) had IGA 4. Other baseline characteristics were comparable: EASI: LEB 26.1, [10.6] vs PBO 27.1, [8.1]; BSA: LEB 38.3, [19.8] vs. PBO 40.9, [18.1]; and Pruritus NRS: LEB 7.5, [2.0] vs PBO 7.4, [1.7].

At Week 16, IGA (0,1) was achieved by 34.5% LEB-treated patients vs 11% PBO (P=0.022). EASI 75 was achieved by 48.9% and 16.3% of LEB- and PBO-treated patients, respectively (P=0.004). Pruritus NRS with ≥4-point improvement was reported by 45.5% and 12.2% of LEB vs PBO, respectively (P=0.004). The mean percent CFB EASI was LEB −58.5% (SE 8.5) and PBO −29.4% (SE 11.1) (P=0.002). Safety results in the older adult population were consistent with the overall modified safety population.

Conclusion: At Week 16, efficacy and patient reported outcome endpoints were met in the older adult population. These results indicate that lebrikizumab is an effective treatment for moderate-to-severe AD in the adult population ≥60 years of age and has a consistent safety profile.

Disclosure: Presented at Maui Derm for Dermatologists.

Roflumilast Foam 0.3% Once Daily in Patients with Seborrheic Dermatitis: Improvement in Pruritus and Other Patient Reported Outcomes from a Phase 3 Trial (STRATUM)

Neal Bhatia¹, Fran Cook-Bolden², Janet DuBois³, Laura Ferris⁴, Linda Stein Gold⁵, Irina Turchin⁶, Matthew Zirwas⁷, David Krupa⁸, Patrick Burnett⁸, David R. Berk⁸, David H. Chu⁸; ¹Therapeutics Clinical Research, San Diego, California, USA, ²Park South Medical, Bronx, NY, USA, ³DermResearch, Inc., Austin, TX, USA, ⁴University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA, ⁵Henry Ford Medical Center, Detroit, MI, USA, ⁶Brunswick Dermatology Center, Fredericton, NB, Canada, ⁷Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA, ⁸Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA.

Introduction: Roflumilast is a nonsteroidal, highly potent phosphodiesterase 4 inhibitor developed as once-daily cream and foam formulations being studied in patients for long-term treatment of atopic dermatitis and seborrheic dermatitis (SD). Roflumilast cream 0.3% is approved as a once-daily, nonsteroidal cream for patients with chronic plaque psoriasis, including sensitive areas such as intertriginous, face, and genital areas. Efficacy and safety of once-daily roflumilast foam 0.3% in patients ≥9 years old with at least moderate SD from this phase 3 randomized controlled trial (NCT04973228) were reported previously. Roflumilast foam 0.3% (n=304) demonstrated statistically significant improvements in efficacy compared with vehicle (n=153) with low rates of adverse events, which were similar between treatment groups.

Methods: Here we report the patient-reported outcomes: Worst Itch Numeric Rating Scale (WI-NRS), Scalpdex, and Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI), and local tolerability.

Results: Among patients with baseline WI-NRS score ≥2, more roflumilast-treated than vehicle-treated achieved WI-NRS score 0/1 at Week 8 (70.7% vs. 52.9%; P=0.0085), with improvements in itch compared to vehicle as early as 48 hours after first treatment (mean percent change from baseline [CfB]: −27.87% vs. −13.11%; nominal P=0.0024). Roflumilast-treated patients reported greater improvements in least squares (LS) mean CfB DLQI score (−3.8 vs. −2.7; nominal P<0.001), while those with scalp involvement, had greater improvements in LS mean CfB Scalpdex score (−23.21 vs. −15.42; nominal P<0.001) at Week 8. Local tolerability and safety were favorable.

Conclusion: Treatment with once-daily roflumilast foam 0.3% reduced pruritus and improved quality of life with favorable tolerability.

Funding: Sponsored by Arcutis Biotherapeutics, Inc.

Efficacy of Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 (TYK2) Inhibitor, in Scalp Psoriasis by Baseline Psoriasis Area and Severity Index (PASI) and Baseline Body Surface Area (BSA): A Subanalysis of the Phase 3 Clinical Trial Data

Andrew Blauvelt¹, Howard Sofen², Jo Lambert³, Joseph F. Merola⁴, Mark Lebwohl⁵, Kim Hoyt⁶, Renata M. Kisa⁶, Subhashis Banerjee⁶, Thomas Scharnitz⁶, Jeffrey J. Crowley⁷; ¹Oregon Medical Research Center, Portland, OR, USA, ²University of California Los Angeles and Dermatology Research Associates, Los Angeles, CA, USA, ³Ghent University, Ghent, Belgium, ⁴UT Southwestern Medical Center, Dallas, TX, USA, ⁵Icahn School of Medicine at Mount Sinai, New York NY, USA, ⁶Bristol Myers Squibb, Princeton, NJ, USA, ⁷Bakersfield Dermatology, Bakersfield, CA, USA

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was effective and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials. Here, the efficacy of deucravacitinib in scalp psoriasis was evaluated by baseline severity of psoriasis in the trial patients with scalp involvement.

Methods: Patients with moderate to severe scalp involvement (scalp-specific Physician Global Assessment [ss-PGA] ≥3) at baseline were included in this analysis. Efficacy outcomes (ss-PGA 0/1 and Psoriasis Scalp Severity Index [PSSI] 90) were reported through Week 24 (pooled PSO-1/PSO-2, before PSO-2 rerandomization, n=514) and Week 52 (PSO-1, continuous deucravacitinib treatment, n=192). Outcomes were stratified by baseline PASI score 12-<15 (low) or ≥15 (high) and baseline BSA involvement 10%-≤15% (low) or >15% (high).

Results: ss-PGA 0/1 response rates were high and slightly greater in the high versus low PASI subgroup at Week 24 (65.8% and 58.3%, respectively) and Week 52 (73.5% and 60.0%). Similarly, PSSI 90 response rates were high and also somewhat greater in the high versus low PASI subgroup at Week 24 (55.3% and 45.8%) and Week 52 (66.0% and 53.3%). Across the 2 baseline BSA subgroups, ss-PGA 0/1 and PSSI 90 response rates were comparable at Weeks 24 and 52.

Conclusion: Deucravacitinib treatment was effective in patients with scalp involvement in psoriasis regardless of overall baseline disease severity.

Efficacy and Safety of Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Black Participants with Moderate-to-Severe Acne

Valerie D. Callender, MD^1,2, Andrew F. Alexis, MD, MPH³, Neal Bhatia, MD⁴, Julie C. Harper, MD⁵, Hilary Baldwin, MD^6,7; ¹Callender Dermatology and Cosmetic Center, Glenn Dale, MD, ²Howard University College of Medicine, Washington DC, ³Weill Cornell Medical College, New York, NY, ⁴Therapeutics Clinical Research, San Diego, CA, ⁵Dermatology & Skin Care Center of Birmingham, Birmingham, AL, ⁶The Acne Treatment and Research Center, Brooklyn, NY, ⁷Robert Wood Johnson University Hospital, New Brunswick, NJ.

Introduction: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose, triple-combination formulation approved for the treatment of acne, and is indicated in patients twelve years of age and older. In three clinical studies of participants with moderate-to-severe acne, CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety/tolerability.^1-5 To better understand the efficacy and safety of CAB gel in patients with darker skin phototypes, this post hoc analysis included participants who self-identified as ‘Black or African American’ (hereafter referred to as Black).

Methods: Data were pooled from a phase 2 (N=741) and two phase 3 (N=183; N=180), double-blind, randomized, 12-week studies. Participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle gel. Endpoints included ≥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/ noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were also assessed.

Results: Of 657 participants randomized to CAB or vehicle gel, 104 (15.8%) self-identified as Black (n=64 CAB, n=40 vehicle). At week 12, 31.5% of Black participants treated with CAB achieved treatment success, compared to 17.3% with vehicle. Inflammatory lesion reductions with CAB were significantly greater than with vehicle (−69.0% vs. −53.6%, P<0.01), and noninflammatory lesion reductions were numerically greater with CAB than with vehicle (−58.3% vs −51.9%). The rate of TEAEs with CAB treatment in Black participants was generally lower than in the overall study population (23.4% vs 24.6-36.2%),^1-5 and most TEAEs were of mild-to-moderate severity.

Conclusions: Fixed-dose, triple-combination CAB gel was efficacious and well tolerated in Black participants with moderate-to-severe acne. Despite the limited number of self-identified Black participants across the clinical studies of CAB gel, these post hoc analyses add valuable information to the limited literature describing treatment effects of fixed-dose combination acne treatments in Black individuals.

References:

Stein Gold L, et al. Am J Clin Dermatol. 2021; 23(1):93-104.
ClinicalTrials.gov: A Phase 2, Multicenter, Randomized, Double-Blind, Vehicle Controlled, Parallel-Group, Clinical Study in the Treatment of Acne Vulgaris. https://classic.clinicaltrials.gov/ct2/show/NCT03170388
Stein Gold L, et al. J Am Acad Dermatol. 2023;89(5):927-935.
Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris. https://classic.clinicaltrials.gov/ct2/show/NCT04214652.
ClinicalTrials.gov: Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris. https://classic.clinicaltrials.gov/ct2/show/NCT04214639.

Funding: Ortho Dermatologics.

Therapeutic Recommendations for the Treatment of Acne Vulgaris in the US

James Q. Del Rosso, DO^1-3, Leon H. Kircik, MD⁴, Emil A. Tanghetti, MD⁵, Zoe D. Draelos, MD⁶, April Armstrong, MD, MPH⁷, Valerie D. Callender, MD⁸, Neal Bhatia, MD⁹, Steven R. Feldman, MD, PhD¹⁰; ¹JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, ²Advanced Dermatology and Cosmetic Surgery, Maitland, FL, ³Touro University Nevada, Henderson, NV, ⁴Indiana University School of Medicine, Indianapolis, IN, ⁵Center for Dermatology and Laser Surgery, Sacramento, CA, ⁶Dermatology Consulting Services, PLLC, High Point, NC, ⁷Division of Dermatology, University of Los Angeles, Los Angeles, CA, ⁸Callender Dermatology and Cosmetic Center, Glenn Dale, MD, ⁹Therapeutics Clinical Research, San Diego, CA, ¹⁰Wake Forest University School of Medicine, Winston-Salem, NC

Introduction: Acne vulgaris and related sequelae negatively impact quality of life and are associated with increased rates of anxiety and depression. However, treatment of acne can be difficult due to its long time course, chronicity, and low patient adherence. While national acne guidelines have been recently updated, there is a need for practical, easy-to-use guidance for healthcare practitioners who treat patients with acne.

Methods: A roundtable discussion with a panel of eight clinicians and dermatologists was held to provide recommendations for the diagnosis and treatment of acne, including appropriate pharmaceutical treatments based on clinical presentation and patient population, patient discussion points, and advice for clinicians regarding acne treatment.

Results: The consensus was that successful acne treatment is contingent upon meeting three core goals: 1) correct diagnosis; 2) proper treatment regimen; and 3) patient adherence and education.

1: Acne should be diagnosed using both quantitative and qualitative assessments, taking into consideration the patient’s lived experience with acne. Quantitative assessments include acne duration; lesion type and location; inflammation; acne-related sequelae; and family history of scarring. Qualitative assessments determine how bothersome acne and/or sequelae are to patients and how much they impact quality of life. Differential diagnoses should be performed to rule out acneiform lesions, genetic disorders, infections, and certain types of medications.

2: For most patients, a combination topical treatment containing benzoyl peroxide and a retinoid and/or an antibiotic is recommended to address the multiple acne pathological processes, though sequelae and patient characteristics should be considered (eg, post-inflammatory hyperpigmentation in patients with skin of color). Fixed-dose combinations are preferred to ensure proper skin coverage, simplify treatment complexity, and improve adherence.

3: For optimal outcomes, patients should be educated about their treatments and consequences of non-adherence; realistic treatment goals should be established to manage patient expectations. A patient handout on skin care best practices can be used to detail their overall skin care regimen, treatments, and subsequent visits.

Conclusions: This practical guidance aims to assist clinicians in the successful diagnosis and treatment of acne as well as patient management/education.

Funding: Ortho Dermatologics

Efficacy and Safety of Fixed-Dose Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne Vulgaris in Children and Adolescents

Lawrence F. Eichenfield, MD¹, Adelaide A. Hebert, MD², Julie C. Harper, MD³, Hilary Baldwin, MD⁴, Neal Bhatia, MD⁵, Linda Stein Gold, MD⁶, Leon H. Kirck, MD⁷, Emmy Graber, MD, MBA⁸, Emil A. Tanghetti, MD⁹, Andrew F. Alexis, MD, MPH¹⁰, James Q. Del Rosso, DO¹¹; ¹University of California, San Diego School of Medicine, La Jolla, CA, ²UTHealth McGovern Medical School Houston, Houston, TX, ³Dermatology & Skin Care Center of Birmingham, Birmingham, AL, ⁴The Acne Treatment and Research Center, Brooklyn, NY, ⁵Therapeutics Clinical Research, San Diego, CA, ⁶Henry Ford Hospital, Detroit, MI, ⁷Icahn School of Medicine at Mount Sinai, New York, NY, ⁸The Dermatology Institute of Boston, Boston, MA, ⁹Center for Dermatology and Laser Surgery, Sacramento, CA, ¹⁰Weill Cornell Medical College, New York, NY, ¹¹JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV

Background: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose triple-combination formulation approved for acne vulgaris and is indicated for use in patients aged 12 years and older. As topical acne treatment in pediatric patients may be complicated by tolerability issues and/or a perceived lack of efficacy, the objective of this post hoc analysis was to investigate the efficacy and safety of CAB in children and adolescents.

Methods: Data were pooled from two phase 3 double-blind, randomized, 12-week studies (NCT04214639; NCT04214652). Eligible participants ≥9 years of age with moderate-to-severe acne were randomized (2:1) to once-daily CAB or vehicle gel. This analysis evaluated adolescents aged 12-17 years (CAB: n=123; vehicle: n=50). Endpoints included ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success), least-squares mean percent change from baseline in inflammatory/noninflammatory lesions, and treatment-emergent adverse events (TEAEs). Descriptive efficacy and safety data for five children aged 10-11 years enrolled in the study are also summarized (CAB: n=3; vehicle: n=2).

Results: At week 12, 51.5% of CAB–treated participants aged ≥12 years achieved treatment success vs 24.9% with vehicle gel (P<0.01). CAB treatment resulted in significant reductions of >70% in inflammatory and noninflammatory lesion counts in adolescents (78.3% and 73.7%, respectively) vs vehicle (50.5% and 42.9%; P<0.001, both). Most TEAEs were of mild-to-moderate severity, and the most common (>3% in any treatment) treatment-related TEAE was application site pain. Less than 2.5% of participants withdrew due to AEs. For the 5 children aged <12 years, all 3 treated with CAB achieved treatment success, with reductions in inflammatory/noninflammatory lesions ranging from 76%-100%; neither vehicle-treated participant achieved treatment success. Only one CAB–treated younger participant experienced TEAEs (application site pain/dryness, and erythema [all mild/moderate]) and none discontinued the study.

Conclusions: In two pooled phase 3 studies, once-daily CAB gel—the first approved fixed-dose, triple-combination topical formulation for acne vulgaris—was well tolerated and efficacious in pediatric participants with moderate-to-severe acne, with over half achieving treatment success at week 12.

Funding: Ortho Dermatologics.

Efficacy and Safety of Once-Daily Roflumilast Cream 0.05% in Pediatric Patients 2 to 5 Years of Age with Mild to Moderate Atopic Dermatitis (INTEGUMENT-PED): A Phase 3 Randomized Controlled Trial

Lawrence Eichenfield¹, John Browning², Tracy Funk³, Mercedes E. Gonzalez⁴, Adelaide A. Hebert⁵, Mark Lee⁶, Vimal H. Prajapati⁷, Rocco Serrao⁸, Lisa Swanson⁹, Robert Higham¹⁰, David Berk¹⁰; ¹University of California San Diego, San Diego, CA, USA, ²Texas Dermatology and Laser Specialists, San Antonio, TX, USA, ³Oregon Health and Science University, Portland, OR, USA, ⁴Pediatric Skin Research, LLC, Coral Gables, FL, USA, ⁵UT Health McGovern Medical School, Houston, TX, USA, ⁶Progressive Clinical Research, San Antonio, TX, USA, ⁷Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada; Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Dermatology Research Institute, Calgary, AB, Canada; Skin Health & Wellness Centre, Calgary, AB, Canada; Probity Medical Research, Calgary, AB, Canada, ⁸Dermatologists of Central States, Kettering, OH, USA, ⁹Ada West Dermatology, Meridian, ID, USA, ¹⁰Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

Background: Roflumilast is a highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily cream for atopic dermatitis (AD).

Methods: INTEGUMENT-PED (NCT04845620) was a Phase 3 parallel-group, double-blind, vehicle-controlled trial. Children aged 2 to 5 years with mild to moderate AD were treated with roflumilast cream 0.05% (n=437) or vehicle (n=215) once-daily for 4 weeks. The primary efficacy endpoint was validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) Success (defined as a score of 0 [clear] or 1 [almost clear] with 2-grade improvement from baseline) at Week 4. Secondary endpoints included 75% improvement in Eczema Area and Severity Index (EASI-75). Worst-Itch-Numeric Rating Score (WI-NRS) Success (≥4-point improvement in patients with baseline ≥4), safety, and tolerability were also assessed.

Results: At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (25.4% vs 10.7%; P<0.0001), EASI-75 (39.4% vs 20.6%; P<0.0001), and WI-NRS Success (35.3% vs 18.0%; nominal P=0.0002). Improvement in pruritus was observed by 24 hours after first application (nominal P=0.0014 versus vehicle). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with 98.9% assessed as mild to moderate. AEs occurring in >2% of patients and greater in the roflumilast-treated group were upper respiratory tract infection, diarrhea, and vomiting. For local tolerability, >92% of roflumilast-treated patients reported no or mild sensation across arms at any timepoint.

Conclusion: In this phase 3 trial, once-daily roflumilast cream 0.05% improved AD in pediatric patients (2 to 5y of age), while demonstrating favorable safety and tolerability.

Funding: Sponsored by Arcutis Biotherapeutics, Inc.

A Phase 2b, Long-term Extension, Dose-ranging Study of Oral JNJ-77242113 for the Treatment of Moderate-to-Severe Plaque Psoriasis: FRONTIER-2

Laura Korb Ferris¹, Jerry Bage^l,2, Yu-Huei Huang³, Andrew Pink⁴, Stephen K. Tyring⁵, Georgios Kokolakis⁶, Amy M. DeLozier⁷, Shu Li⁸, Yaung-Kaung Shen⁸, Takayuki Ota⁷, Robert Bissonnette⁹; ¹University of Pittsburgh, Pittsburgh, PA, USA, ²Psoriasis Treatment Center of Central NJ, East Windsor, NJ, USA, ³Department of Dermatology at Chang Gung Memorial Hospital and the School of Medicine at Chang Gung University, Taoyuan City, Taiwan, ⁴NHS Foundation Trust Great Maze Pond, London, England, ⁵Center for Clinical Studies, Webster, TX, USA, ⁶Psoriasis Research and Treatment Center, Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, ⁷Janssen Research & Development, San Diego, CA, USA, ⁸Janssen Research & Development, Spring House, PA, USA, ⁹Innovaderm Research, Montreal, Quebec, Canada

Introduction: JNJ-77242113, a targeted oral peptide, inhibits interleukin (IL)-23 signaling by binding the IL-23 receptor. JNJ-77242113 showed superior efficacy vs placebo (PBO) in moderate-to-severe psoriasis in FRONTIER-1¹. FRONTIER-2 was a phase 2b, long-term extension study, during which patients from FRONTIER-1 who entered the long-term extension were evaluated over a period of 1 year.

Procedure: FRONTIER-1 randomized patients 1:1:1:1:1:1 to JNJ-77242113 25mg daily (QD), 25mg twice daily (BID), 50mg QD, 100mg QD, 100mg BID; or PBO through Week (W)16. In FRONTIER-2, patients completing FRONTIER-1 (W16) continued assigned dose through W52; those randomized to PBO crossed over to JNJ-77242113 100mg QD (PBO→100mg). The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at W52. The response rates were estimated using non-responder imputation and FRONTIER-1 baseline data.

Results: At W52, the proportions of patients achieving PASI 75 were JNJ-77242113: 25mg QD 48.8%, 25mg BID 58.5%, 50mg QD 69.8%, 100mg QD 65.1%, 100mg BID 76.2%, and PBO→100mg 65.7%; corresponding rates for ≥90% improvement in PASI (PASI 90)/100% improvement in PASI (PASI 100) were 27.9%/14.0%, 36.6%/17.1%, 41.9%/20.9%, 51.2%/25.6%, 64.3%/40.5%, 57.1%/34.3%, respectively. The proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and IGA 0 were JNJ-77242113: 25mg QD 37.2%/14.0%, 25mg BID 46.3%/19.5%, 50mg QD 60.5%/23.3%, 100mg QD 60.5%/30.2%, 100mg BID 73.8%/42.9%, PBO→100mg 65.7%/31.4%. Across treatment groups, 58.6% of patients experienced adverse events (AEs), with no evidence of dose-dependent increase in AEs, including gastrointestinal disorders. Serious AEs were considered unrelated to study treatment by the investigators.

Conclusion: In patients with psoriasis receiving JNJ-77242113, the first targeted oral peptide to selectively block IL-23 pathway signaling, rates of near-complete/complete skin clearance from FRONTIER-11 were maintained through W52; 100mg BID yielded the highest response rates. Consistent with prior studies, no safety signals were identified.

Reference:

Bissonnette R, et al. 25th World Congress of Dermatology; July 3-8, 2023; Singapore.

Efficacy and Safety of Apremilast in Pediatric Patients with Moderate-to-Severe Plaque Psoriasis: 52-week Results from the SPROUT Randomized Controlled Trial

Loretta Fiorillo, MD¹, Emily Becker, MD², Susana Armesto, MD³, Amy S. Paller, MD⁴, Apostolos Kontzias, MD⁵, Rajneet K. Oberoi, BPharm, PhD⁵, Yuri Klyachkin, PhD⁵, Hamid Amouzadeh, PhD⁵, Zuoshun Zhang, PhD⁵, Lisa Arkin, MD⁶; ¹Stollery Children’s Hospital University of Alberta, Edmonton, Alberta, Canada, ²Driscoll Children’s Hospital, Corpus Christi, TX, USA, ³Hospital Universitario Marques de Valdecilla, Santander, Spain, ⁴Northwestern University Feinberg School of Medicine, Chicago, IL, USA, ⁵Amgen Inc., Thousand Oaks, CA, USA, ⁶University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Introduction: Systemic treatment options are limited for pediatric patients with moderate-to-severe plaque psoriasis (PsO). Apremilast is an oral phosphodiesterase-4 inhibitor approved for the treatment of PsO in adults. The SPROUT trial evaluated the efficacy and safety of apremilast over 52 weeks in pediatric patients with moderate-to-severe PsO.

Methods: SPROUT (NCT03701763) was a phase 3, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6–17 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 by or inappropriate for topical therapy. Patients were stratified by age and randomized (2:1) to apremilast (weight-based; 20mg or 30mg; twice-a-day) or placebo for 16 weeks, after which all patients continued to receive apremilast through week 52 (APR/APR) or switched from placebo to apremilast (PBO/APR). At week 16, primary (sPGA response: 33.1% vs 11.5%) and major secondary (PASI-75: 45.4% vs 16.1%) endpoints were met (P<0.0001).¹ Here we report 52-week sPGA, PASI-75, and safety results.

Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 221 (apremilast: 149 [91.4%]; placebo: 72 [87.8%]) completed the 16-week placebo-controlled period and 186 (apremilast: 125 [76.7%]; placebo: 61 [74.4%]) completed the 36-week extension. At week 52, 56.3% of APR/APR patients achieved sPGA response and 71.4% achieved PASI-75, demonstrating continued improvement from weeks 16 through 52. PBO/APR patients also achieved sPGA response (52.5%) and PASI-75 (75.4%). The safety profile was consistent with prior apremilast studies in adults. Most common treatment-emergent adverse events were gastrointestinal in nature and transient, resolving within 30 days. Apremilast pharmaco*kinetic profiles were similar regardless of randomized treatment group or weight-based dose.

Conclusion: Improvements in psoriasis severity and skin involvement were observed in pediatric patients treated with apremilast for 52 weeks. Adverse events reflected the known apremilast safety profile.

Reference:

Fiorillo L, et al. JAAD, 2023;90(3):P485-493. https://doi.org/10.1016/j.jaad.2023.10.020

The Impact of Body Mass Index on Treatment Response to Secukinumab for Patients With Hidradenitis Suppurativa: A Post-Hoc Analysis of the SUNSHINE and SUNRISE Trials

Amit Garg¹, Afsaneh Alavi², Farida Benhadou³, Angel S. Byrd⁴, Vincenzo Bettoli⁵, Ryan Sullivan⁶, Ivette Alarcon⁷, Iryna Lobach⁷, Christine-Elke Ortmann⁷, Magdalena B. Wozniak⁸, Raja Sivamani^9,10,11,12; ¹Northwell Health; New Hyde Park, NY, USA, ²Department of Dermatology, Mayo Clinic, Rochester, MN, USA, ³Department of Dermatology, Hôpitaux Universitaires de Bruxelles, Université libre de Bruxelles (ULB), Brussels, Belgium, ⁴Department of Dermatology, Howard University College of Medicine, Washington, D.C., USA, ⁵Department of Medical Sciences, O.U. of Dermatology, Azienda Ospedaliera - University of Ferrara, Ferrara, Italy, ⁶Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, ⁷Novartis Pharma AG, Basel, Switzerland, ⁸Novartis Ireland Ltd, Dublin, Ireland, ⁹Integrative Skin Science and Research, Sacramento, California, USA, ¹⁰Zen Dermatology, Sacramento, California, USA, ¹¹Department of Dermatology, University of California-Davis, Sacramento, California, USA, ¹²College of Medicine, California Northstate University, Elk Grove, California, USA.

Introduction: To evaluate the efficacy and safety of secukinumab at 16 and 52 weeks in patients with moderate-to-severe hidradenitis suppurativa (HS) grouped by BMI.

Study overview: This post-hoc analysis evaluated participants from the phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials by baseline BMI subgroups (underweight/healthy weight, <25kg/m²; overweight/obese, ≥25kg/m²). Through Week 16, patients received either secukinumab 300mg every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo (PBO); after Week 16, all patients received either dose of secukinumab.¹ Efficacy was evaluated through Week 52 using Hidradenitis Suppurativa Clinical Response (HiSCR) 50 and abscess and inflammatory nodule (AN) count. Safety was evaluated by incidence of adverse events.

Results: Of 1083 evaluable patients, 189 (17.5%) were underweight/had a healthy weight, and 894 (82.5%) were overweight/obese. Achievement of HiSCR50 at Week 16 was numerically greater in patients receiving SECQ2W or SECQ4W compared with PBO, respectively, in underweight/healthy weight (46.6%, 44.6%, 39.1%) and overweight/obese (45.0%, 44.4%, 32.4%) groups. Greater improvements in AN count among patients receiving SECQ2W or SECQ4W compared with PBO, respectively, were observed for both underweight/healthy weight patients (−56.3%, −39.0%, −23.6%) and overweight/obese patients (−43.7%, −45.8%, −24.0%) at Week 16. Improvements from secukinumab increased through Week 52. Similar safety was observed across BMI subgroups through Week 52.

Conclusions: Across BMI subgroups, secukinumab was effective in improving HS disease activity vs PBO at Week 16. Treatment responses were sustained or improved through Week 52, and the safety profile was consistent across subgroups.

Reference:

Kimball AB, et al. Lancet. 2023;401:747–761.

Bimekizumab Safety and Tolerability in Moderate to Severe Plaque Psoriasis: Pooled Analysis from up to 4 years of Treatment in 5 Phase 3/3b Clinical Trials

Gordon K.B.¹, Thaçi D.², Gooderham M.³, Okubo Y.⁴, Strober B.^5,6, Peterson L.⁷, Deherder D.⁸, López Pinto J.M.⁹, Gisondi P.¹⁰, ¹Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA, ²Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany, ³SKiN Centre for Dermatology, Probity Medical Research, Peterborough, ON, Canada, and Queen’s University, Kingston, ON, Canada, ⁴Department of Dermatology, Tokyo Medical University, Tokyo, Japan, ⁵Department of Dermatology, Yale University, New Haven, CT, USA, ⁶Central Connecticut Dermatology Research, Cromwell, CT, USA, ⁷UCB Pharma, Morrisville, NC, USA, ⁸UCB Pharma, Braine-l’Alleud, Belgium, ⁹UCB Pharma, Madrid, Spain, ¹⁰Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy

Introduction: Psoriasis is a chronic condition requiring long-term management; evaluating long-term safety of treatments is important. We report the first 4-year (yr) safety data for bimekizumab (BKZ) in patients with moderate to severe plaque psoriasis.

Methods: Data were pooled from 5 trials: BE SURE/BE VIVID/BE READY, their open-label extension (OLE) BE BRIGHT (4-yr data; cut-off 14Nov2022), and BE RADIANT (3-yr data; cut-off 6May2022).^1-5 Patients received BKZ 320mg every 4 weeks (wks)(Q4W) or Q8W; all received Q8W from Wk64 (BE RADIANT)/OLE Wk48 (BE BRIGHT) or next scheduled visit. Treatment-emergent adverse events (TEAEs) are presented as exposure-adjusted incidence rates (EAIRs)/100 patient-yrs (PY) for all patients who received ≥1 BKZ dose, and evaluated separately for Yr1/Yr2/Yr3/Yr4 (Wks0-52/52-104/104-156/156-208) of treatment.

Results: Total BKZ exposure was 6,324.3PY (N=2,186) (Yr1: 2,053.3PY [n=2,186]; Yr2: 1,904.3PY [n=2,013]; Yr3: 1,521.1PY [n=1,803]; Yr4: 819.5PY [n=1,309]).

Overall, TEAEs occurred at an EAIR of 170.5/100PY (Yr1, Yr2, Yr3, Yr4: 230.9/100PY, 137.7/100PY, 107.1/100PY, 99.9/100PY), serious TEAEs at 5.5/100PY (6.5/100PY, 5.9/100PY, 5.8/100PY; 5.6/100PY), and TEAEs leading to discontinuation at 2.9/100PY (4.6/100PY, 2.3/100PY, 2.3/100PY, 1.1/100PY). The most common TEAEs were nasopharyngitis at 12.7/100PY (25.8/100PY, 13.2/100PY, 5.4/100PY, 5.9/100PY), oral candidiasis at 8.9/100PY (18.9/100PY, 10.7/100PY, 6.8/100PY, 5.4/100PY), and upper respiratory tract infection at 5.7/100PY (10.4/100PY, 5.7/100PY, 3.7/100PY, 3.9/100PY).

Throughout, fewer TEAEs occurred with BKZ Q8W vs Q4W (115.4/100PY vs 224.4/100PY), including for oral candidiasis (6.5/100PY vs 16.7/100PY).

Conclusions: BKZ demonstrated good tolerability and a consistent safety profile over 4 yrs in patients with plaque psoriasis. EAIRs of TEAEs remained consistent/decreased with longer BKZ exposure; no new safety findings were identified.

References:

Warren RB et al. N Engl J Med 2021;385:130–41, NCT03412747;
Reich K et al. Lancet 2021;397:487–98, NCT03370133;
Gordon KB et al. Lancet 2021;397:475–86, NCT03410992;
Gordon KB et al. JAMA Dermatol 2022;158:735–44, NCT03598790;
Reich K et al. N Engl J Med 2021;385:142–52, NCT03536884.

Funding: These studies were funded by UCB Pharma. Medical writing support was provided by Costello Medical.

Author Disclosures:

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

DT: Investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oreal, New Bridge, Novartis, Pfizer, Regeneron, Samsung, Sanofi, Target-RWE, UCB Pharma, and Vichy; received grants from AbbVie, LEO Pharma, and Novartis.

MG: Investigator, speaker, consultant or advisory board member for AbbVie, Akros, Amgen, AnaptysBio, Arcutis, Aristea, Aslan, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, MedImmune, Meiji Seika Pharma, Merck, Moonlake Immunotherapeutics, Nimbus, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, Tarsus, UCB Pharma, Union, and Ventyx.

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

BS: Consultant (honoraria) for AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas, Dermavant, Eli Lilly and Company, Imagenebio, Janssen, Kangpu Pharmaceuticals, LEO Pharma, Maruho, Meiji Seika Pharma, Monte Carlo, Novartis, Pfizer, Protagonist, Rapt, Regeneron, Sanofi Genzyme, SG Cowen, Sun Pharma, Takeda, UCB Pharma, Union Therapeutics, Ventyx, and vTv Therapeutics. Stock options from Connect Biopharma and Mindera Health. Speaker for AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, and Sanofi Genzyme. Scientific co-director (consulting fee) for CorEvitas (formerly Corrona) Psoriasis Registry. Investigator for CorEvitas Psoriasis Registry. Editor-in-chief (honorarium) for Journal of Psoriasis and Psoriatic Arthritis.

LP, DD, JMLP: Employee and shareholder of UCB Pharma.

PG: Consultant for AbbVie, Abiogen, Almirall, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, Merck Sharp & Dohme, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB Pharma.

Low Occurrence of Predefined Safety Events Across Six Randomized Clinical Trials of Spesolimab in Dermatologic Conditions

Kenneth B. Gordon¹, Kilian Eyerich², Milan J. Anadkat³, Siew Eng Choon⁴, Boni Elewski⁵, Jonathan N. Barker⁶, Arash Mostaghimi⁷, Ming Tang⁸, Thomas Haeufel⁹, Christian Thoma⁹, Diamant Thaçi¹⁰; ¹Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA, ²Department of Dermatology and Venerology, Medical Center, University of Freiburg, Germany, ³Washington University School of Medicine, Division of Dermatology, St. Louis, MO, USA, ⁴Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Clinical School Johor Bahru, Monash University Malaysia, Subang Jaya, Malaysia, ⁵University of Alabama, Birmingham, AL, USA, ⁶St John’s Institute of Dermatology, Faculty of Life Sciences and Medicine, King’s College London, London, UK, ⁷Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, ⁸Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, China, ⁹Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, ¹⁰Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany

Introduction: In the randomized, placebo-controlled Effisayil 2 trial, the anti-interleukin (IL)-36 receptor antibody spesolimab demonstrated a reassuring safety profile when given over 48 weeks for flare prevention in patients with generalized pustular psoriasis (GPP). Nevertheless, given its novel mechanistic approach, it is important to characterize events relating to IL-36 inhibition with spesolimab as well as those of potential relevance to an intravenously/subcutaneously administered biologic.

Methods: In this analysis, rates of such predefined events – severe/serious/opportunistic infections, potential hypersensitivity reactions, peripheral neuropathies, and malignant tumors – were examined using available data from six randomized trials of spesolimab across various dermatologic conditions.

Results: Events reported in patients receiving spesolimab at various doses and schedules in two trials in GPP, two in palmoplantar pustulosis (PPP), one in atopic dermatitis (AD), and one in hidradenitis suppurativa (HS) were included (total n=345 for spesolimab and 145 for placebo). Exposure to spesolimab was: GPP, 244.3; PPP, 327.8; AD, 40.0; and HS, 45.7 patient-years, respectively. Rates of severe/serious/opportunistic infections were low with spesolimab (3.2% in one GPP trial; otherwise, 0% vs. 0% with placebo), and the incidences of hypersensitivity reactions were similar for spesolimab (7.7–33.3%) and placebo (5.6–44.4%) across trials. There was one report of peripheral neuropathy with spesolimab in a PPP trial (incidence 0–0.9% across trials) versus two (one GPP, one PPP) with placebo (0–3.3%), and one malignancy with spesolimab in GPP (0–1.1% across trials) versus one with placebo in PPP (0–2.3%).

Conclusion: These results support the favorable safety profile of spesolimab seen in Effisayil 2.

Spesolimab Rapidly Improves Quality of Life in Patients with Generalized Pustular Psoriasis, as Per Dermatology Life Quality Index Scores: Data from the Effisayil 2 Trial

Alice B. Gottlieb¹, Bruce Strober², Georgios Kokolakis³, Joseph F. Merola⁴, Min Zheng⁵, Richard Langley⁶, Ming Tang⁷, Patrick Hofmann⁸, Christian Thoma⁸, Richard B. Warren⁹; ¹Icahn School of Medicine at Mount Sinai, New York, NY, USA, ²Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA, ³Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, and Psoriasis Research and Treatment Centre, and Department of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁴Department of Dermatology and Medicine, Division of Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, ⁵Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, ⁶Dalhousie University, Halifax, NS, Canada, ⁷Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, China, ⁸Boehringer Ingelheim International GmbH, Ingelheim, Germany, ⁹Dermatology Centre, Salford Royal NHS Foundation Trust, and National Institute for Health and Care Research Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK

Introduction: Generalized pustular psoriasis (GPP) is a chronic and potentially life-threatening disease characterized by flares of widespread skin pustulation. In Effisayil 2 (NCT04399837), high-dose spesolimab was superior to placebo in GPP flare prevention and numerically reduced the risk of Dermatology Life Quality Index (DLQI) worsening (≥4-point increase in total score from baseline; secondary endpoint), up to Week 48.

Methods: Here, we further analyze the effect of high-dose spesolimab versus placebo on DLQI in Effisayil 2.

Results: Baseline characteristics were generally similar in the high-dose spesolimab (600mg loading dose then 300mg every 4 weeks [N=30]) and placebo groups (N=31) in terms of sex, age, length of disease, and historical flare frequency, although the high-dose spesolimab group had a higher mean±SD DLQI score (11.1±6.9 [missing=1]) versus placebo (7.2±5.6 [missing=0]). At Week 4 in exploratory analysis, more patients in the high-dose spesolimab group (N=29) had no GPP flare and ≥4-point improvement in their DLQI score versus placebo (N=31) (n/N [%]: 10/29 [34.5%] [missing=1] versus 3/31 [9.7%] [missing=0]) at Week 4; this was also seen at Week 48 (11/29 [37.9%] [missing=6] versus 8/31 [25.8%] [missing=0], respectively). Furthermore, a higher proportion of patients treated with spesolimab had no GPP flare and reached a DLQI score of 0 or 1 at all visits up to Week 48 versus placebo (7/29 [24.1%] versus 1/31 [3.2%], respectively).

Conclusion: Adding to previous data from Effisayil 2, this analysis demonstrates that patients treated with spesolimab (including high-dose) rapidly gained improvements in DLQI scores versus placebo, which were sustained through to Week 48.

Efficacy and Safety of Lebrikizumab is Maintained to Two Years in Patients with Moderate-to-Severe Atopic Dermatitis

Emma Guttman-Yassky¹, Stephan Weidinger², Eric Simpson³, Melinda Gooderham⁴, Alan Irvine⁵, Lynda Spelman⁶, Jonathan Silverberg⁷, Hany Elmaraghy⁸, Louise DeLuca-Carter⁸, Maria Lucia Buziqui Piruzeli⁸, Chaoran Hu⁸, Fan Emily Yang⁸, Evangeline Pierce⁸, Laia Bardolet⁹, Diamant Thaci¹⁰; ¹Icahn School of Medicine at Mount Sinai, New York, NY, USA, ²University Hospital Schleswig-Holstein, Kiel, Germany, ³Oregon Health & Science University, Portland, USA, ⁴SKiN for Dermatology, Probity Medical Research and Queen’s University, Peterborough, Ontario, Canada, ⁵Children’s Health Ireland, Dublin, Ireland, ⁶Veracity Clinical Research, Queensland, Australia, ⁷George Washington University School of Medicine and Health Sciences, Washington, DC, USA, ⁸Eli Lilly and Company, Indianapolis, IN, USA, ⁹Almirall S.A, Barcelona, Spain, ¹⁰Institute and Comprehensive Center for Inflammatory Medicine at the University of Lübeck, Lübeck, Germany

Introduction: We report the efficacy and safety of lebrikizumab (LEB) in the long-term extension study ADjoin following 104 Weeks (W) of continuous LEB treatment with and without TCS use.

Methods: Patients in ADvocate1&2 who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were re-randomized 2:2:1 to LEB250mg Q2W, LEB250mg Q4W, or placebo (LEB withdrawal). Patients who completed W52 of ADvocate1&2 were able to enroll in ADjoin. Patients in ADhere who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were able to enroll into ADjoin and randomized 2:1 to LEB250mg Q2W or LEB250mg Q4W. Data are reported for patients originating from ADvocate1&2 and ADhere who received LEB250mg Q2W or Q4W in ADjoin. Efficacy outcomes were assessed based on all collected data (as observed analysis) up to 104W of LEB treatment. Safety was reported from ADjoin enrollment up to the data cut-off April 14, 2023.

Results: At W104, IGA 0/1 was maintained by 38/44 (86.4%; Q2W) and 42/55 (76.4%; Q4W) patients from ADvocate1&2 and 26/31 (83.9%; Q2W) and 11/14 (78.6%; Q4W) patients from ADhere. EASI 75 was maintained by 65/68 (95.6%; Q2W) and 77/80 (96.3% Q4W) ADvocate1&2 patients and 39/41 (95.1%; Q2W) and 24/25 (96.0%; Q4W) ADhere patients at W104. In patients who achieved EASI 75 at W16, EASI 90 was achieved by 56/68 (82.4%; Q2W) and 66/80 (82.5%; Q4W) ADvocate1&2 patients and 35/41 (85.4%; Q2W) and 18/25 (72.0%; Q4W) ADhere patients at 104W.

During ADjoin, 166 of 267 (62.2%) patients from the subpopulations of ADvocate1&2 and ADhere who received LEB Q2W or Q4W in ADjoin reported adverse events (AEs), most of which were mild (31.5%, n=84) or moderate (27.0%, n=72) in severity. Serious AEs were reported by 10 (3.8%) patients. There was one death in the ADhere Q2W arm. Six (2.3%) patients reported AEs leading to treatment discontinuation. The safety profile of LEB in ADjoin is consistent with that observed during ADvocate1&2 and ADhere.

Conclusion: Efficacy outcomes were maintained long-term, over 2 years of continuous LEB treatment, in both LEB250mg Q2W and Q4W arms. The safety profile of LEB in ADjoin is consistent with previous LEB studies in patients with moderate-to-severe AD.

Disclosure: Presented at Fall CDC 2023, Las Vegas.

Expected Spesolimab Plasma Exposure Following Intravenous and Subcutaneous Dosing in Patients with Generalized Pustular Psoriasis

Jason E. Hawkes¹, Jason Guercio², Sree Kurup², Xiujiang Li², Mark Lebwohl³; ¹Integrative Skin Science and Research, Pacific Skin Institute, Sacramento, CA, USA, ²Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, ³Icahn School of Medicine at Mount Sinai, New York, NY, USA

Introduction: Generalized pustular psoriasis (GPP) is a chronic, potentially life-threatening inflammatory skin disease characterized by widespread flares of sterile pustules. Spesolimab is a first-in-class anti-interleukin-36 receptor monoclonal antibody approved to treat GPP flares in adults via intravenous (IV) infusion. The aim of this study was to simulate the plasma pharmaco*kinetics (PK) of IV versus subcutaneous (SC) doses of spesolimab to compare drug exposure profiles and support dosing strategies in patients with GPP.

Methods: A population PK model was developed using individual-level PK, anti-drug antibody, and covariate data from eighteen studies in which subjects were treated with IV or SC spesolimab.¹ The resulting PK model was used to simulate concentration-time profiles following varying doses of IV and SC spesolimab. Peak plasma concentration (C_max), time to peak plasma concentration (T_max), and area under the curve (AUC) were summarized for each dose regimen.

Results: Simulated spesolimab exposures demonstrated that the C_max and AUC of the single dose 900mg IV infusion consistently exceeded that of various single doses of SC spesolimab tested. A SC dose greater than two-fold higher would be required to attain a C_max comparable to that of spesolimab 900mg IV. The difference in exposure between the two administration routes was most pronounced in the first 2 weeks after administration. Slow absorption is expected with SC injection, with T_max attained at later time points after SC dosing compared to immediately following the 90-minute infusion for IV dosing. Results were the same when simulating a two-dose regimen administered one week apart.

Conclusions: PK simulations suggest that treatment with IV and SC spesolimab can result in differences in drug exposure in clinical practice. The immediate and high exposure of IV spesolimab compared with the lower exposure of SC spesolimab are supportive of IV dosing with spesolimab in acute GPP flare treatment vs SC dosing.

Reference:

Boehringer Ingelheim. Data on File: Modeling and simulation report: population pharmaco*kinetics and exposure-response of spesolimab in Generalized Pustular Psoriasis. 2023; c41839684-01

Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

Alexa Hetzel¹, Kristen Teixeira¹, Lenka Hurton², Christine Bailey², Olga Zolochevska², Matthew Goldberg², Ann Quick², ¹Schweiger Dermatology Group, East Windsor, NJ, ²Castle Biosciences, Inc, Friendswood, TX.

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and improve treatment plans. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique. However, this technique has not been used to assess differences in gene expression profiles of MF samples.

Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies.

Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered significantly differentially expressed if there was a |log₂fold change| >1.0 and p_adj <0.05.

Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and super-responders to IL-23 inhibitors including risankizumab relative to those who did not achieve ≥90% improvement.

Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.

Bimekizumab Response Maintenance to 48 weeks in Patients with Moderate to Severe Hidradenitis Suppurativa: Pooled Responder Analysis from the Phase 3, Double-blind, Placebo-controlled, Randomized Clinical Trials BE HEARD I and II

Ingram J.R.^1,11, Porter M.², Chovatiya R.³, Giamarellos-Bourboulis E.J.^4,11, Bechara F.G.⁵, Fujita H.⁶, Gulliver W.⁷, Muller E.⁸, Bari M.⁸, Rolleri R.⁹, Byerly R.⁹, Kirby J.S.¹⁰; ¹Department of Dermatology & Academic Wound Healing, Division of Infection and Immunity, Cardiff University, Cardiff, UK, ²Beth Israel Deaconess Medical Center, Department of Dermatology, Harvard Medical School, Boston, USA, ³Northwestern University Feinberg School of Medicine, Chicago, USA, ⁴4^thDepartment of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, ⁵Department of Dermatology, Venerology and Allergology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany, ⁶Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan, ⁷Newlab Clinical Research Inc, St John’s, Newfoundland, Canada, ⁸UCB Pharma, Slough, UK, ⁹UCB Pharma, Morrisville, USA, ¹⁰Department of Dermatology, Penn State University, Hershey, USA, ¹¹European Hidradenitis Suppurativa Foundation, Dessau, Germany.

Introduction: Hidradenitis suppurativa (HS) is a chronic and painful inflammatory skin disease associated with significant comorbidities and poor quality of life,¹ thus it is important that treatment efficacy and clinical responses are maintained over time. Bimekizumab (BKZ), a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F and IL-17A, has previously demonstrated efficacy in patients with moderate to severe HS at phase 2.² Here we present data from the phase 3 BE HEARD I and II studies, reporting maintenance of response through Week (Wk) 48 in adult patients with moderate to severe HS.^3,4

Procedure: Data from the randomized, double-blind, placebo (PBO)-controlled, multicenter trials were pooled. The trials included an initial (Wks 0–16) and a maintenance treatment period (Wks 16–48). Adult patients were randomized 2:2:2:1 (initial/maintenance) to receive BKZ 320mg every 2 wks (Q2W)/Q2W, BKZ Q2W/every 4 wks (Q4W), BKZ Q4W/Q4W, or PBO/BKZ Q2W. Maintenance of response is reported as the percentage of BKZ-treated patients who achieved 50% HS Clinical Response (HiSCR₅₀), or an abscess and inflammatory nodule (AN) count of 0, 1, or 2, at Wk16 and maintained response through Wk48. Data are reported for Wk16 responders through Wk48 from the groups randomized to receive any BKZ dosing regimen from baseline (Wk0).

Results: At baseline, 1,014 patients were randomized to PBO/BKZ Q2W (n=146), BKZ Q4W/Q4W (n=288), BKZ Q2W/Q4W (n=292), or BKZ Q2W/Q2W (n=288). Among Wk16 HiSCR₅₀ responders in the BKZ Q4W/Q4W (n=152), BKZ Q2W/Q4W (n=155), and BKZ Q2W/Q2W (n=160) groups, 89.6% (103/115), 88.5% (116/131), and 88.8% (111/125) maintained response through Wk48, respectively. Among patients with an AN count of 0, 1, or 2 at Wk16 in the BKZ Q4W/Q4W (n=87), BKZ Q2W/Q4W (n=99), and BKZ Q2W/Q2W (n=104) groups, 86.4% (57/66), 88.0% (73/83), and 82.1% (69/84) maintained response through Wk48, respectively.

Conclusion: Almost all patients who responded after an initial 16 wks of BKZ treatment maintained HiSCR₅₀ and AN count of 0, 1, or 2 clinical response rates through Wk48. Maintenance of response was observed across patients who received BKZ from baseline.

References:

Dufour DN. Postgrad Med J 2014;90:216–21
Glatt S. JAMA Dermatol 2021;157:1279–88
BE HEARD I: https://clinicaltrials.gov/ct2/show/NCT04242446
BE HEARD II: https://clinicaltrials.gov/ct2/show/NCT04242498.

Funding: UCB Pharma. Medical writing support was provided by Costello Medical.

Author Disclosures:

JRI: Receives a stipend as Editor‑in‑Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate; consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake Immunotherapeutics, Novartis, UCB Pharma, and Union Therapeutics; served on advisory boards for Insmed, Kymera Therapeutics and Viela Bio; co‑copyright holder of HiSQOL^© and HS-IGA; department receives income from copyright of the Dermatology Life Quality Instrument (DLQI) and related instruments.

MP: Consultant and investigator for AbbVie, Anaptys Bio, Aristea, Eli Lilly and Company, Incyte, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Prometheus, Sanofi, Sonomabio, and UCB Pharma; consultant for Alumis, FIDE, and Trifecta Clinical; investigator for Bayer, Bristol Myers Squibb, and OASIS Pharmaceuticals; received royalties from Beth Israel Deaconess Medical Center.

RC: Served as an advisory board member, consultant, and/or investigator for AbbVie, Apogee, Arcutis, Argenx, Aslan, Beiersdorf, Bristol Myers Squibb, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly and Company, Galderma, Genentech, Incyte, L’Oréal, LEO Pharma, Novan, Pfizer, Regeneron, Sanofi, and UCB Pharma; speaker for AbbVie, Arcutis, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Incyte, LEO Pharma, Novan, Pfizer, Regeneron, Sanofi, and UCB Pharma.

EJGB: Received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi, and XBiotech; independent educational grants from Abbott CH, AxisShield, bioMérieux, InflaRx GmbH, Johnson & Johnson, MSD, Novartis, Sobi, and XBiotech; funding from the Horizon2020 Marie Skłodowska-Curie International Training Network “the European Sepsis Academy” (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis), and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

FGB: Received honoraria for consulting and/or presentations and/or sponsoring for scientific projects and/or clinical studies from AbbVie, AbbVie Deutschland, Beiersdorf, Boehringer Ingelheim, Dr. Wolff, Incyte, Janssen-Cilag, Mölnlycke, MoonLake Immunotherapeutics, Novartis, and UCB Pharma

HF: Received honoraria or fees for serving on advisory boards, as a speaker and as a consultant, as well as grants as an investigator from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen, Japan Blood Products Organization, JMEC, Kaken Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nihon Pharmaceutical, Novartis, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Pharma, and Ushio.

WG: Grants and research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer. Honoraria for advisory boards/invited talks/consultation: AbbVie, Actelion, Amgen, Arylide, Bausch Health, Boehringer, Celgene, Cipher, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, Sun Pharma, Tribute, UCB Pharma, and Valeant. Clinical trials (study fees): AbbVie, Asana Biosciences, Astellas, Boerhinger Ingleheim, Celgene, Corrona/National Psoriasis Foundation, Devonian, Eli Lilly, Galapagos, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma.

EM, RR, RB: Employee and shareholder of UCB Pharma.

MB: Employee of UCB Pharma.

JSK: Reports personal fees from AbbVie, ChemoCentryx, CSL Behring, DermTech, Incyte, Insmed, Janssen, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; personal fees and grants from Incyte; co-copyright holder of HiSQOL^©; consultant for and received honoraria from AbbVie, Alumis, DermTech, Incyte, Insmed, Janssen, Moonlake Immunotherapeutics, Novartis, and UCB Pharma; has been a speaker for AbbVie, Janssen, Novartis, and UCB Pharma.

Dupilumab is Efficacious in Patients with Prurigo Nodularis Regardless of History of Atopic Comorbidities: Pooled Results From Two Phase 3 Trials (LIBERTY-PN PRIME and PRIME2)

Brian S. Kim¹, Margarida Gonçalo², Tsukasa Ugajin³, Amy Praestgaard⁴, Melanie Makhija⁴, Joseph Zahn⁵, Ashish Bansal⁵, Simmi Wiggins⁶; ¹Icahn School of Medicine at Mount Sinai, New York, NY, USA, ²Department of Dermatology, University of Coimbra, Coimbra, Portugal, ³Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan, ⁴Sanofi, Cambridge, MA, USA, ⁵Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, ⁶Sanofi, Reading, UK

Introduction: Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules. Nearly half of affected adult patients have a history of atopic comorbidity, such as atopic dermatitis (AD). The purpose of this study is to report the efficacy of dupilumab in patients with PN with or without history of atopic comorbidities, in a pre-specified analysis of pooled data from two phase 3 trials.

Methods: In the randomized, double-blind, placebo-controlled, 24-week studies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), adults with PN inadequately controlled by topical prescription therapies were randomized 1:1 to dupilumab 300mg every 2 weeks or matched placebo. Atopic patients were defined as patients with a physician-documented history, or current diagnosis, of at least one of the following atopic comorbidities: AD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy. Efficacy was assessed from baseline to Week 24 using the Worst Itch Numerical Rating Scale (WI-NRS; 0–10) and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; 0–4).

Results: 311 patients were randomized (dupilumab n=153, atopic/non-atopic N=67/86; placebo n=158, atopic/non-atopic N=68/90). At Week 24, significantly more atopic and non-atopic dupilumab-treated patients achieved a ≥4-point improvement in WI-NRS (58.2%/59.3%), and an IGA PN-S score of 0 or 1 (52.2%/41.9%) vs placebo (20.6%/17.8% [nominal P<0.0001/P<0.0001] and 16.2%/17.8% [nominal P<0.0001/P=0.0005], respectively). The proportion of patients achieving concomitant ≥4-point improvement in WI-NRS and IGA PN-S score of 0 or 1 was higher for both dupilumab-treated atopic and non-atopic patients (37.3%/33.7%) vs placebo (7.4%/10.0% [nominal P=0.0057/P<0.007]). Overall safety was consistent with the known dupilumab safety profile, with no remarkable differences between atopic and non-atopic patients.

Conclusion: Dupilumab treatment improves itch and skin lesions in patients with both atopic and non-atopic PN, indicating that underlying type 2 inflammation is present in patients with PN regardless of their history of atopic comorbidities.

Acknowledgments: Data included in this abstract were originally presented at the 25th World Congress of Dermatology (WCD 2023); July 3-8; Singapore. Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT04183335 and NCT04202679. Authors thank Sona Budhiraja for presenting the abstract on behalf of authors at the Diversity in Dermatology (DiD) 2024 meeting. Medical writing assistance was provided by Benjamin Danet, PhD, and Maria Coimbra-Dores, PhD, of Excerpta Medica, and editorial assistance for this abstract was provided by Teresa Antony, Sanofi and was funded by Sanofi and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline.

Disclosures: Kim BS: AbbVie, Almirall, Amagma, Argenx, AstraZeneca, Bellus Health, Blueprint Medicines, Boehringer Ingelheim, BMS, Cara Therapeutics, Daewoong Pharmaceutical, Eli Lilly, Genzyme, GSK, Guidepoint Global, Incyte, Janssen, LectureLinx, LEO Pharma, OM Pharma, Pfizer, RecensMedical, Regeneron Pharmaceuticals Inc., Shaperon, Trevi Therapeutics, WebMD – consultant; Locus Biosciences – may hold stock and/or stock options in the company. Gonçalo M: AbbVie, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, Takeda − advisory board member and/or speaker. Ugajin T: AbbVie, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Takeda – lectures. Praestgaard A, Makhija M, Wiggins S: Sanofi − employees, may hold stock and/or stock options in the company. Zahn J, Bansal A: Regeneron Pharmaceuticals Inc. − employees and shareholders.

Efficacy and Safety of the Oral Bruton’s Tyrosine Kinase Inhibitor, Remibrutinib, in Patients with Moderate-to-Severe Hidradenitis Suppurativa in a Randomized, Phase 2, Double-blind, Placebo-controlled Platform Study

Alexa B Kimball¹, Errol P Prens², Falk G Bechara³, Bo Bang⁴, Tirtha Sengupta⁵, Christian Loesche⁴; ¹Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, ²Department of Dermatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, ³Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany, ⁴Novartis Pharma AG, Basel, Switzerland, ⁵Novartis Healthcare Ltd., Hyderabad, India.

Introduction: A possible role for B cells and activation of the Bruton’s tyrosine kinase (BTK) pathway in the pathogenesis of hidradenitis suppurativa (HS) has recently emerged.^1,2

Study overview: NCT03827798 is a randomized, double-blind, placebo-controlled platform study assessing different investigational drugs in patients with moderate-to-severe HS. In one study cohort, patients were randomized to receive remibrutinib (highly selective oral BTK inhibitor) 25mg (N=33), 100mg (N=33), or placebo (N=11), twice daily for 16 weeks. The primary endpoint was the simplified HiSCR rate (sHiSCR; ≥50% reduction in abscess and inflammatory nodule [AN] count, with no increase in draining tunnels, versus baseline) and key exploratory endpoints were HiSCR, HiSCR75, and HiSCR90 rates in patients treated with remibrutinib versus pooled placebo from all study cohorts (N=49) at week 16. The primary endpoint was assessed using Bayesian analysis (probability that remibrutinib treatment is better than placebo).

Results: Patients treated with remibrutinib reported greater sHiSCR at week 16 (remibrutinib 25mg, 72.7% [probability=0.999]; 100mg, 48.5% [probability=0.896]) versus placebo (34.7%), with separation between remibrutinib and placebo observed from week 2. Responder rates at week 16 were higher in remibrutinib 25mg and 100mg treatment arms versus placebo (HiSCR: 69.7%, 48.5%, versus 32.7%; HiSCR75: 42.4%, 27.3% versus 18.4%; HiSCR90: 36.4%, 15.2% versus 8.2%). Remibrutinib was well tolerated; adverse event (AE) frequencies were comparable between treatment arms, with three serious AEs reported (N=1 per arm).

Conclusion: Remibrutinib showed superior clinical efficacy versus placebo in patients with moderate-to-severe HS. BTK inhibition may emerge as a promising therapeutic intervention in HS.

References:

Gudjonsson JE, et al. JCI Insight. 2020;5.
Frew JW, et al. Exp Dermatol 2020; 29: 509–515.

Pooled Safety Assessments from the Multinational Phase 3 THRIVE-AA1 and THRIVE-AA2 Trials of Deuruxolitinib in Adult Patients with Moderate-to-severe Alopecia Areata

Brett King¹, Maryanne Makredes Senna², Natasha A. Mesinkovska³, Arash Mostaghimi⁴, Colleen Hamilton⁵, James Cassella⁵; ¹Department of Dermatology, Yale School of Medicine, New Haven, CT, US, ²Lahey Hair Loss Center of Excellence, Lahey Hospital and Medical Center, Burlington, MA, US, ³Department of Dermatology, University of California, Irvine, CA, US, ⁴Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, US, ⁵Sun Pharmaceutical Industries, Inc., Lexington, MA, US

Introduction: Deuruxolitinib, a selective JAK1/JAK2 inhibitor, demonstrated significant hair regrowth in patients with alopecia areata (AA) in the THRIVE-AA1 and THRIVE-AA2 Phase 3 trials. Pooled safety measures from these 2 trials are reported.

Methods: Eligible patients with AA 18–65 years of age with ≥50% scalp hair loss and current AA episode >6 months and <10 years were treated with placebo, deuruxolitinib 8mg BID, or 12mg BID for 24 weeks. Safety assessments included adverse events (AEs), vital signs, electrocardiograms and clinical labs.

Results: 1220 patients were randomized to placebo (n=270), deuruxolitinib 8mg twice daily (BID; n=606), or deuruxolitinib 12mg BID (n=344). The most common AEs (≥5% in any group) were COVID-19, headache, acne, nasopharyngitis, asymptomatic COVID-19, and increased creatine phosphokinase. Treatment-emergent serious AEs (SAEs) occurred in 14 patients (including appendicitis, COVID-19, chest pain, ileus, epilepsy, spontaneous abortion, adjustment disorder, dyspnea, radius fracture, osteoarthritis, and migraine with aura), of which 3 SAEs considered related to deuruxolitinib occurred in 2 patients (meningitis, pyrexia and influenzal pneumonia). Of the 110 patients who did not complete the study, 31 (28.2%) discontinued due to AEs, comprising 4 (18.2%), 18 (31.0%), and 9 (30.0%) from the placebo, 8mg BID, and 12mg BID groups, respectively. Incidence and severity of AEs were similar for the deuruxolitinib 8mg BID and 12mg BID groups.

Conclusion: Both doses of deuruxolitinib were generally well tolerated, and the overall safety profile in patients with alopecia areata indicates suitability for clinical use.

Sponsorship: The study and medical writing support were funded by Sun Pharma.

Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne: Comparison of 4 Clinical Trials

Leon H. Kircik, MD^1-3, Zoe D. Draelos, MD⁴, Michael Gold, MD⁵, Neil Sadick, MD^6,7, Neal Bhatia, MD⁸; ¹Icahn School of Medicine at Mount Sinai, New York, NY, ²Indiana University School of Medicine, Indianapolis, IN, ³Physicians Skin Care, PLLC, DermResearch, PLLC, and Skin Sciences, PLLC, Louisville, KY, ⁴Dermatology Consulting Services, PLLC, High Point, NC, ⁵Tennessee Clinical Research Center, Nashville, TN, ⁶Weill Cornell Medical College, New York, NY, ⁷Sadick Dermatology, New York, NY, ⁸Therapeutics Clinical Research, San Diego, CA

Introduction: Combination therapies targeting multiple processes of acne pathogenesis are recommended for most acne patients. A three-pronged approach using an antibiotic, retinoid, and antibacterial may also increase treatment efficacy versus monotherapy or dual-combination products. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (BPO) polymeric mesh gel (CAB) is the first fixed-dose, triple-combination topical approved by the FDA for the treatment of acne. The objective of this analysis was to compare treatment success and effect size of once-daily CAB with its three constituent dyad gels, branded adapalene 0.3%/BPO 2.5% gel, and vehicle across four clinical studies.

Methods: Two phase 2 (NCT03170388, NCT04892706) and two phase 3 (NCT04214652, NCT04214639) double-blind, randomized, 12-week studies enrolled participants with moderate-to-severe acne. In all studies, treatment success at week 12 (defined as a ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) was a co-primary endpoint. Other co-primary endpoints (reduction from baseline in inflammatory and noninflammatory lesions) are not shown here. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. A post hoc analysis of number needed to treat (NNT)—the number of patients who need to be treated with an intervention for one additional patient to achieve success versus vehicle—was performed to provide an additional measure of treatment effect and to indirectly compare data across studies.

Results: Across studies, approximately half of CAB-treated participants achieved treatment success by week 12 (range: 49.6-52.5%) versus less than one-fourth with vehicle (range: 8.1%-24.9%; P<0.01, all) and less than one-third with component dyads or branded adapalene 0.3%/BPO 2.5% (range: 27.8%-32.9%; P≤0.001, all). Treatment success rates were significantly greater for all active treatments versus vehicle (P<0.01, all). NNT values for CAB (3-5) were lower (better) than for constituent dyads (5-6) or branded adapalene 0.3%/BPO 2.5% (7), further indicative of greater efficacy. TEAEs with CAB were mostly of mild-to-moderate severity. TEAE and discontinuation rates were similar or lower with CAB gel than with adapalene/BPO dyad gels. Mean cutaneous safety/tolerability scores with CAB gel were <1 (mild) at all timepoints.

Conclusions: CAB gel demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels and branded adapalene 0.3%/BPO 2.5% gel, with approximately half of participants achieving clear/almost clear skin by 12 weeks with CAB. Due to acne pathogenesis, a triple-combination treatment may result in clinical success more often than two-ingredient combination products.

Funding: Ortho Dermatologics.

Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Neil J. Korman¹, Thierry Passeron², Yukari Okubo³, Jerry Bagel⁴, Richard B. Warren^5,6, Lynda Spelman⁷, Kevin Winthrop⁸, Renata M. Kisa⁹, Kim Hoyt⁹, Thomas Scharnitz⁹, Subhashis Banerjee⁹, Diamant Thaçi¹⁰, Mona Shahriari¹¹, Linda Stein Gold¹²; ¹Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA, ²Université Côte d’Azur, University Hospital of Nice, Nice, France, ³Tokyo Medical University, Tokyo, Japan, ⁴Psoriasis Treatment Center of New Jersey, East Windsor, NJ, USA, ⁵Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK, ⁶NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, ⁷Veracity Clinical Research, Brisbane, QLD, Australia, ⁸Oregon Health & Science University, Portland, OR, USA, ⁹Bristol Myers Squibb, Princeton, NJ, USA, ¹⁰University of Lübeck, Lübeck, Germany, ¹¹Yale University School of Medicine, New Haven, and Central Connecticut Dermatology, Cromwell, CT, USA, ¹²Henry Ford Health System, West Bloomfield, MI, USA

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE; NCT04036435) trial and receive open-label deucravacitinib. Changes in laboratory parameters in the blood known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment.

Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4y; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed.

Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. A total of 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed.

Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) that have been observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.

Nemolizumab Long-term Efficacy and Safety up to 52 weeks in the OLYMPIA Open-label Extension Study in Patients with Prurigo Nodularis: An Interim Analysis

Shawn G Kwatra, MD¹, Franz J Legat, MD², Adam Reich, MD³, Carle Paul, MD⁴, Dagmar Simon, MD⁵, Luigi Naldi, MD⁶, Gil Yosipovitch, MD⁷, Faiz Ahmad, MD⁸, Zarif Jabbar-Lopez, MD⁹, Christophe Piketty, MD⁹, Sonja Ständer, MD¹⁰; ¹Johns Hopkins Itch Center, Johns Hopkins University School of Medicine, Baltimore, MD, ²Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria, ³Department of Dermatology, University of Rzeszów, Rzeszów, Poland, ⁴Department of Dermatology, Medical University of Toulouse, Toulouse, France, ⁵Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland, ⁶Academic Research Centre, Centro Studi GISED, Bergamo, Italy, ⁷Miami Itch Center, Miller School of Medicine at the University of Miami, Miami, FL, ⁸Galderma Laboratories, Dallas, TX, ⁹Galderma R&D, Zug, Switzerland, ¹⁰Center for Chronic Pruritus, University Hospital Münster, Münster, Germany

Background: Nemolizumab, an interleukin-31 receptor-alpha antagonist, demonstrated efficacy and safety in patients with prurigo nodularis (PN) in OLYMPIA 1&2 phase 3 studies up to 24 weeks.^1,2 This interim analysis evaluated the long-term efficacy and safety of nemolizumab treatment up to 52 weeks from the ongoing long-term extension (LTE) study (OLYMPIA-LTE [NCT04204616]).

Methods: OLYMPIA-LTE is a 184-week (W) open-label study of eligible patients with PN from Phase 2 and phase 3 lead-in studies. All patients received open-label nemolizumab 30mg (<90kg) or 60mg (≥90kg) every 4 weeks. At baseline, patients who had received placebo in lead-in studies (nemolizumab-naïve) received nemolizumab 60mg, whereas patients who received nemolizumab (continuous-nemolizumab) continued receiving the same regimens from the lead-in studies. Efficacy assessments included all observed data through W52: the proportion of patients achieving Investigator’s Global Assessment (IGA) 0/1, ≥4-point improvement from lead-in baseline in Peak-Pruritus NRS and Sleep-Disturbance NRS (PPNRS4 and SDNRS4), PPNRS<2; and mean DLQI.

Results: Based on available data at W52, IGA 0/1 response rates were 69.2% (continuous-nemolizumab) and 64.5% (nemolizumab-naïve), and PPNRS4 response rates were 88.9% (continuous-nemolizumab) and 83.3% (nemolizumab-naïve). Similar trends were observed for SDNRS4 and PPNRS<2. Nemolizumab-naïve patients rapidly achieved responses consistent with the continuous-nemolizumab cohort, as early as W4 for PPNRS4 and PPNRS<2. The mean (±SD) DLQI at W52 was 3.3 (±4.7) (continuous-nemolizumab) and 3.5 (±4.7) (nemolizumab-naïve). No safety signals were observed.

Conclusion: In this interim analysis, nemolizumab treatment up to W52 provided ongoing improvements in nodule resolution, itch, sleep disturbance and quality-of-life in patients with moderate-to-severe PN.

Five-Year US Pharmacovigilance Report on Brodalumab

Mark Lebwohl¹, John Koo², April Armstrong³, Bruce Strober^4,5, George Martin⁶, Nicole Rawnsley⁷, Earl Goehring Jr⁷, Gina Mangin⁸, Abby Jacobson⁷; ¹Icahn School of Medicine at Mount Sinai, New York, NY, ²Psoriasis and Skin Treatment Center, University of California, San Francisco, San Francisco, CA, ³UCLA, Los Angeles, CA, ⁴Central Connecticut Dermatology Research, Cromwell, CT, ⁵Yale University, New Haven, CT, ⁶Dr. George Martin Dermatology Associates, Kihei, HI, ⁷Bausch Health Companies Inc, Bridgewater, NJ, ⁸Sand Lake Dermatology Center, Orlando, FL

Introduction: Brodalumab, a human interleukin-17 receptor A antagonist, is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. The brodalumab US prescribing information carries a boxed warning regarding suicidal ideation and behavior despite no established causal association. Herein, we summarize 5 years of US pharmacovigilance data on brodalumab.

Methods: This analysis summarizes pharmacovigilance data provided to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, to August 14, 2022. The prevalence of common (incidence ≥1%) adverse events (AEs) listed in the brodalumab prescribing information and other AEs of special interest are described.

Results: A total of 4744 patients in the United States were included, representing an estimated exposure of 5815 patient-years. As described in previous pharmacovigilance reports, arthralgia was the most commonly reported AE. During the 5-year period, 11 cases of adjudicated major adverse cardiovascular events were reported, with a crude AE reporting rate of 0.23 events/100 patients. The crude AE reporting rate of serious infections was 2.23 events/100 patients, with no serious fungal infections reported. There were 4 new cases of candida infections since the 4-year report; however, all 4 patients continued brodalumab. Additionally, since the beginning of the pandemic, there were 40 confirmed and 2 suspected cases of coronavirus disease 2019 (COVID-19), with no new deaths due to COVID-19 in year 5. Among 49 reported malignancies affecting 42 patients over 5 years (crude AE reporting rate, 0.89 events/100 patients), 3 were deemed possibly related to brodalumab. One new case of inflammatory bowel disease (ie, irritable bowels) was reported; this patient maintained therapy. One new case of Crohn’s disease was reported; however, the case was considered invalid owing to lack of information despite multiple follow-up attempts with the reporter. No new suicide attempts were reported in year 5, and there were no completed suicides throughout the 5 years.

Conclusion: Five-year pharmacovigilance data are consistent with the established safety profile of brodalumab observed in long-term clinical trials and previous US pharmacovigilance reports, without the emergence of any new safety signals.

Funding: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health Companies Inc.

Previous presentation: Data included in this abstract have been previously presented in full at the Fall Clinical Dermatology Conference; October 19-22, 2023; Las Vegas, NV.

Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion for Hyperkeratotic Plaque Psoriasis

Mark Lebwohl¹, George Han², Zoe Draelos³, Leon Kircik¹, Amber Blair⁴, Abby Jacobson⁵; ¹Icahn School of Medicine at Mount Sinai, New York, NY, ²Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, ³Dermatology Consulting Services, High Point, NC, ⁴Dermatology, Laser & Vein Specialists of the Carolinas, Charlotte, NC, ⁵Ortho Dermatologics (a division of Bausch Health Companies Inc), Bridgewater, NJ

Background: Skin clearance may be difficult to achieve for patients with hyperkeratotic psoriatic plaques (ie, plaques with considerable thickness) who receive topical therapy. This post hoc analysis of two phase 3 trials of HP/TAZ in patients with moderate-to-severe plaque psoriasis (N=418) evaluated efficacy and safety in a subgroup of participants with hyperkeratotic plaques (defined as investigator’s global assessment [IGA] score of 3 with moderate-to-severe elevation or IGA score of 4) at baseline (n=375).

Methods: Participants with hyperkeratotic plaques applied HP/TAZ or vehicle once daily for 8 weeks and were assessed at weeks 2, 4, 6, 8, and 12. Endpoints included treatment success (≥2-grade improvement from baseline in IGA and IGA score of 0 or 1); treatment success of target lesion (≥2-grade improvement from baseline score in erythema, scaling, and plaque elevation); and safety.

Results: Rates of treatment success were significantly greater for those treated with HP/TAZ versus vehicle at all time points (P≤0.001). Rates of elevation, scaling, and erythema treatment success were also significantly greater for those treated with HP/TAZ versus vehicle at all time points (P≤0.003). More participants receiving HP/TAZ versus vehicle reported none-to-minimal elevation as early as week 2 (29.7% vs 10.5%), which was maintained through week 12 (53.4% vs 20.2%). No new safety signals were reported.

Conclusions: These data demonstrate that HP/TAZ is associated with early and prolonged improvement in hyperkeratotic plaques with a specific focus on reduced elevation. Thus, HP/TAZ is a viable option for this difficult-to-treat patient population.

References:

Farci and Mahabal. Hyperkeratosis. StatPearls [Internet]. 2023.
Rakkhit T, Panko JM, Christensen TE, et al. Br J Dermatol. 2009;160(5):1083-1089.
Duobrii [package insert]. Bausch Health Companies Inc; 2020.
Sugarman JL, Weiss J, Tanghetti EA, et al. J Drugs Dermatol. 2018;17(8):855-861.

Financial disclosures: This study was supported by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and was funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health Companies Inc.

Roflumilast Cream 0.3% in Patients with Psoriasis: Improvement in Pruritus and Other Patient Reported Outcomes from Two Pooled Phase 3 Trials (DERMIS-1/DERMIS-2)

Mark Lebwohl¹, Chih-Ho Hong², Leon Kircik³, Jennifer Soung⁴, Melinda Gooderham⁵, Angela Moore⁶, James Del Rosso⁷, Irina Turchin⁸, David Krupa⁹, Robert Higham⁹, David R. Berk⁹; ¹Icahn School of Medicine at Mount Sinai, New York, NY, USA, ²Probity Medical Research and University of British Columbia, Department of Dermatology and Skin Science, Surrey, BC, Canada, ³Icahn School of Medicine at Mount Sinai, New York, New York; Indiana Medical Center, Indianapolis, Physicians Skin Care, PLLC and Skin Sciences, PLLC, Louisville, Kentucky, USA, ⁴Southern California Dermatology, Santa Ana, CA, USA, ⁵SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada, ⁶Arlington Research Center, Arlington, TX, USA and Baylor University Medical Center, Dallas, TX, USA, ⁷JDR Dermatology Research Center, LLC, Las Vegas, Nevada, and Advanced Dermatology and Cosmetic Surgery, Maitland, Florida, USA, ⁸Brunswick Dermatology Center, Fredericton, NB, Canada, ⁹Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA.

Introduction: Roflumilast cream 0.3% is a highly selective, potent phosphodiesterase 4 inhibitor approved for topical treatment of plaque psoriasis, including intertriginous areas, in patients ≥12 years of age. Pooled efficacy, safety, and tolerability from two identical, phase 3 trials conducted in patients aged ≥2 years with plaque psoriasis affecting 2-20% body surface area (DERMIS-1 [NCT04211363] and DERMIS-2 [NCT04211389]) were previously reported. Significantly more roflumilast-treated patients achieved IGA Success (Clear or Almost Clear plus ≥2-grade improvement from baseline; n=576) at week 8 than vehicle-treated patients (39.9% vs. 6.5%; P<0.0001; n=305) with low rates of adverse events, which were similar between treatment groups.

Methods: Here we describe pooled patient-reported outcomes: Worst-Itch-Numeric Rating Scale (WI-NRS; Success: ≥4-point improvement in patients with baseline ≥4), Psoriasis Symptom Diary (PSD), and Dermatology Life Quality Index (DLQI).

Results: Greater improvement in pruritus was observed at Week 8 in roflumilast-treated than vehicle-treated patients (WI-NRS Success: 68.5% vs. 31.3%; WI-NRS score 0/1: 55.4% vs 19.4%; both P<0.0001) with differences observed at the earliest timepoint, Week 2. Greater reduction from baseline in DLQI total score (−4.6 vs. −1.6; P<0.0001) and percent change from baseline in PSD total score occurred in roflumilast-treated patients vs vehicle (−69.2% vs −26.0%; P<0.0001; n=525 and n=277, respectively) at Week 8. Consistent improvement occurred across PSD domains of patient reported signs and symptoms of their psoriasis (severity and bothersomeness) as well as improvement of emotional domains (embarrassment).

Conclusion: Roflumilast cream 0.3% improved psoriasis across multiple patient-reported outcomes including pruritus and quality of life. Sponsored by Arcutis Biotherapeutics, Inc.

Efficacy of the Oral JAK1/JAK2 Inhibitor Deuruxolitinib in Adult Patients with Moderate-to-severe Alopecia Areata: Pooled Results from the Multinational Double-blind, Placebo-controlled THRIVE-AA1 and THRIVE-AA2 Phase 3 Trials

Maryanne Makredes Senna¹, Brett King², Natasha A. Mesinkovska³, Arash Mostaghimi⁴, Colleen Hamilton⁵, James Cassella⁵; ¹Lahey Hair Loss Center of Excellence, Lahey Hospital and Medical Center, Burlington, MA, US, ²Department of Dermatology, Yale School of Medicine, New Haven, CT, US, ³Department of Dermatology, University of California, Irvine, CA, US, ⁴Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, US, ⁵Sun Pharmaceutical Industries, Inc., Lexington, MA, US.

Introduction: Alopecia areata (AA) is a chronic autoimmune disease causing complete or partial loss of hair. Pooled results from two Phase 3 clinical trials of deuruxolitinib in adults with moderate-to-severe AA are reported.

Methods: Eligible patients with AA (18–65y of age) with ≥50% scalp hair loss and current AA episode >6 months and <10 years were treated with placebo, deuruxolitinib 8mg BID, or deuruxolitinib 12mg BID for 24 weeks. Hair loss was measured by the Severity of Alopecia Tool (SALT).

Results: 1209 patients were randomized to placebo (n=267) or deuruxolitinib 8mg twice daily (BID; n=600) or 12mg BID (n=342). Both doses of deuruxolitinib met the primary efficacy endpoint (SALT score ≤20 at Week 24). For 8mg BID and 12mg BID, 31.0% and 40.3% of patients achieved a SALT score ≤20 at Week 24 compared with 0.8% for placebo (P <0.0001). Significant differences from placebo for both doses of deuruxolitinib were seen as early as 8 weeks (P <0.0005). In addition, 22.5% and 31.6% of the 8mg BID and 12mg BID groups, respectively, achieved a SALT score ≤10 at Week 24 compared with 0% of the placebo group (P <0.0001). For relative change in SALT from baseline, all differences for both dose groups vs placebo were significant as early as Week 4 (P <0.01).

Conclusions: Both doses of deuruxolitinib resulted in significant regrowth of scalp hair from 8 weeks, continuing throughout 24 weeks. These results demonstrate the clinically meaningful efficacy of deuruxolitinib for moderate-to-severe AA.

Sponsorship: The study and medical writing support were funded by Sun Pharma.

Dupilumab Reduces Disease Activity in Patients with Chronic Spontaneous Urticaria: LIBERTY-CSU CUPID Study A

Marcus Maurer^1,2, Ana Giménez-Arnau³, Allen Kaplan⁴, Sarbjit Saini⁵, Luis Felipe Ensina^6,7, Michihiro Hide⁸, Amy Praestgaard⁹, Tayler Gonzalez⁹, Sonya Cyr¹⁰, Philip Sugerman⁹; 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, ³Department of Dermatology, Hospital del Mar Research Institute, Universitat Pompeu Fabra, Barcelona, Spain, ⁴Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA, ⁵Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA, ⁶Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil, ⁷CPAlpha Clinical Research Center, Barueri, Brazil, ⁸Department of Dermatology, Hiroshima Citizens Hospital and Department of Dermatology, Hiroshima University, Hiroshima, Japan, ⁹Sanofi, Cambridge, MA, USA, ¹⁰Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

Rationale: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by wheals and/or angioedema that recur for >6 weeks. The overall goal of CSU treatment is to clear the signs and symptoms until urticaria shows spontaneous remission. Many patients with CSU fail to respond adequately to standard-of-care H1-antihistamines (H1-AH).

Methods: LIBERTY-CSU CUPID Study A (NCT04180488) was a randomized, placebo-controlled, 24-week, phase 3 trial that evaluated dupilumab efficacy and safety in patients aged ≥6 years with CSU who remained symptomatic despite H1-A1 treatment and were omalizumab-naïve. Background therapy was study-defined H1-AH at up to 4-fold the approved dose. Endpoints included the proportion of patients with Urticaria Activity Score over 7 days (UAS7) ≤6 and UAS7=0 up to Week 36.

Results: In patients with CSU inadequately controlled with H1-AH, dupilumab treatment resulted in a numerically greater proportion of patients achieving well-controlled urticaria (UAS7≤6) from Week 8 and urticaria-free status (UAS7=0) from Week 14, vs placebo. At Week 24, 53.1% of dupilumab-treated patients achieved UAS7≤6 and 35.9% achieved UAS7=0 (vs 34.0% and 18.9% with placebo; P=0.0379 and P=0.0411, respectively). Following discontinuation of dupilumab at Week 24, the proportion of patients achieving well-controlled urticaria or urticaria-free status (UAS7≤6 and UAS7=0) remained numerically greater for dupilumab vs placebo to Week 36.

Conclusion: A numerically greater proportion of patients treated with dupilumab achieved well-controlled urticaria (UAS≤6) or urticaria-free status (UAS7=0) vs placebo. Dupilumab safety was consistent with the known safety profile.

Acknowledgements and funding sources: Data included in this abstract was originally presented at the AAAAI 2024 congress. Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT04180488. Medical writing/editorial assistance was provided by Hodan Ibrahim, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guideline.

Disclosures: Maurer M: Allakos, Almirall, Amgen, AstraZeneca, Blueprint Medicines, Celldex Therapeutics, Faes Farma, Genentech, GI Innovation, Kyowa Kirin, LEO Pharma, Lilly, Merckle Recordati, Moxie Pharmaceutical, MSD, Novartis, Riemser, sanofi-aventis, Third Harmonic, Tribute Pharmaceuticals, UCB, Uriach – speaker and/or consultant and/or institutional research support. Kaplan A: Novartis, Genentech, Roche, AstraZeneca, Sanofi-Aventis, Abb-RISA, Phavaris, Biomarin, Celldex, and Annexon – speaker and/or consultant. Saini SS: NIH, Novartis, Regeneron Pharmaceuticals Inc. – research grants; Allakos, Aquestive, Celltrion, Escient Pharmaceuticals, GBIO, Genentech, GI Innovation, Granular Therapeutics, Innate Therapies, MedImmune, Novartis, Ono Pharmaceutical, Regeneron Pharmaceuticals Inc., Sanofi – consultant. Gimenez-Arnau A: Uriach Pharma, Sanofi, Genentech, Novartis, FAES, GSK, Thermo Fisher, Almirall, and Amgen, Instituto Carlos III-FEDER Menarini, Leo Pharma, GSK, MSD, Almirall, Avene – medical advisor, educational activities and/or institutional research support. Ensina LF: Novartis, Abbvie and Sanofi – speaker and/or consultant. Hide M: Kaken Pharmaceutical, Kyorin Pharmaceutical, Kyowa-Kirin, Mitsubishi Tanabe Pharma, MSD, Novartis, Sanofi, TAIHO Pharmaceutical and Teikoku Seiyaku and Uriach – speaker and/or consultant. Cyr S: Regeneron Pharmaceuticals, Inc. − employees and shareholders. Praestgaard A, Gonzalez T, Sugerman P: Sanofi − employees, may hold stock and/or stock options in the company.

Impact of Race on Efficacy and Safety of Secukinumab Among Patients With Hidradenitis Suppurativa: A Post-Hoc Analysis of the SUNSHINE and SUNRISE Trials

Tiffany Mayo¹, Julia M. Riley², Martina Porter³, Ryan Sullivan⁴, Ivette Alarcon⁵, Iryna Lobach⁵, Christine-Elke Ortmann⁵, Angela Llobet Martinez⁵; ¹Department of Dermatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA, ²Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, ³Department of Dermatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA, ⁴Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, ⁵Novartis Pharma AG, Basel, Switzerland.

Introduction: To evaluate the effect of race on the 52-week efficacy and safety of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS).

Study overview: This post-hoc analysis of pooled data from the phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials evaluated patients with HS by race (White [n=845], Asian [n=117], Black/African American [n=86], American Indian/Alaska Native [n=24], Native Hawaiian/Pacific Islander [n=1], and multiple [n=10]). By Week 52, patients received secukinumab per baseline randomization (300mg every 2 or 4 weeks [SECQ2W or SECQ4W, respectively]) or after switching from placebo at Week 16 (PBO-SECQ2W or PBO-SECQ4W). Efficacy was evaluated at Week 52 using HiSCR50 and other outcome measures as observed; safety was evaluated by the incidence of adverse events.

Results: At Week 52, the proportion of patients achieving HiSCR50 within each treatment group was generally similar, regardless of the race (White [SECQ2W, 62.6%; SECQ4W, 57.4%; PBO-SECQ2W, 51.5%; PBO-SECQ4W, 57.1%]; Asian [SECQ2W, 59.3%; SECQ4W, 56.3%; PBO-SECQ2W, 41.2%; PBO-SECQ4W, 25.0%]; Black/African American [SECQ2W, 57.9%; SECQ4W, 73.7%; PBO-SECQ2W, 80.0%; PBO-SECQ4W, 50.0%]; American Indian/Alaska Native [SECQ2W, 40.0%; SECQ4W, 83.3%; PBO-SECQ2W, 66.7%; PBO-SECQ4W, 80.0%]). Smaller subgroups (n≤10) were not represented in all treatment arms, although clinical improvements were observed. Variability was attributed to small subgroup sizes. Improvements in other efficacy measures and similar safety profiles were observed across race subgroups at Week 52.

Conclusions: Patients with moderate-to-severe HS who received secukinumab experienced improvements in disease activity and similar safety profiles at Week 52, regardless of race.

16-Week Results from FOREMOST, a Placebo-Controlled Study Involving Oligoarticular Psoriatic Arthritis Treated With Apremilast

Philip Mease¹, Dafna Gladman², Laura C. Coates³, Jacob Aelion⁴, Jitendra Vasandani⁵, Arthur Kavanaugh⁶, Joseph F. Merola⁷, Jyotsna Reddy⁸, Rebecca Wang⁸, Michele Brunori⁸, Stephen Colgan⁸, Laure Gossec⁹; ¹Swedish Medical Center, Seattle, WA, USA, ²Schroeder Arthritis Institute, Toronto, ON, Canada, ³University of Oxford, Oxford, UK, ⁴West Tennessee Research Institute, Jackson, TN, USA, ⁵West Texas Clinical Research, Lubbock, TX, USA, ⁶University of California, San Diego, School of Medicine, La Jolla, CA, USA, ⁷Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, ⁸Amgen Inc., Thousand Oaks, CA, USA, ⁹Sorbonne Université and Pitié Salpêtrière Hospital, Paris, France

Introduction: Oligoarticular psoriatic arthritis (PsA) can be associated with significant impact on quality of life, despite limited joint involvement. FOREMOST evaluated the efficacy of apremilast in patients with early PsA and limited joint involvement, using a modified minimal disease activity score (MDA-Joints).

Methods: FOREMOST (NCT03747939) is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with early PsA (≤5y) and limited joint involvement (>1–≤4 swollen and >1–≤4 tender joint count [SJC and TJC] of 66-68 assessed joints) were randomized 2:1 to receive apremilast or placebo for 24 weeks, with early escape at Week 16. Joints affected at baseline were defined as sentinel joints. Primary endpoint was proportion of patients at Week 16 who achieved MDA-Joints (SJC ≤1, TJC ≤1, and 3/5 disease-describing parameters). Secondary endpoints at Week 16 included: proportion of patients achieving Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) remission (REM, ≤4) or low disease activity (LDA, >4–≤13), Patient’s Global Assessment of Disease Activity (PtGA) ≤20, patient assessment of pain ≤15, Psoriatic Arthritis Disease Activity Score (PASDAS) good or moderate response, and change from baseline in Psoriatic Arthritis Impact of Disease 12-item (PsAID-12). Exploratory analyses were performed for all joints and post-hoc analyses in patients with 2–4 sentinel joints.

Results: In 308 randomized patients (apremilast: n=203, placebo: n=105) [age, mean 50.9 (SD 12.5) years; PsA duration, mean 9.9 (SD 10.2) months; baseline csDMARD use=39.9%], MDA-Joints response at 16 weeks was achieved by significantly more patients in the apremilast group than placebo (33.9% vs 16.0%, P=0.0008). At Week 16, a significantly greater proportion of patients achieved all secondary endpoints with apremilast vs placebo. In a post-hoc analysis of patients with ≤4 active joints at baseline (N=268, 87%), similar MDA-Joints response rates were seen in patients with 2–4 joints (apremilast: 34.4%, placebo: 17.2%) vs the overall study population at Week 16; there was also an increase in the proportion of patients who progressed to a joint count >4 through Week 16 among those receiving placebo (34.9%) but not apremilast (19.7%). No new safety signals were identified.

Conclusion: In FOREMOST—the first trial studying early oligoarticular PsA—apremilast showed significant efficacy with twice the MDA-Joint response at Week 16 vs placebo. A higher percentage of baseline oligoarticular patients progressed to polyarticular disease with placebo vs apremilast at Week 16.

Pooled Patient-reported Outcomes from the Phase 3 THRIVE-AA1 and THRIVE-AA2 Trials of Deuruxolitinib in Adult Patients with Moderate-to-severe Alopecia Areata

Natasha A. Mesinkovska¹, Maryanne Makredes Senna², Brett King³, Arash Mostaghimi⁴, Colleen Hamilton⁵, James Cassella⁵; ¹Department of Dermatology, University of California, Irvine, CA, US, ²Lahey Hair Loss Center of Excellence, Lahey Hospital and Medical Center, Burlington, MA, US, ³Department of Dermatology, Yale School of Medicine, New Haven, CT, US, ⁴Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, US, ⁵Sun Pharmaceutical Industries, Inc., Lexington, MA, US

Introduction: Alopecia areata (AA) is a chronic autoimmune hair loss disorder leading to reduced quality of life and considerable psychosocial impact. THRIVE-AA1 and THRIVE-AA2 were double-blind, placebo-controlled Phase 3 trials investigating deuruxolitinib, an oral JAK1/JAK2 inhibitor for treatment of moderate-to-severe AA. Both trials met their primary endpoint of Severity of Alopecia Tool (SALT) score ≤20. Pooled patient satisfaction results from these 2 trials are reported.

Methods: Eligible patients were 18–65 years of age with ≥50% scalp hair loss. A key secondary endpoint was percentage of responders who reported satisfaction on the hair Satisfaction Patient-Reported Outcome (SPRO) scale, a 5-point scale from “very dissatisfied (5)” to “very satisfied (1)” at Week 24.

Results: 1209 patients were randomized to placebo (n=267) or deuruxolitinib 8mg twice daily (BID; n=600) or 12mg BID (n=342). For the SPRO, 44.0% and 52.5% of the 8mg BID and 12mg BID groups, respectively, reported being “satisfied” or “very satisfied” with their scalp hair at Week 24 vs 3.3% for the placebo group (P <0.0001). Both doses of deuruxolitinib were also significantly different vs placebo at Week 24 on the patient global impression of severity (mean change from baseline, −2.1 and −2.5 for the 8mg BID and 12mg BID groups, respectively, vs −0.2 for the placebo group; P <0.0001) and improvement (54.2% and 66.6% reported improvements in the 8mg BID and 12mg BID groups, respectively, vs 6.1% for the placebo group; P <0.0001).

Conclusion: Patient satisfaction and impressions of severity and improvement of scalp hair from baseline were significantly higher for both doses of deuruxolitinib vs placebo.

Sponsorship: The study and medical writing support were funded by Sun Pharma.

Heatmap Evaluation of Body Hydration

Thu Q. Nguyen, PhD¹, Christine Emesiani, PharmD¹, Sindhu Garimella¹, Matthew Meckfessel, PhD¹; ¹Galderma Laboratories, L.P., Dallas, TX

Background: Evaluating moisturizers and their ability to adequately hydrate the skin, provides important information to guide clinicians in the recommendation of these products. This project was performed to visualize skin hydration via heatmap after use of a moisturizing cream (MC) and a moisturizing lotion (ML).

Methods: Split-body, intra-individual, open-label project in healthy volunteers with dry skin. Corneometer measurements were made at 30 pre-defined points around the elbow area, at baseline, 30 minutes post-application, one week, and four weeks. MC and ML were applied at least once daily for the entirety of the study. Heatmaps were generated using Python programming software to interpolate hydration values to colors that were then superimposed onto the volunteer’s body image. Digital photography and dermatoscopy photos were also taken.

Results: 5 subjects completed the study. There was a visible shift in skin hydration post-application of both MC and ML, and through 4-weeks of daily use as shown via corneometer measurements. Digital photography and dermatoscopy also showed a noticeable improvement in the skin’s appearance.

Conclusions: This innovative heatmap data generation showed a clear, visual change in hydration over time. There was a visible shift in hydration values from baseline to 30 minutes after application of the moisturizing cream and lotion, and hydration also showed consistent improvement 4 weeks after use of the products daily.

Funding source: Galderma Laboratories, LLP, Dallas, TX.

Efficacy and Safety of Brodalumab in Patients With Moderate-to-Severe Plaque Psoriasis and Inadequate Response to Prior Biologics

Kim Papp^1,2, Mark Lebwohl³, April Armstrong⁴, Seemal Desai^5,6, Robert Casquejo⁷, Abby Jacobson⁸; ¹Probity Medical Research, Waterloo, ON, Canada, ²University of Toronto, Toronto, ON, Canada, ³Icahn School of Medicine at Mount Sinai, New York, NY, USA, ⁴UCLA, Los Angeles, CA, USA, ⁵University of Texas Southwestern Medical Center, Dallas, TX, USA, ⁶Innovative Dermatology, Plano, TX, USA, ⁷Skin and Cancer Center of Scottsdale, Scottsdale, AZ, USA, ⁸Bausch Health Companies Inc, Bridgewater, NJ, USA

Introduction: Brodalumab is a human interleukin (IL)-17 receptor A antagonist indicated for adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy and, in the United States, have failed to respond or lost response to other systemic therapies. In phase 3 trials (AMAGINE-2/-3), ~35% of patients who failed ≥1 prior biologic achieved psoriasis area and severity index 100% improvement from baseline (PASI 100) after 16 weeks of brodalumab treatment. Here, we summarize efficacy and safety data of brodalumab in 2 studies of patients with inadequate response to prior biologics.

Methods: An open-label, phase 4 Canadian study (NCT04149587) in patients with inadequate response (determined by investigator) to ≥1 prior biologic (including anti–tumor necrosis factor α, IL-17A, IL-23, or IL-12/23 biologics) and an open-label, phase 4 US study (NCT03403036) in patients with inadequate response to anti–IL-17A biologics (defined as ≥3mo without achieving PASI 75 or 50% loss of original improvement) were included. Patients received brodalumab 210mg every 2 weeks. Efficacy data at week 16 are reported for consistency across studies. PASI and static physician’s global assessment (sPGA) data are combined unless otherwise noted; dermatology life quality index (DLQI) and psoriasis symptom inventory (PSI) data are from the Canadian study. Safety is reported at week 26 from the Canadian study.

Results: A total of 255 patients with evaluable data at week 16 were included (Canadian study, n=216; US study, n=39). Combined, 98 (38.4%) patients achieved PASI 100 and 133 (52.2%) patients achieved PASI 90 with brodalumab. Additionally, 176 (69.0%) patients achieved sPGA ratings of clear or almost clear. In the Canadian study, among 98 patients with prior inadequate response to anti–IL-17A, 35 (35.7%) and 48 (49.0%) achieved PASI 100 and PASI 90, respectively. Among 45 patients with prior inadequate response to anti–IL-23, 20 (44.4%) and 29 (64.4%) patients achieved PASI 100 and PASI 90, respectively. Percentage changes from baseline (95% CI) in DLQI and PSI were −67.6% (−73.5, −61.7; n=212) and −64.4% (−70.5, −58.3; n=216), respectively. Rates of treatment-emergent adverse events were consistent with the established safety profile of brodalumab, with no new safety signals and no reports of suicide or suicidal ideation.

Conclusion: Brodalumab, which blocks the IL-17 receptor for multiple inflammatory cytokines, was effective and well tolerated in patients with moderate-to-severe psoriasis and inadequate response to prior biologics, including those targeting IL-17A and IL-23. More than half of patients achieved clinically relevant PASI 90 and sPGA improvement.

Previous presentation: Data included in this abstract have been previously presented in full at the Fall Clinical Dermatology Conference; October 19-22, 2023; Las Vegas, NV.

Real-world Evidence Demonstrating Risk Stratification of the 31-GEP and i31-GEP in Patients with Stage I-III Cutaneous Melanoma

David Pariser, MD¹, Jeffrey Sussman, MD², Brian Martin, PhD³, Lindsay Ackerman, MD⁴, Craig Kraffert, MD⁵, Abel Jarell, MD⁶; ¹Virginia Clinical Research, Inc. and Eastern Virginia Medical School, Norfolk, VA, ²University of Cincinnati Medical Center, Cincinnati, OH, ³Castle Biosciences, Friendswood, TX, ⁴Medical Dermatology Specialists, Phoenix, AZ, ⁵CK Derm, Redding CA, ⁶SracSkin Research and Consulting, PLLC, Portsmouth, NH

Introduction: Current American Joint Committee on Cancer (AJCC 8^th edition) guidelines in patients with cutaneous melanoma (CM) separate them into risk categories based on the pathological tumor data of Breslow thickness, ulceration status, and sentinel lymph node status. The 31-gene expression profile was developed and prospectively validated to identify patients considered high or low risk by AJCC with low or high-risk tumor biology who may be over- or under-treated by current guidelines. To further advance personalized patient care, the 31-GEP result was integrated with clinical and pathological factors (i31-GEP for risk of recurrence, ROR) to provide a personalized, precise risk of tumor recurrence.

Methods: Patients with stage I-III CM enrolled in the CONNECTION study were prospectively tested with the 31-GEP between 2013 and 2017 (n=1,831). Kaplan-Meier analysis with the log-rank test was used to estimate survival differences between low (Class 1A), intermediate (Class 1B/2A), and high (Class 2) risk groups and the i31-GEP risk groups. The i31-GEP ROR combines Breslow thickness, ulceration, SLN status, mitotic rate, tumor location, age, and the 31-GEP result to provide a personalized estimate of recurrence-free survival (RFS). While guidelines have not established a ROR threshold for determining when to escalate or de-escalate care, the NCCN uses stage IIA versus IIB as the cut-point. This cut-point translates to a 5-year RFS rate of 69.8% and was used for the present analysis. Cox multivariable regression analysis was used to identify predictors of recurrence.

Results: Patients with a Class 1A result had higher 5-year RFS than those with a Class 1B/2A or Class 2B result (94.4% vs. 78.6% vs. 65.5%, P<0.001). The following were significant predictors of recurrence in multivariable analysis: Class 1B/2A (HR=2.07, P<0.001), Class 2B (HR=2.40, P<0.001), positive SLN (HR=4.54, P<0.001), Breslow thickness (HR=1.09, P=0.028), presence of ulceration (HR=1.57, P=0.005), mitotic rate >2/mm² (HR=1.47, P=0.016), and age (HR=1.02, P<0.001). Patients with a low-risk i31-GEP result had significantly higher 5-year RFS than those considered high risk by the i31-GEP (92.4% vs. 49.7%, P<0.001).

Conclusions: The i31-GEP is validated in a real-world group of prospectively tested patients. The independent i31-GEP ROR test result improves identification of patients whose management should be escalated or de-escalated within current guidelines.

The Impact of Sex on Treatment Response to Secukinumab for Patients With Hidradenitis Suppurativa: A Post-Hoc Analysis of the SUNSHINE and SUNRISE Trials

Christopher Sayed^1,2, Ziad Reguiai³, Jennifer L. Hsiao⁴, Stephanie Mehlis⁵, Eva Vilarrasa⁶, John Darcy⁷, Nicolas Thomas⁸, Iryna Lobach⁸, Christine-Elke Ortmann⁸, Angela Llobet Martinez⁸, Vivian Y. Shi⁹; ¹European Hidradenitis Suppurativa Foundation (EHSF), Dessau, Germany, ²University of North Carolina School of Medicine Department of Dermatology, Chapel Hill, North Carolina, USA, ³Dermatology Department, Polyclinique Courlancy-Bezannes, Reims, France, ⁴Department of Dermatology, University of Southern California, Los Angeles, California, USA, ⁵NorthShore University Health System, Skokie, Illinois, USA, ⁶Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, ⁷Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA, ⁸Novartis Pharma AG, Basel, Switzerland, ⁹Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Introduction: To evaluate the efficacy and safety of secukinumab at 52 weeks in patients with moderate-to-severe hidradenitis suppurativa (HS) grouped by sex.

Study overview: This post-hoc analysis included 610 female and 474 male patients with moderate-to-severe HS from the phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials. Patients received either secukinumab 300mg every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo (PBO) to Week 16. After Week 16, all patients received secukinumab (SECQ2W, SECQ4W, PBO-SECQ2W, or PBO-SECQ4W).¹ Efficacy was evaluated using Hidradenitis Suppurativa Clinical Response (HiSCR50), abscess and inflammatory nodule (AN) count, and other measures at Week 52. Pooled efficacy data from SUNSHINE and SUNRISE grouped by sex are reported as observed. Safety was evaluated by incidence of adverse events.

Results: High rates of HiSCR50 were observed at Week 52 for male and female patients, respectively, receiving SECQ2W (68.7% and 54.7%), SECQ4W (56.5% and 61.4%), PBO-SECQ2W (42.0% and 58.3%), and PBO-SECQ4W (54.3% and 51.5%). Improvements in AN count for males and females, respectively, were observed at Week 52 for patients receiving SECQ2W (−64.8% and −52.3%), SECQ4W (−56.6% and −59.1%), PBO-SECQ2W (−46.4% and −54.2%), and PBO-SECQ4W (−58.3% and −48.8%). Through Week 52, high proportions of men and women receiving SEC had no increase in draining tunnel count and most patients remained free from flare-ups. Safety profiles were similar between both sexes.

Conclusions: Both male and female patients with moderate-to-severe HS who received secukinumab experienced improvements in measures of disease activity with similar safety profiles at Week 52.

Reference:

Kimball AB, et al. Lancet. 2023;401:747-61.

Dupilumab Treatment Provides Long-Term Disease Control in Pediatric Patients With Moderate-to-Severe Atopic Dermatitis Over 1 Year

Elaine C. Siegfried^1,2, Eric L. Simpson³, Mark Boguniewicz^4,5, Carsten Flohr⁶, Lawrence F. Eichenfield^7,8, Andreas Pinter⁹, Michele Ramien^10,11, Xing-Hua Gao¹², Zhen Chen¹³, Lauren Bates¹³, Ana B. Rossi¹⁴; ¹Saint Louis University, St. Louis, MO, USA, ²Cardinal Glennon Children’s Hospital, St. Louis, MO, USA, ³Oregon Health & Science University, Portland, OR, USA, ⁴National Jewish Health, Denver, CO, USA, ⁵University of Colorado School of Medicine, Denver, CO, USA, ⁶Guy’s & St Thomas’ NHS Foundation Trust & King’s College London, UK, ⁷University of California, San Diego, CA, USA, ⁸Rady Children’s Hospital, San Diego, CA, USA, ⁹University Hospital Frankfurt am Main, Frankfurt am Main, Germany, ¹⁰Alberta Children’s Hospital, Calgary, AB, Canada, ¹¹University of Calgary, Calgary, AB, Canada, ¹²China Medical University, Shenyang, China, ¹³Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, ¹⁴Sanofi, Cambridge, MA, USA

Introduction: As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Here we evaluate the proportion of pediatric patients achieving EASI <7 (mild disease activity) across 5 visits during a 52-week open label extension trial of dupilumab.

Methods: Patients who previously participated in 16-week trials and were aged 0.5–5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6–11 years (LIBERTY AD PEDs; NCT03345914), and 12–17 years (LIBERTY AD ADOL; NCT03054428) were subsequently enrolled in the Phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300mg q4w or 200/300mg q2w (body weight <60 or ≥60kg, respectively). In this analysis, patients were assessed for maintenance of Eczema Area and Severity Index score <7 at 5 timepoints; Weeks 4, 16, 28, 40, and 52.

Results: In the 763 patients assessed, EASI <7 was maintained in at least 4 of 5 timepoints in most patients aged 0.5–5 years (N=173; 63%), 6–11 years (N=324; 58%), and 12–17 years (N=266; 50%). Across these age groups, 30–45% maintained this response for all 5 visits, and over 60% for at least 3 of 5 timepoints.

Conclusion: Most pediatric patients achieved sustained and consistent improvements in signs and area affected by AD during 1 year of treatment with dupilumab. Data suggest earlier intervention may provide improved disease control.

Funding sources: Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifier: NCT02612454.

Dupilumab Treatment Shows Consistent Improvement in Atopic Dermatitis in All Anatomical Regions in Patients Aged 6 Months to 17 Years: Results From an Open-Label Extension Study

Elaine C. Siegfried^1,2, Eric L. Simpson³, Michael J. Cork^4,5, Hidehisa Saeki⁶, Zhen Chen⁷, Elizabeth Simcox⁷, Randy Prescilla⁸; ¹Saint Louis University, St. Louis, MO, USA, ²Cardinal Glennon Children’s Hospital, St. Louis, MO, USA, ³Oregon Health & Science University, Portland, OR, USA, ⁴Sheffield Dermatology Research, University of Sheffield, Sheffield, UK, ⁵Sheffield’s Children’s Hospital, Sheffield, UK, ⁶Nippon Medical School, Tokyo, Japan, ⁷Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, ⁸Sanofi, Cambridge, MA, USA

Introduction: This analysis reports the impact of dupilumab treatment on atopic dermatitis (AD) signs across anatomical regions in patients aged 6 months to 17 years with AD in an open-label extension (OLE) study.

Methods: This ongoing, Phase 3 OLE (NCT02612454) enrolled patients aged 6 months to 17 years with moderate-to-severe AD who received a weight-tiered dupilumab regimen every 4 weeks (200mg: 5 to <15kg; 300mg: 15 to <30kg) or every 2 weeks (200mg: 30 to <60kg). This interim analysis reports unweighted Eczema Area and Severity Index (EASI) body region scores across anatomical regions (range 0–12) at baseline and Week 52.

Results: At baseline, 180 patients were included in the 6 months to 5 years group, 368 in the 6–11 years group, and 275 in the 12–17 years group. Unweighted mean (standard deviation [SD]) EASI body regions scores decreased in all anatomical regions in the 6 months to 5 years group (baseline/Week 52): head, 5.1 (3.2)/1.7 (1.9); trunk, 4.4 (3.2)/1.5 (2.0); upper extremities, 6.5 (3.5)/2.4 (2.7); lower extremities, 6.7 (3.4)/2.8 (2.6). Similar improvement was observed in the 6–11 years group: head, 4.3 (3.3)/1.7 (1.9); trunk, 3.6 (3.5)/1.2 (1.7); upper extremities, 6.0 (3.3)/3.0 (2.6); lower extremities, 6.0 (3.5)/2.8 (2.7); and in the 12–17 years group: head, 4.8 (3.1)/2.1 (2.3); trunk, 5.0 (3.3)/1.5 (2.2); upper extremities, 6.9 (3.2)/4.0 (3.2); lower extremities, 6.9 (3.4)/2.6 (2.9).

Conclusion: Dupilumab treatment provides sustained improvement in AD signs across all anatomical regions in children aged 6 months to 17 years with moderate-to-severe AD.

Funding sources: Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifier: NCT02612454.

Maintenance of Efficacy and Safety with Nemolizumab at Week 48: Results from Two Global Phase 3 Pivotal Studies (ARCADIA-1 and ARCADIA-2) in Patients with Moderate-to-severe Atopic Dermatitis

Jonathan I Silverberg, MD¹, Andreas Wollenberg, MD², Franz J. Legat, MD³, Vivian T. Laquer, MD⁴, April W. Armstrong, MD⁵, Pedro Herranz, MD⁶, Luigi Naldi, MD⁷, Faiz Ahmad, MD⁸, Liliana Ulianov, MD⁹, Christophe Piketty, MD⁹; ¹The George Washington University School of Medicine and Health Sciences, Washington, DC, ²Department of Dermatology and Allergy, Ludwig Maximillian University, Munich, Germany, ³Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria, ⁴The First OC Dermatology Research, Irvine, CA, ⁵Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, ⁶Department of Dermatology, University Hospital La Paz, Madrid, Spain, ⁷Academic Research Centre, Centro Studi GISED, Bergamo, Italy, ⁸Galderma Laboratories, Dallas, TX, ⁹Galderma R&D, Zug, Switzerland

Background: Atopic dermatitis (AD) is a common, chronic, and flaring itchy inflammatory skin disease requiring long-term treatment. Nemolizumab significantly improved skin lesions, itch, and sleep through Week (W) 16 in two global phase 3 studies (ARCADIA-1 [NCT03985943] and ARCADIA-2 [NCT03989349]) in adolescents and adults with moderate-to-severe AD.

Methods: This analysis pooled 32-week maintenance data from two double-blind, placebo controlled, phase 3 studies (N=507) in moderate-to-severe AD. Clinical responders (IGA 0/1 [clear/almost-clear] or EASI-75 [75% improvement in EASI score]) to nemolizumab at W16 were re-randomized (1:1:1) to receive nemolizumab 30mg every 4 weeks (Q4W), nemolizumab 30mg Q8W, or placebo (nemolizumab withdrawal) Q4W subcutaneously for further 32 weeks in combination with topical corticosteroids of low/medium potency and/or topical calcineurin inhibitors. Safety was assessed throughout the study.

Results: At W48, the proportion of patients who maintained IGA 0/1 response was 61.5% (nemolizumab-Q4W), 60.4% (nemolizumab-Q8W), and 49.7% (placebo); EASI-75 was maintained in 76.3% (nemolizumab-Q4W), 75.7% (nemolizumab-Q8W), and 63.9% (placebo); and itch response (≥4 points improvement in weekly average PPNRS) was achieved in 76.2% (nemolizumab-Q4W), 59.9% (nemolizumab-Q8W), and 42.1% (placebo). Similarly, response in sleep and quality of life was well maintained at W48. The safety profile was consistent across treatment arms; most treatment-emergent adverse events were non-serious and mild/moderate in intensity.

Conclusion: Among patients with clinical responses in skin lesions at W16, the majority maintained skin and itch responses at W48 with nemolizumab Q4W/Q8W. Nemolizumab was well-tolerated up to W48, and no safety signals were identified.

Integrated Safety Analysis of Abrocitinib in 3848 Patients With Moderate-To-Severe Atopic Dermatitis: Data From More Than 7000 Patient-Years With Up to 4.5 Years of Exposure

Eric L. Simpson¹, Jan Gutermuth^2,3, Marcus Maurer^4,5, Marjolein de Bruin-Weller⁶, Gary Chan⁷, Kanti Chittuluru⁸, Herwig Koppensteiner⁹, Haiyun Fan⁸, Justine Alderfer⁸, Shefali Vyas¹⁰; ¹Oregon Health & Science University, Portland, OR, USA, ²Skin Immunology & Immune Tolerance (SKIN) Research Group, Vrije Universiteit Brussel, Brussels, Belgium, ³Department of Dermatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium, ⁴Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, ⁵Fraunhofer Institute for Translational Medicine and Pharmacology, Immunology and Allergology, Berlin, Germany, ⁶National Expertise Center for Atopic Dermatitis; University Medical Center Utrecht, The Netherlands, ⁷Pfizer Inc., Groton, CT, USA, ⁸Pfizer Inc., Collegeville, PA, USA, ⁹Pfizer Corporation Austria GmbH, Vienna, Austria, ¹⁰Pfizer Inc., New York, NY, USA

Introduction: We present updated long-term integrated safety data in patients with moderate-to-severe atopic dermatitis (AD) and up to 4.5 years of abrocitinib exposure.

Methods: Analysis included patients from 8 phase 2/3 parent trials and 1 long-term extension trial (cutoff: September 25, 2022) in the JADE clinical program. Incidence rates (IRs; number of patients with events/100 patient-years [PY]) of adverse events of special interest (AESIs) were assessed in patients stratified by age, with or without cardiovascular (CV) risk factors and with atherosclerotic cardiovascular disease (ASCVD) risk score categorized as low (<5%), borderline (5%-7.4%), intermediate (7.5%-19.9%), or high (≥20%).

Results: Of 3848 patients in the pooled safety population, 3050 received the same abrocitinib dose throughout (consistent-dose cohort, described herein) and 798 patients comprised the variable-dose cohort (total of 7146.4 PY of abrocitinib exposure). Mean age of the consistent-dose cohort was 34 years; 5% of patients were aged ≥65 years and 1% were ≥75 years. IRs per 100 PY were numerically higher in older versus younger patients for death (18 to ≤40y: 0.08 [95% CI, 0.01-0.27], 40 to ≤65y: 0.21 [0.04-0.61], 65 to ≤75y: 2.11 [0.57-5.40], and ≥75y: 2.29 [0.06-12.77]) and major adverse CV events (MACE; 18 to ≤40y: 0.08 [0.01-0.27], 40 to ≤65y: 0.56 [0.24-1.10], 65 to ≤75y: 1.58 [0.33-4.63], and ≥75y: 2.29 [0.06-12.77]). Similar trends were observed for AESIs, including venous thromboembolism (VTE), malignancies (excluding nonmelanoma skin cancer), and serious infections (e.g., herpes zoster). IRs for MACE and VTE trended higher in older patients and those with CV risk factors. IRs for AESIs were generally higher in patients with intermediate or high ASCVD risk scores than those with low or borderline scores. Most deaths occurred in patients aged ≥65 years with ≥1 CV risk factor and were related to AESIs, including MACE, serious infection, and malignancy.

Conclusion: These long-term follow-up abrocitinib safety data with more than 7000 PY of exposure in patients with moderate-to-severe AD are consistent with the previously reported risk profile. No new safety signals were reported. AESI rates tended to be higher in older patients with ≥1 CV risk factor.

Pooled Efficacy, Patient-reported Outcomes, and Safety of Roflumilast Cream 0.15% from the INTEGUMENT-1 and INTEGUMENT-2 Phase 3 Trials of Adults and Children with Atopic Dermatitis

Eric Simpson¹, Mark Boguniewicz², Lawrence Eichenfield³, Mercedes E. Gonzales⁴, Adelaide A. Hebert⁵, Vimal H. Prajapati⁶, Melinda Gooderham⁷, David Krupa⁸, David H. Chu⁸, Robert C. Higham⁸, David R. Berk⁸; ¹Oregon Health & Science University, Portland, OR, USA, ²National Jewish Health, Denver, & University of Colorado School of Medicine, Aurora, CO, USA, ³Rady’s Children’s Hospital-San Diego, University of California, San Diego, CA, USA, ⁴Pediatric Skin Research, LLC, Miami, FL, USA, ⁵UT Health McGovern Medical School, Houston, TX, USA, ⁶Dermatology Research Institute, Probity Medical Research, Skin Health & Wellness Centre, and University of Calgary, Calgary, AB, Canada, ⁷SkiN Centre for Dermatology, Probity Medical Research, and Queen’s University, Peterborough, ON, Canada, ⁸Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA.

Introduction: Roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD).

Methods: We present pooled results from two identical phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged ≥6 years with mild to moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for 4 weeks. The primary endpoint was validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success (Clear/Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4. Patient-reported outcomes (PROs) were evaluated using the Worst Itch-Numeric Rating Scale (WI-NRS), SCORing AD (SCORAD), Patient-Oriented Eczema Measure, Dermatology Life Quality Index/Children’s Dermatology Life Quality Index, and the Dermatitis Family Impact questionnaire. Safety and tolerability were also evaluated.

Results: At Week 4, more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% vs. 14.1%, P<0.0001), WI-NRS Success (≥4‑point improvement on WI-NRS in patients aged ≥12 years with baseline WI-NRS ≥4; 31.9% vs. 16.6%, P<0.0001); and WI-NRS of 0/1 (in patients with baseline WI-NRS ≥2; 28.8% vs 18.5%, P=0.0087). At Week 4, roflumilast-treated patients improved more than vehicle-treated on the pruritus and sleep components of SCORAD (least squares mean percentage change −48.2% vs. −27.8%; [P<0.0001] and −47.9% vs. −22.9% [P<0.05], respectively). Differences favoring roflumilast were also seen for other secondary endpoints, including quality of life of the patient and family. Safety and local tolerability were favorable.

Conclusion: Once-daily, nonsteroidal roflumilast cream 0.15% improved PROs in patients with AD. Sponsored by Arcutis Biotherapeutics, Inc.

Rapid and Early Onset of Itch Relief with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to Two Years of Age with Atopic Dermatitis

Eric Simpson¹, Jonathan I. Silverberg², Robert Bissonnette³, Linda Stein Gold⁴, April Armstrong⁵, Adelaide A. Hebert⁶, Rocco T. Serrao⁷, Jeannette R. Jakus⁸, Philip M. Brown⁹, David S. Rubenstein⁹, Stephen C. Piscitelli⁹, Anna M. Tallman⁹, Lawrence F. Eichenfield¹⁰; ¹Oregon Health & Science University, Portland, OR, USA, ²The George Washington University School of Medicine and Health Sciences, Washington, DC, USA, ³Innovaderm Research Inc., Montreal, QC, Canada, ⁴Henry Ford Health System, Detroit, MI, USA, ⁵University of California Los Angeles, Los Angeles, CA, USA, ⁶UTHealth McGovern Medical School and Children’s Memorial Hermann Hospital, Houston, TX, USA, ⁷Dermatologists of Southwest Ohio, Mason, OH, USA, ⁸SUNY Downstate Health Sciences University, New York, NY, USA, ⁹Dermavant Sciences, Inc., Morrisville, NC, USA, ¹⁰University of California San Diego and Rady Children’s Hospital, San Diego, CA, USA

Introduction: Itch is the most bothersome symptom for patients with atopic dermatitis (AD). ADORING 1 and 2, two pivotal phase 3, double-blind, vehicle-controlled trials, tapinarof cream 1% once daily (QD) demonstrated efficacy and was well tolerated in adults and children down to 2 years of age with AD.

Objective: Evaluate time to onset of itch relief in the pivotal phase 3 trials.

Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis^TM score of ≥3 (moderate or severe), an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. Itch relief was assessed by changes in Peak Pruritus Numerical Rating Scale (PP-NRS) score, daily and by visit, from baseline through Week 8. PP-NRS considers itch over the past 24 hours; lower scores indicate less pruritus.

Results: 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean PP-NRS scores were 6.7 and 6.8 in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in mean PP-NRS scores for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application in ADORING 1 (–1.2 vs –0.9), and Day 2 in ADORING 2 (–1.6 vs –1.4). Daily itch improvements continued through Week 8 in both trials. Statistically significant reductions in mean weekly PP-NRS scores occurred as early as Week 1 (earliest assessment) with tapinarof versus vehicle (–2.0 vs –1.2 [P<0.0001]) and (–2.0 vs –1.3 [P=0.0010]) in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P<0.0001]).

Conclusion: Tapinarof cream 1% QD demonstrated rapid, significant, and clinically meaningful pruritus relief from 24 hours after initial application, with improvements increasing through Week 8 in both trials in adults and children down to 2 years with AD.

Funding support: Dermavant Sciences, Inc.

Nemolizumab Monotherapy Improves Itch and Skin Lesions in Patients with Moderate-to-severe Prurigo Nodularis: Results from a Global Phase 3 Trial (OLYMPIA 1)

Sonja Ständer, MD¹, Gil Yosipovitch, MD², Franz J. Legat, MD³, Adam Reich, MD⁴, Carle Paul, MD⁵, Dagmar Simon, MD⁶, Luigi Naldi, MD⁷, Xiaoxiao Chen, MSPH⁸, Zarif Jabbar Lopez, MD⁹, Christophe Piketty, MD⁹, Galderma R&D, Zug, Switzerland; Shawn G. Kwatra, MD¹⁰; ¹Center for Chronic Pruritus, University Hospital Münster, Münster, Germany, ²Miami Itch Center, Miller School of Medicine at the University of Miami, Miami, FL, ³Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria, ⁴Department of Dermatology, University of Rzeszów, Rzeszów, Poland, ⁵Department of Dermatology, Medical University of Toulouse, Toulouse, France, ⁶Department of Dermatology, Bern University Hospital, Bern, Switzerland, ⁷Academic Research Centre, Centro Studi GISED, Bergamo, Italy, ⁸Galderma Laboratories, L.P., Dallas, TX, ⁹Galderma R&D, Zug, Switzerland, ¹⁰Johns Hopkins Itch Center, Johns Hopkins University School of Medicine, Baltimore, MD

Abstract

Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by itch with multiple nodular skin lesions. We conducted a phase 3, multicenter, double-blind study, OLYMPIA 1 (NCT04501666) to assess the efficacy and safety of nemolizumab in moderate-to-sever PN after a 16-week treatment period. Eligible adults with PN (presenting ≥20 nodules, Investigator’s Global Assessment [IGA] score ≥3 [range 0-4] and Peak Pruritus Numerical Rating Scale [PP-NRS] score ≥7.0 [range 0-10] were randomized (2:1) to receive nemolizumab (N=190) or matching placebo (N=96). After an initial 60mg subcutaneous dose, patients received 30mg or 60mg (depending on baseline weight) every 4 weeks without topical treatment. Primary endpoints evaluated proportion of patients with a ≥4-point improvement in PP-NRS (itch-response) and IGA score 0/1 [clear/almost clear] with ≥2-grade improvement from baseline (IGA-success) at Week (W) 16. Key-secondary endpoint presented here is itch-response at W4. Prurigo Activity Score (PAS), a secondary endpoint, was evaluated throughout the study. All primary and key-secondary endpoints were met. Significantly (P<0.0001) greater proportion of nemolizumab- vs placebo-treated patients achieved itch-response at W4/W16 (41.3%/58.4% vs 6.3%/16.7%), and IGA-success (26.3% vs 7.3%) and ≥75% healed lesions (PAS item 5b: 41.1% vs 11.5%) at W16. Improvements in these responses were observed up to W24. Treatment-emergent adverse events (TEAEs) were reported in 71.7%/65.3% of nemolizumab-/placebo-treated patients. Nemolizumab monotherapy was well-tolerated and led to clinically meaningful and statistically significant improvements in core symptoms and signs of PN. These results confirm those of the previously reported Phase 3 study of nemolizumab (OLYMPIA 2).

Early and Sustained Efficacy of Fixed-Combination Halobetasol Propionate and Tazarotene Lotion in Participants with Moderate-to-Severe Scaling or Plaque Elevation

Linda Stein Gold¹, Emil Tanghetti², Edward Lain³, Andrea Murina⁴, Abby Jacobson⁵; ¹Henry Ford Health System, West Bloomfield, MI, ²Center for Dermatology and Laser Surgery, Sacramento, CA, ³Austin Institute for Clinical Research, Austin, TX, ⁴Tulane School of Medicine, New Orleans, LA, ⁵Ortho Dermatologics (a division of Bausch Health Companies Inc), Bridgewater, NJ

Background: Hyperkeratotic psoriasis produces plaques with extensive elevation and scaling and may be challenging to treat. Tazarotene-induced gene modulation may normalize the keratinocyte differentiation observed in psoriasis. This post hoc analysis of two phase 3 trials of fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) reports skin clearance as measured by the product of investigator’s global assessment and affected body surface area (IGA×BSA) in participants with moderate-to-severe scaling or plaque elevation.

Methods: Participants were randomized to once-daily HP/TAZ or vehicle lotion and evaluated at weeks 2 through 8 with posttreatment follow-up at week 12. Moderate-to-severe elevation or scaling was defined as baseline target plaque score of 3 (moderate) or 4 (severe) on a 0-to-4 scale. Outcomes included rate of ≥75% improvement from baseline in IGA×BSA (IGA×BSA-75; correlates with ≥75% improvement in psoriasis area and severity index) and percent change from baseline in IGA×BSA.

Results: Participants with moderate-to-severe scaling receiving HP/TAZ (n=240) achieved significantly greater rates of IGA×BSA-75 compared with vehicle (n=120), starting at week 2 (P=0.019) and sustained through week 12 (P<0.001). Additionally, significant improvements in percent change in IGA×BSA from baseline were observed as early as week 2 through week 12 (P<0.001, all time points). Similar significant improvements were observed in participants with moderate-to-severe plaque elevation receiving HP/TAZ (n=246) compared with vehicle (n=128).

Conclusions: HP/TAZ was associated with clinically meaningful, early, and sustained skin clearance in participants with hyperkeratotic psoriasis, as defined by moderate-to-severe scaling or plaque elevation, which is often difficult to treat.

Funding information: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and was funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health Companies Inc.

VISIBLE: Clearance and Symptom Improvement With Guselkumab at Week 16 in Skin of Color Participants With Moderate-to-Severe Plaque Psoriasis

Linda Stein Gold¹, Jensen Yeung^2-4, Adrian O. Rodriguez⁵, Jessica Vasquez⁶, Olivia Choi⁶, Katelyn Rowland⁶, Theodore Alkousakis⁶, Jenny Jeyarajah⁷, Javier Alonso-Llamazares⁸, Stephen Tyring⁹, April W. Armstrong¹⁰; ¹Henry Ford Health System, West Bloomfield, MI, USA, ²Women’s College Hospital, Toronto, ON, Canada, ³Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴Probity Medical Research, Waterloo, ON, Canada, ⁵Nashville Skin Comprehensive Dermatology Center, Nashville, TN, USA, ⁶Janssen Scientific Affairs, LLC, Horsham, PA, USA, ⁷Janssen Research & Development, LLC, Spring House, PA, USA, ⁸Driven Research, Coral Gables, FL, USA, ⁹Center for Clinical Studies, Webster, TX, USA, ¹⁰University of California Los Angeles, Los Angeles, CA, USA

Introduction: VISIBLE (NCT05272150) is an ongoing, first-of-its kind, large-scale, prospective, phase 3b, randomized, double-blind, placebo-controlled study to examine the efficacy and safety of guselkumab in skin of color participants with moderate-to-severe plaque psoriasis.

Procedure: Participants were randomized (3:1) to receive guselkumab 100mg or placebo at Weeks 0, 4, and then every 8 weeks. Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), and body surface area (BSA) results, along with participant health-related quality of life improvements as assessed by the Psoriasis Symptoms and Signs Diary (PSSD) were assessed at Week 16.

Results: At Week 16, the co-primary endpoints of IGA 0 (clear)/1 (almost clear) and 90% improvement from baseline on PASI score (PASI 90) were achieved by significantly higher proportions of participants treated with guselkumab compared with placebo (IGA 0/1, 74.0% vs 0%; PASI 90, 57.1% vs 3.8%; both P<0.001), as were IGA 0 (32.5% vs 0%; P<0.001) and PASI 100 or complete skin clearance (29.9% vs 0%; P<0.01). The proportions of guselkumab-treated participants achieving improvements in each PASI component (erythema, induration, scaling) were similar over time. In guselkumab and placebo groups, respectively, mean percent improvements from baseline were: 77.9% vs 0.9% for BSA, 84.5% vs 8.3% for PASI (both P<0.001). Mean changes from baseline in the PSSD symptom score were: guselkumab −49.4 vs placebo −8.2 (P<0.001), with a change of ≥40 considered clinically meaningful. Mean changes from baseline in individual PSSD symptom scores for guselkumab vs placebo were: redness, −6.2 vs −1.4; dryness, −4.9 vs −0.9; scaling, −6.2 vs −1.2 (all P<0.001). Overall safety was consistent with the established guselkumab safety profile, no new safety signals were identified.

Conclusion: After 3 doses of guselkumab, the majority of skin of color participants with moderate-to-severe plaque psoriasis achieved significantly clearer skin and reported clinically meaningful improvement in psoriasis symptoms.

Bimekizumab Efficacy from Treatment Initiation Through 4 years in Patients with Plaque Psoriasis: A Comprehensive, Long-term, Pooled Analysis from BE BRIGHT

Strober B.^1,2, Lebwohl M.³, Foley P.⁴, Langley R.G.⁵, Morita A.⁶, Piaserico S.⁷, Thirlwell J.^8,9, Szilagyi B.¹⁰, Hoepken B.¹⁰, Lambert J.¹¹, Thaçi D.¹²; ¹Department of Dermatology, Yale University, New Haven, CT, USA, ²Central Connecticut Dermatology Research, Cromwell, CT, USA, ³Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA, ⁴The University of Melbourne, St. Vincent’s Hospital Melbourne, Carlton, Victoria, Australia, ⁵Dalhousie University, Halifax, NS, Canada, ⁶Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, ⁷Dermatology Unit, Department of Medicine, Università di Padova, Padova, Italy, ⁸Allegis Group, Bracknell, UK, ⁹UCB Pharma, Slough, UK, ¹⁰UCB Pharma, Monheim, Germany, ¹¹UCB Pharma, Colombes, France, ¹²Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany

Introduction: Psoriasis is a chronic disease; assessing long-term treatment efficacy is imperative.¹ This study provided the first disclosure of efficacy responses from treatment initiation through to the end of 4 years of bimekizumab (BKZ) treatment in moderate-to-severe plaque psoriasis. Additionally, a comprehensive view of efficacy in BKZ-treated patients over 4 years across clinical and health-related quality of life outcomes was provided, using the largest available pool of 4-year global phase 3 clinical data at the time of this report.

Procedure: Data were pooled across the 52-week (wk) BE VIVID, 56-wk BE SURE and BE READY trials, and their OLE, BE BRIGHT.^2-5 Patients were randomized to BKZ 320mg every 4 wks (Q4W) to Wk16, received BKZ Q4W or Q8W thereafter, and entered the open label extension (OLE). Proportions achieving PASI90/PASI100 (≥90%/100% improvement from baseline in Psoriasis Area and Severity Index), body surface area (BSA) ≤1%, and Dermatology Life Quality Index (DLQI) 0/1 are reported from initial study baseline through to Year (Yr) 4 (OLE Wk144). Missing data were imputed using modified non-responder imputation: patients who discontinued due to lack of efficacy/treatment-related adverse events were considered non-responders at subsequent timepoints; multiple imputation used for other missing data.

Results: Among patients who received BKZ continuously from baseline and entered the OLE (N=771), 90.9%, 65.8%, 78.5%, and 71.5% achieved PASI90, PASI100, BSA≤1%, and DLQI 0/1, respectively, at Wk16. Responses were highly durable throughout 4 years’ BKZ treatment, with 86.1%, 64.7%, 79.8%, and 78.7% of patients reporting PASI90, PASI100, BSA≤1%, and DLQI 0/1 at Yr4. In the subset that received BKZ Q4W/Q8W/Q8W (initial/maintenance/OLE; N=197), 88.0%, 72.6%, 83.2%, and 83.3% reported PASI90, PASI100, BSA≤1%, and DLQ I0/1 at Yr4.

Conclusions: In this first disclosure of BKZ efficacy from treatment initiation through 4 years, high rates of clinical and health-related quality of life responses were achieved rapidly and were durable in the long-term.

References:

Mrowietz U et al. J Eur Acad Dermatol Venereol 2012;26 (Suppl. 2):12–20
Reich K et al. Lancet 2021;397:487–98, NCT03370133
Warren RB et al. N Engl J Med 2021;385:130–41, NCT03412747
Gordon KB et al. Lancet 2021;397:475–86, NCT03410992
Strober B et al. Br J Dermatol 2023;188:749–59, NCT03598790.

Funding: These studies were funded by UCB Pharma. Medical writing support was provided by Costello Medical.

Author Disclosures:

BSt: Consultant (honoraria): AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas, Dermavant, Eli Lilly and Company, Imagenebio, Janssen, Kangpu Pharmaceuticals, LEO Pharma, Maruho, Meiji Seika Pharma, Protagonist, Monte Carlo, Novartis, Pfizer, Rapt, Regeneron, Sanofi-Genzyme, SG Cowen, Sun Pharma, Takeda, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; stock options from Connect Biopharma, and Mindera Health; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, and Sanofi Genzyme; Scientific Co-Director (consulting fee): CorEvitas Psoriasis Registry; investigator for CorEvitas Psoriasis Registry; editor-in-chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis.

ML: Employee of Mount Sinai and receives research funds from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly and Company, Incyte, Inozyme, Janssen, LLC, , Ortho Dermatologics, Pfizer, Sanofi-Regeneron, and UCB Pharma; consultant for Almirall, AltruBio Inc., AnaptysBio, Apogee, Arcutis Inc., , AstraZeneca, Atomwise, Avotres, , Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, , Dermavant Sciences, EPI, Evommune Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, , Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, , Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi andVerrica.

PF: Grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; served as an investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly and Company, Evelo, Galderma, Geneseq, Genentech, GenesisCare, GSK, Hexima, Incyte, Janssen, Kymab, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Takeda, Teva, UCB Pharma, and Valeant; served on advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galderma, GSK, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Valeant; served as a consultant for Aslan, Bristol Myers Squibb, Eli Lilly and Company, Galderma, GenesisCare, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma, and Wintermute; received travel grants from AbbVie, Eli Lilly and Company, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sun Pharma, and Sanofi; served as a speaker for or received honoraria from AbbVie, Almirall, Amgen, Celgene, Eli Lilly and Company, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma, UCB Pharma, and Valeant.

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

AM: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly and Company, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Pharma, and Ushio.

SP: Served as consultant and/or speaker for AbbVie, Almirall, Celgene, Janssen, LEO Pharma, Eli Lilly and Company, Merck, Novartis, Pfizer, Sandoz, and UCB Pharma.

JT: Allegis Group statistical consultant for UCB Pharma.

BSz, BH, JL: Employees and shareholders of UCB Pharma.

DT: Served as an investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oreal, New Bridge, Novartis, Pfizer, Regeneron, Samsung, Sanofi, Target-RWE, UCB Pharma, and Vichy; received grants from AbbVie, LEO Pharma, and Novartis.

Deucravacitinib Efficacy at 4 years with Continuous Treatment in Week 52 PASI 90w Responders in the Phase 3 POETYK PSO-1 and PSO-2 Trials in Psoriasis

Bruce Strober¹, Howard Sofen², Shinichi Imaf*cku³, Carle Paul⁴, Melinda Gooderham⁵, Lynda Spelman⁶, Seong Jun Seo⁷, Thierry Passeron⁸, Renata M. Kisa⁹, Georgene Schroeder⁹, Matthew J. Colombo⁹, Subhashis Banerjee⁹, Matthias Augustin¹⁰, Andrew F. Alexis¹¹, Diamant Thaçi¹², Mark Lebwohl¹³, Eingun James Song¹⁴, Raja K. Sivamani¹⁵; ¹Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, CT, USA, ²University of California Los Angeles and Dermatology Research Associates, Los Angeles, CA, USA, ³f*ckuoka University Hospital, f*ckuoka, Japan, ⁴Toulouse University and CHU, Toulouse, France, ⁵SKiN Centre for Dermatology, Peterborough, Queen’s University, Kingston, and Probity Medical Research, Waterloo, ON, Canada, ⁶Veracity Clinical Research and Probity Medical Research, Brisbane, QLD, Australia, ⁷Soon Chun Hyang University Cheonan Hospital, Cheonan, South Korea, ⁸Université Côte d’Azur, University Hospital of Nice, Nice, France, ⁹Bristol Myers Squibb, Princeton, NJ, USA, ¹⁰University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ¹¹Weill Cornell Medicine, New York, NY, USA, ¹²University of Lübeck, Lübeck, Germany, ¹³Icahn School of Medicine at Mount Sinai, New York, NY, USA, ¹⁴Frontier Dermatology, Renton, WA, USA, ¹⁵Integrative Skin Science and Research, Sacramento, CA, USA

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials. At Week 52, patients in the parent PSO-1 and PSO-2 trials could enroll in the POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib 6mg once daily. This analysis evaluated the maintenance of high clinical responses among patients treated with continuous deucravacitinib through 4 years of therapy.

Methods: Efficacy through 4 years (Week 208; data cutoff, November 1, 2023) was evaluated in patients (n=513) who received continuous deucravacitinib treatment from Day 1 and who achieved a high clinical response (PASI 90 at Week 52) in the parent trials. Outcomes included ≥90%/100% reduction from baseline in PASI (PASI 90/100) and sPGA score of 0 (clear) or 0/1 (clear/almost clear). Data were analyzed as observed, by modified nonresponder imputation (mNRI), and by treatment failure rule (TFR).

Results: A total of 234 of 513 [45.6%] patients dosed with deucravacitinib from Day 1 achieved PASI 90 at Week 52. In the stringent mNRI analysis (n=231), the proportions of patients achieving PASI 90, PASI 100, sPGA 0, and sPGA 0/1 at Week 52 were 100.0%, 44.2%, 53.2%, and 91.3%. The proportions at Week 208 were 72.8%, 35.2%, 40.1%, and 79.4%, respectively. Results were similar by TFR methodology.

Conclusion: Clinical efficacy response rates for PASI and sPGA thresholds were generally maintained through 4 years in Week 52 PASI 90 responders. These results further support the long-term maintenance of efficacy of deucravacitinib in PASI 90 responders with moderate to severe plaque psoriasis.

Dupilumab Improves Health-Related Quality of Life and Work Productivity Among Adults With Moderate-to-Severe Atopic Dermatitis in Clinical Practice: 4-Year Follow-up Results From the RELIEVE-AD Study

Zhixiao Wang¹, Bruno Martins², Jingdong Chao¹, Min Yang², Kerry Noonan³, Brad Shumel¹, Debra Sierka⁴, Bruce Strober⁵; ¹Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, ²Analysis Group, Inc., Boston, MA, USA, ³Sanofi, Chilly-Mazarin, France, ⁴Sanofi, Cambridge, MA, USA, ⁵Yale University and Central Connecticut Dermatology, Cromwell, CT, USA

Background: RELIEVE-AD included adults with moderate-to-severe atopic dermatitis (AD) who initiated dupilumab in real-world clinical practice. Results showed improvements in symptoms, disease control, and treatment satisfaction, sustained through 4 years. Here we present 4-year data from RELIEVE-AD reporting on health-related quality of life (HRQoL) and work productivity (WP).

Methods: RELIEVE-AD was a single-arm, prospective, observational study of adults with moderate-to-severe AD who received dupilumab and agreed to participate in surveys at baseline and 1, 2, 3, 6, 9, 12, 33, and 48 months (M). Outcomes reported here are the Dermatology Life Quality Index (DLQI; range 0–30), evaluating HRQoL, and the Work Productivity and Activity Impairment-Atopic Dermatitis (WPAI-AD; range 0–100%) questionnaire, assessing productivity impact. Statistical significance, comparing each time point to baseline, was determined using generalized estimating equations to account for correlated data from the same patients.

Results: Among 698 patients completing the baseline survey, 353 (50.6%) completed the 48M survey. Patient demographics and clinical characteristics were similar for patients completing the 48M survey vs those completing the baseline survey. Mean DLQI score decreased from 14.4 at baseline to 3.0 at 48M and proportion of patients reporting no effect of AD on their lives (DLQI 0/1) increased from 1.1% to 55.2%. Mean Productivity Impairment decreased from 40.3% at baseline to 8.3% (48M), and Mean Total Activity Impairment decreased from 45.6% at baseline, to 9.1% (48M) (WPAI-AD score).

Conclusion: In real-world clinical practice, dupilumab treatment resulted in improvements in HRQoL and WP, sustained over 4 years of treatment.

Funding sources: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

Efficacy of Dupilumab Treatment in Atopic Hand and Foot Dermatitis Across Morphological Subtypes: Results From a Phase 3, Randomized, Double-blind, Placebo-controlled Trial

Margitta Worm¹, Eric L. Simpson², Golara Honari³, Weily Soong⁴, Andreas Pinter⁵, Koji Masuda⁶, Liyang Shao⁷, Ariane Dubost-Brama⁸, Ashish Bansal⁷, Andrew Korotzer⁷, Ana B. Rossi⁹; ¹Charité-Universitätsmedizin Berlin, Berlin, Germany, ²Oregon Health & Science University, Portland, OR, USA, ³Stanford University School of Medicine, Redwood City, CA, USA, ⁴Allervie Health/Alabama Allergy & Asthma Center, Birmingham, AL, USA, ⁵University Hospital Frankfurt am Main, Frankfurt am Main, Germany, ⁶Kyoto Prefectural University of Medicine, Kyoto, Japan, ⁷Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, ⁸Sanofi, Chilly-Mazarin, France, ⁹Sanofi, Cambridge, MA, USA

Background: Dupilumab has previously shown to significantly improve signs, symptoms, and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis. Here we evaluated the efficacy of dupilumab across morphological subtypes in patients with moderate-to-severe atopic hand and foot dermatitis.

Methods: The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300mg every 2 weeks (q2w) in adults; 200/300mg q2w in adolescents, or placebo for 16 weeks. This analysis reports the percent change from baseline in modified total lesion sign score (mTLSS) by hand and foot morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other.

Results: 133 patients enrolled into this study and were randomized to dupilumab (n=67) or placebo (n=66). Atopic hand and foot morphologies were reported in 3 categories: chronic dry fissured (n=63), hyperkeratotic (palmar/plantar; n=37), and other (n=33) In the “other” category, dyshidrotic was the most frequent morphology (n=13). mTLSS values were similar at baseline for all morphological subtypes. At Week 16, greater improvements were seen in the percent change from baseline (SE) in mTLSS for patients receiving dupilumab vs placebo in all categories: chronic dry fissured (−65.6% [5.1] vs −31.5% [6.2]), hyperkeratotic (palmar/plantar; −58.2% [7.6] vs −11.8% [7.7]), and other (−64.5% [11.6] vs −29.9% [9.0]). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis.

Conclusion: The efficacy of dupilumab remains consistent across different hand and foot dermatitis morphologies and shows higher treatment benefit across subtypes compared with placebo.

Funding sources: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifier: NCT04417894.

Improvement of Itch and Sleep Disturbance Symptoms in Patients With Moderate-to-Severe Atopic Dermatitis Treated With Lebrikizumab Is Maintained Over 52 Weeks as Measured Weekly With POEM

Gil Yosipovitch¹, Peter Lio^2,3, Franz J. Legat⁴, Mette Deleuran⁵, Raj Chovatiya², Evangeline Pierce⁶, Marta Casillas⁶, Yuxin Ding⁶, Fan Emily Yang⁶, Laia Bardolet⁷, Sonja Ständer⁸; ¹University of Miami Miller School of Medicine, Miami, Florida, USA, ²Northwestern University Feinberg School of Medicine, Illinois, USA, ³Medical Dermatology Associates of Chicago, Illinois, USA, ⁴Medical University of Graz, Graz, AUT, ⁵Department of Dermatology, Aarhus University Hospital, Aarhus, DNK, ⁶Eli Lilly and Company, Indiana, USA, ⁷Almirall, S.A., Barcelona, ESP, ⁸Center for Chronic Pruritus, University Hospital Münster, Germany

Introduction: Lebrikizumab demonstrated significant improvement versus placebo for measures of skin clearance and patient reported outcomes at weeks 16 and 52 in patients with atopic dermatitis. We report weekly maintained effect of lebrikizumab from weeks 16-52 on itch and sleep disturbance assessed by the Patient-Oriented Eczema Measure (POEM) in 2 phase 3 clinical trials.

Methods: In ADvocate1 and ADvocate2, week-16 responders (EASI75 or IGA 0/1 with ≥2-point improvement and without rescue medication) were re-randomized 2:2:1 to lebrikizumab every 2 weeks (LEBQ2W), every 4 weeks (LEBQ4W), or placebo for 36 additional weeks. This pooled analysis presents maintenance of improvement in patients achieving POEM response 0 (no days) or 1 (1-2d) for items 1 (itch) and 2 (sleep disturbance) from weekly electronic diaries for weeks 16-52 for LEBQ2W and LEBQ4W. Observed results exclude data collected after treatment discontinuation, rescue medication use, or patient transfer to escape arm.

Results: Proportions of patients responding 0/1 to POEM item 1 for LEBQ2W at weeks 16 and 52 were 35.9% (37/103) and 44.6% (29/65), respectively; LEBQ4W proportions were 39.3% (42/107) and 48.0% (36/75). Proportions of patients responding 0/1 to POEM item 2 for LEBQ2W at weeks 16 and 52 were 66.0% (68/103) and 83.1 (54/65), respectively; LEBQ4W proportions were 72.6% (77/106) and 78.4% (58/74). POEM responses of 0/1 for itch/sleep items were maintained week-by-week from the electronic diary.

Conclusion: POEM 0/1 responses for itch and sleep disturbance were maintained between patient study visits and improved over 52 weeks in lebrikizumab-treated patients, demonstrating maintenance of response for key AD symptoms.

Disclosure: Presented at American Academy of Dermatology, San Diego.

Lebrikizumab Monotherapy Maintained Improvement of Itch and Sleep-Loss Due to Itch After Two Years in Patients with Moderate-to-Severe Atopic Dermatitis

Gil Yosipovitch¹, Peter A. Lio², David Rosmarin³, Marta Casillas⁴, Fan Emily Yang⁴, Chaoran Hu⁴, Evangeline Pierce⁴, Laia Bardolet Boncompte⁵, Franz J. Legat⁶, Jose-Manuel Carrascosa⁷, Sonja Stander⁸; ¹Itch Center, Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami, Florida, USA, ²Northwestern University Feinberg School of Medicine; Medical Dermatology Associates of Chicago, Chicago, Illinois, USA, ³Indiana University School of Medicine, Indiana, USA, ⁴Eli Lilly and Company, Indianapolis, Indiana, USA, ⁵Almirall, Barcelona, Spain, ⁶Department of Dermatology, Medical University of Graz, Graz, Austria, ⁷Dermatology Department, Hospital Universitari Germans Trias i Pujol, UAB, IGTP, Badalona, Spain, ⁸Department of Dermatology and Center for Chronic Pruritus (KCP), University Hospital Münster, Münster, Germany

Introduction: Atopic dermatitis (AD) is a chronic disease with itch and sleep-loss due to itch as key symptoms, which requires long-term treatment and sustained response. We describe the impact of lebrikizumab on itch and sleep-loss due to itch at 104-weeks in a long-term extension study, ADjoin.

Methods: Responders from monotherapy ADvocate1&2 (achieved Eczema Area and Severity Index 75 or Investigator Global Assessment score (0,1), without rescue medication), who completed ADvocate1&2 and enrolled into ADjoin, received LEB 250mg every 2-weeks (Q2W) or 4-weeks (Q4W) for an additional 52-weeks. Itch was assessed using Pruritus Numeric Rating Scale (NRS), an 11-point scale [0 (no itch) to 10 (worst imaginable itch)]. Sleep-loss due to itch was assessed using Sleep-Loss Scale (SLS), a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Outcomes are reported as observed at Week 104: change from baseline (CFB), Pruritus NRS (0,1), ≥3-point improvement in Pruritus NRS, ≥1-point and ≥2-point improvement in SLS. ADvocate1&2 data were pooled.

Results: At Week 104, CFB in Pruritus NRS was −5.24 Q2W and −5.06 Q4W, Pruritus NRS (0,1) was 57.4% Q2W and 55.4% Q4W, and ≥3-point improvement in Pruritus NRS was 85.2% Q2W and 85.5% Q4W. At Week 104, CFB in SLS was −1.78 Q2W and −1.52 Q4W, ≥1-point improvement in SLS was 93.0% Q2W and 94.0% Q4W and ≥2-point improvement in SLS was 64.3% Q2W and 71.4% Q4W.

Conclusion: Patients with moderate-to-severe AD achieved and maintained improvement of itch and sleep-loss due to itch after two-years of treatment with lebrikizumab monotherapy.

Disclosure: Presented at American Academy of Dermatology, San Diego.

Society of Dermatology Physician Assistants: Abstracts from ... : Journal of Dermatology for Physician Assistants (2024)

References

https://journals.lww.com/jdpa/fulltext/9900/society_of_dermatology_physician_assistants_.17.aspx