Selected Abstracts from Elevate-Derm East Conference | JCAD | The Journal of Clinical and Aesthetic Dermatology (2024)

J Clin Aesthet Dermatol. 2024;17(7–8 Suppl 1):S27–S36.

Acne

Efficacy and safety of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel in participants with moderate-to-severe acne: the patient journey

Presenters: Hilary Baldwin, MD;¹ Julie C. Harper, MD;² Joshua A. Zeichner, MD;³ Zoe D. Draelos, MD;⁴ Lawrence F. Eichenfield, MD;⁵ Michael Gold, MD;⁶ Linda Stein Gold, MD;⁷ Leon H. Kircik, MD³

Affiliations: ¹The Acne Treatment and Research Center, Brooklyn, NY; ²Dermatology & Skin Care Center of Birmingham, Birmingham, AL; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Dermatology Consulting Services, PLLC, High Point, NC; ⁵University of California, San Diego School of Medicine, La Jolla, CA; ⁶Tennessee Clinical Research Center, Nashville, TN; ⁷Henry Ford Hospital, Detroit, MI

Introduction: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for the treatment of acne. In three published clinical studies of participants with moderate-to-severe acne, CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety/tolerability. Herein are presented detailed efficacy and safety data by visit from five clinical study patients to document their treatment journey with CAB.

Methods: In two Phase III (NCT04214652, NCT04214639) randomized, double-blind, 12-week studies, participants aged nine years or older with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Endpoints included percentage of participants achieving treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin) and percent change from baseline in inflammatory/noninflammatory lesion counts at Week 12. Dosing compliance, treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also assessed. Descriptive efficacy, safety, and tolerability data from each of the selected cases who completed 12 weeks of CAB treatment are summarized.

Results: Participants (n=5) were male or female, White or Asian, and Hispanic or non-Hispanic/Latino. Two participants had moderate acne at baseline and three had severe acne. Ages ranged from 13 to 32 years. All participants were compliant with CAB treatment (>96%). At Week 12, three participants achieved treatment success, one achieved a two-grade reduction from baseline, and one had a one-grade reduction from moderate to mild. Percent reductions from baseline to Week 12 in inflammatory and noninflammatory lesion counts ranged from 74.7 to 100 percent. No participants reported TEAEs or serious AEs. Scores on some cutaneous safety and tolerability assessments increased at Weeks 2, 4, or 8, but generally decreased back to or below baseline levels by Week 12.

Conclusions: In the overall Phase III clinical trials, fixed-dose, triple-combination CAB gel has demonstrated good efficacy, safety, and tolerability. All cases presented here achieved substantial (>70%) acne lesion reductions, with four of the five achieving treatment success or a two-grade reduction in EGSS by Week 12. While cutaneous safety/tolerability patterns were variable across cases, transient increases with CAB generally resolved to baseline values within two months of treatment. These clinical study cases reinforce the importance of patient education regarding the efficacy and safety of acne treatment, including the importance of treatment adherence, managing patient expectations, and the potential for transient increased cutaneous effects.

Funding/financial disclosures: Ortho Dermatologics.

Atopic Dermatitis

Dupilumab improves patient-reported symptom control among adults with moderate-to-severe atopic dermatitis in clinical practice: 4-year follow-up results from the RELIEVE-AD study

Presenters: Zhixiao Wang,¹ Min Yang,² Jingdong Chao,¹ Bruno Martins,² Gaelle Bego-Le-Bagousse,³ Brad Shumel,¹ Debra Sierka,⁴ Bruce Strober⁵

Affiliations: ¹Regeneron Pharmaceuticals Inc., Tarrytown, NY; ²Dermatology Group, Boston, MA; ³Sanofi, Gentilly, France; ⁴Sanofi, Cambridge, MA; ⁵Yale University and Central Connecticut Dermatology, Cromwell, CT

Introduction: Atopic dermatitis (AD) is often perceived to be a childhood disease, but it can also have a highly detrimental impact among adults. Results from the RELIEVE-AD study, which included adults with moderate-to-severe AD who initiated dupilumab in real-world clinical practice, showed significant, sustained improvements in disease control, flares, skin symptoms, sleep, quality of life, treatment satisfaction, and concomitant AD medications up to three years.^1–3 The aim of this study is to report four-year patient-reported symptom control from RELIEVE-AD.

Methods: RELIEVE-AD is a single-arm, prospective, longitudinal patient survey study of adults with moderate-to-severe AD who were prescribed dupilumab, enrolled in the United States (US) dupilumab patient support program, and agreed to participate in online surveys at baseline and Months 1, 2, 3, 6, 9, 12, 33, and 48. Outcomes presented here are: global change in itch since treatment initiation; absence of flares (increased itching/redness and/or new/spreading lesions) in the previous four weeks; skin symptoms (pain, hot/burning, sensitivity) severity in the past week (0 [no symptoms] to 10 [worst symptoms]); and AD-related sleep problems in the past week. Statistical significance was determined using generalized estimating equations to account for correlated data from the same patients. Normal distributions with an identity link function were used for continuous outcomes; binomial distributions with a logit link function were used for categorical outcomes.

Results: Among 698 patients who completed the baseline survey, 353 (50.6%) completed the Month 48 survey. At baseline, the mean age was 46.2 years, 61.7 percent of patients were female, and common comorbidities included nonseasonal allergies (36.0%), asthma (32.2%), and hypertension (26.9%). Over 75 percent of patients reported that their itch was “very much better” at Month 48 in comparison to baseline. Flare-free status over the previous four weeks increased from three percent at baseline to 33.8 percent at Month 1 and 43.5, 45.9, and 49.0 percent at Months 12, 33, and 48, respectively (all p<0.001). Skin symptoms improved considerably from baseline to Month 1, further improving up to Month 48 (p<0.001). Similarly, AD-related sleep problems in the past week were reported by 77.5 percent of patients at baseline, falling to 27.1 percent at Month 1 and 14.1, 13.4, and 12.7 percent at Months 12, 33, and 48, respectively (all p<0.001). Only 50.6 percent of patients were evaluable at Month 48.

Conclusion: Dupilumab treatment in real-world clinical practice led to rapid and sustained improvements in multiple patient-reported AD symptoms (itch, flares, skin symptoms, and sleep problems) over four years, with similar benefits at four years compared to those previously reported at one and three years.

References:

1. Strober B, et al. JAMA Dermatol. 2022;158(2):142–150.
2. Strober B, et al. JAAD. 2022;87(3 Suppl): AB47 (abstract 33120), AB159 (abstract 33322).
3. Delevry D, et al. JAAD. 2022;87(3 Suppl): AB45 (abstract 32929), AB179 (abstract 33325).

Dupilumab reduces atopic dermatitis lesion severity and extent in children <12 years of age with moderate-to-severe AD: interim results from the PEDISTAD real-world registry

Presenters: Lara Wine Lee,¹ Alan D. Irvine,² Michele Ramien,^3,4 Danielle Marcoux,^5,6 Eulalia Baselga,⁷ Marlies de Graaf,⁸ Martti Antila,⁹ Nelson A. Rosario Filho,¹⁰ Irene Lara-Corrales,¹¹ Joel C. Joyce,¹² Rajan Gupta,¹³ Patrick Redman,¹⁴ Annie Zhang¹³

Affiliations: ¹Medical University of South Carolina, Charleston, SC; ²Trinity College Dublin, Dublin, Ireland; ³Alberta Children’s Hospital, Calgary, AB, Canada; ⁴University of Calgary, Calgary, AB, Canada; ⁵University of Montreal, Montreal, QC, Canada; ⁶CHU Sainte-Justine University Hospital Center, Montreal, QC, Canada; ⁷Hospital Sant Joan de Déu, Barcelona, Spain; ⁸University Medical Center Utrecht, Utrecht, Netherlands; ⁹Clínica de Alergia, Sorocaba, Sao Paulo, Brazil; ¹⁰Federal University of Paraná, Curitiba, Brazil; ¹¹The Hospital for Sick Children, Toronto, ON, Canada; ¹²Endeavor Health, Skokie, IL; ¹³Sanofi, Cambridge, MA; ¹⁴Regeneron Pharmaceutical Inc., Tarrytown, NY

Introduction: In clinical trials, dupilumab has consistently improved disease severity in children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to investigate the impact of systemic treatments on the individual anatomical regions that comprise the Eczema Area and Severity Index (EASI).

Methods: PEDISTAD (NCT03687359) is an international, longitudinal, observational, 10-year registry study of patients aged under 12 years with moderate-to-severe AD. This interim analysis reports mean EASI scores of the head and neck and upper limbs at therapy start and last observation.

Results: A total of 207 patients received dupilumab, 127 received methotrexate, and 139 received cyclosporine. The mean observation period was 17.0, 18.7, and 14.3 months for dupilumab, methotrexate, and cyclosporine, respectively. Mean (standard deviation [SD]) EASI scores for the head and neck area of dupilumab patients improved from 2.0 (0.2) at therapy start to 0.7 (0.1) at last observation. Improvement was also seen in patients receiving methotrexate (therapy start: 2.0 [0.2]; last observation: 1.0 [0.2]) and cyclosporine (therapy start: 2.2 [0.2]; last observation: 1.6 [0.2]). A numerically greater improvement in mean (SD) EASI scores of the upper limbs was observed in patients receiving dupilumab (therapy start: 4.5 [0.2]; last observation: 1.5 [0.2]), compared to methotrexate (therapy start: 3.8 [0.2]; last observation: 2.1 [0.2]) and cyclosporine (therapy start: 4.1 [0.2]; last observation: 2.9 [0.3]). Adverse events were experienced by 23.7, 30.5, and 32.6 percent of patients receiving dupilumab, methotrexate, and cyclosporine, respectively.

Conclusion: Children with moderate-to-severe AD receiving dupilumab, methotrexate, or cyclosporine had improvements in AD lesion severity and extent in individual anatomical regions, with the greatest numerical improvement observed in those receiving dupilumab.

Dupilumab treatment for up to 5 years improves clinical signs across all anatomical regions in adults with moderate-to-severe atopic dermatitis

Presenters: Lisa A. Beck,¹ Robert Bissonnette,² Mette Deleuran,³ Takeshi Nakahara,⁴ Ryszard Galus,⁵ Zhen Chen,⁶ Elena Avetisova,⁶ Ariane Dubost-Brama,⁷ Arsalan Shabbir⁶

Affiliations: ¹University of Rochester Medical Center, Rochester, NY; ²Innovaderm Research, Montreal, QC, Canada; ³Aarhus University Hospital, Aarhus, Denmark; ⁴Kyushu University, f*ckuoka, Japan; ⁵Medical University of Warsaw, Warsaw, Poland; ⁶Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁷Sanofi, Chilly-Mazarin, France

Introduction: Therapeutic goals for atopic dermatitis (AD), a chronic inflammatory disease, include amelioration of clinical signs. We analyzed the extent of improvement in AD signs across anatomical regions in adults with moderate-to-severe AD who had received dupilumab treatment for up to five years.

Methods: Adults with moderate-to-severe AD who had participated in any dupilumab parent study in AD were enrolled, for up to five years, in the LIBERTY AD open-label extension study (NCT01949311) and treated with 300mg dupilumab weekly. In total, 226 patients transitioned to 300mg every two weeks (q2w) to align with approved dosage (mean [standard deviation] q2w exposure: 66.4 [21.6] weeks). Concomitant topical treatments for AD were permitted, including topical corticosteroids and topical calcineurin inhibitors. AD clinical signs (erythema, edema/papulation, excoriation, and lichenification) across anatomical regions were assessed using Eczema Area and Severity Index (EASI) scores. Data are presented as observed for the overall study population (N=2,677).

Results: In total, 2,207/362/334 patients completed up to 52/172/260 weeks of treatment, respectively. Reduction in mean percentage change in EASI score from parent study baseline at end of study (ES) indicated improved AD clinical signs across all anatomical regions. Erythema improvement at ES was: head and neck, 69.2 percent; trunk, 78.6 percent; upper extremities, 74.0 percent; and lower extremities, 84.5 percent. Edema/papulation improvement at ES was: head and neck, 76.3 percent; trunk, 82.8 percent; upper extremities, 80.8 percent; and lower extremities, 88.3 percent. Excoriation improvement at ES was: head and neck, 88.5 percent; trunk, 90.4 percent; upper extremities, 89.8 percent; and lower extremities, 91.6 percent. Lichenification improvement at ES was: head and neck, 78.0 percent; trunk, 84.3 percent; upper extremities, 79.0 percent; and lower extremities, 85.9 percent. Safety data were consistent with the known dupilumab safety profile in patients with AD.

Conclusion: Long-term dupilumab treatment for up to five years improved clinical signs across all anatomical regions in adults with moderate-to-severe AD. Safety data were consistent with prior studies.

Pooled efficacy, patient-reported outcomes, and safety of roflumilast cream 0.15% from the INTEGUMENT-1 and INTEGUMENT-2 Phase III trials of adults and children with atopic dermatitis

Presenter: Eric Simpson,¹ Mark Boguniewicz,² Lawrence Eichenfield,³ Mercedes E. Gonzales,⁴ Adelaide A. Hebert,⁵ Vimal H. Prajapati,⁶ Melinda Gooderham,⁷ David Krupa,⁸ David H. Chu,⁸ Robert C. Higham,⁸ David R. Berk⁸

Affiliations: ¹Oregon Health & Science University, Portland, OR; ²National Jewish Health, Denver and University of Colorado School of Medicine, Aurora, CO; ³Rady’s Children’s Hospital-San Diego, University of California, San Diego, CA; ⁴Pediatric Skin Research, LLC, Miami, FL; ⁵UT Health McGovern Medical School, Houston, TX; 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

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 III randomized, controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged six years or older with mild-to-moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for four weeks. The primary endpoint was validated Investigator’s 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 patients 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.

Funding/financial disclosures: Sponsored by Arcutis Biotherapeutics, Inc.

Tapinarof cream 1% once daily: consistent efficacy across disease severity and age subgroups in the treatment of adults and children down to 2 years of age with atopic dermatitis

Presenters: Luz Fonacier,¹ Mark Boguniewicz,² Jason Ohayon,³ Philip M. Brown,⁴ David S. Rubenstein,⁴ Anna M. Tallman,⁴ Jonathan I. Silverberg⁵

Affiliations: ¹NYU Long Island School of Medicine, Mineola, NY; ²National Jewish Health and University of Colorado School of Medicine, Denver, CO; ³Hamilton Allergy and McMaster University, Hamilton, ON, Canada; ⁴Dermavant Sciences, Inc., Morrisville, NC; ⁵The George Washington University School of Medicine and Health Sciences, Washington, DC

Introduction: Atopic dermatitis (AD) presents a spectrum of clinical phenotypes. In ADORING 1 and ADORING 2, two identical, pivotal, Phase III, double-blind, vehicle-controlled trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated statistically significant efficacy and was well tolerated in adults and children down to two years of age with AD. Here, we report efficacy with tapinarof cream by baseline disease severity and age in ADORING 1 and 2.

Methods: Patients with a Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or greater (moderate or severe), an Eczema Area and Severity Index (EASI) score of 6 or greater, and body surface area (BSA) involvement of 5 to 35 percent were randomized to tapinarof cream or vehicle QD for eight weeks. A 75-percent or greater improvement in EASI (EASI75) score from baseline at Week 8 was a secondary efficacy endpoint.

Results: A total of 407 and 406 patients were randomized in ADORING 1 and 2, respectively. At baseline, 84.0 to 89.9 percent of patients had a vIGA-AD score of 3, mean EASI score was 12.5 to 13.3, and mean BSA affected was 16.7 to 16.9 percent across trials. A high proportion of patients achieved an EASI75 response at Week 8 with tapinarof versus vehicle in both trials, 55.8 percent versus 22.9 percent and 59.1 percent versus 21.2 percent (both statistically significant; p<0.0001). The magnitude of EASI75 response with tapinarof versus vehicle was consistent in both trials, respectively, regardless of baseline disease severity (moderate AD, 58.8% and 59.9% vs. 25.7% and 24.3%; severe AD, 54.5% and 69.3% vs. 6.9% and 7.6%). Consistent efficacy was observed across all age groups with tapinarof versus vehicle in both trials (2–6 years, 72.1% and 68.1% vs. 17.0% and 24.8%; 7–11 years, 52.1% and 55.3% vs. 28.0% and 35.1%; 12–17 years, 54.3% and 68.1% vs. 24.5% and 13.5%; and ≥18 years, 52.5% and 49.2% vs. 26.2% and 15.1%). The most frequent adverse events were folliculitis, headache, and nasopharyngitis.

Conclusion: Tapinarof cream 1% QD demonstrated consistent, clinically meaningful efficacy across disease severity and age subgroups and was well tolerated in adults and children down to two years of age.

Funding/financial disclosures: Dermavant Sciences, Inc.

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 III trials

Presenters: Andrew F. Alexis,¹ Leon Kircik,² Raj Chovatiya,^3,4 Zakiya P. Rice,⁵ Tina Bhutani,⁶ Philip M. Brown,⁷ Stephen C. Piscitelli,⁷ David S. Rubenstein,⁷ Anna M. Tallman,⁷ April W. Armstrong⁸

Affiliations: ¹Weill Cornell Medical College, New York, NY; ²Icahn School of Medicine at Mount Sinai, New York, NY; ³Rosalind Franklin University Chicago Medical School, North Chicago, IL; ⁴Center for Medical Dermatology and Immunology Research, Chicago, IL; ⁵Dermatology Associates of Georgia, Atlanta, GA; ⁶University of California, San Francisco, CA; ⁷Dermavant Sciences, Inc., Morrisville, NC; ⁸University of California Los Angeles, Los Angeles, CA

Introduction: Patients with atopic dermatitis (AD) and skin of color can have heterogeneous presentations and treatment responses. In the pivotal Phase III ADORING 1 and ADORING 2 trials, tapinarof (VTAMA®, Dermavant Sciences, Inc.) cream 1% once daily (QD) was significantly efficacious and well tolerated versus vehicle in adults and children down to two years of age with AD. Here, we report efficacy by skin color based on patients’ self-identified race and investigator-assessed Fitzpatrick skin type.

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

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

Conclusion: Tapinarof cream 1% QD was consistently efficacious among all racial groups and Fitzpatrick skin types, including adults and children down to two years of age with AD and skin of color, who comprised approximately 50 percent of patients in these trials.

Funding/financial disclosures: Dermavant Sciences, Inc.

Melanoma

Real-world evidence demonstrating risk stratification of the 31-GEP and i31-GEP in patients with Stage I–III cutaneous melanoma

Presenters: David Pariser, MD;¹ Jeffrey Sussman, MD;² Brian Martin, PhD;³ Lindsay Ackerman, MD;⁴ Craig Kraffert, MD;⁵ Abel Jarell, MD⁶

Affiliations: 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 8th 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 (SLN) status. The 31-gene expression profile (GEP) test 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 undertreated by current guidelines. To further advance personalized patient care, the 31-GEP test 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 to III CM enrolled in the CONNECTION study were prospectively tested with the 31-GEP test 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-risk (Class 2) 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 test 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 National Comprehensive Cancer Network (NCCN) uses Stage IIA versus IIB as the cut-point. This cut-point translates to a five-year RFS rate of 69.8 percent 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 five-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 (hazard ratio [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 greater than 2/mm² (HR=1.47, p=0.016), and age (HR=1.02, p<0.001). Patients with a low-risk i31GEP test result had significantly higher five-year RFS than those considered high risk by the i31-GEP test (92.4% vs. 49.7%, p<0.001).

Conclusions: The i31-GEP test 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.

Psoriasis

A Phase IIb, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER-2

Presenters: Laura Korb Ferris,¹ Jerry Bagel,² Yu-Huei Huang,³ Andrew Pink,⁴ Stephen K. Tyring,⁵ Georgios Kokolakis,⁶ Amy M. DeLozier,⁷ Shu Li,⁸ Yaung-Kaung Shen,⁸ Takayuki Ota,⁷ Robert Bissonnette⁹

Affiliations: ¹University of Pittsburgh, Pittsburgh, PA; ²Psoriasis Treatment Center of Central NJ, East Windsor, NJ; ³Department of Dermatology at Chang Gung Memorial Hospital and the School of Medicine at Chang Gung University, Taoyuan City, Taiwan; ⁴St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK; ⁵Center for Clinical Studies, Webster, TX; 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; ⁸Janssen Research & Development, Spring House, PA; ⁹Innovaderm Research, Montreal, QC, Canada

Introduction: JNJ-77242113, a targeted oral peptide, inhibits interleukin (IL)-23 signaling by binding the IL-23 receptor. JNJ-77242113 showed superior efficacy versus placebo in moderate-to-severe psoriasis in FRONTIER-1.¹ FRONTIER-2 was a Phase IIb long-term extension study, during which the patients from FRONTIER-1 who entered the long-term extension were evaluated over a period of one year.

Methods: 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 placebo through Week (W) 16. In FRONTIER-2, patients completing FRONTIER-1 (W16) continued assigned dose through W52; those randomized to placebo crossed over to JNJ-77242113 100mg QD (PBO to 100mg). The primary endpoint was the proportion of patients achieving 75-percent or greater improvement in Psoriasis Area and Severity Index (PASI75) at W52. Response rates were estimated using nonresponder imputation and FRONTIER-1 baseline data.

Results: At W52, the proportions of patients achieving PASI75 with JNJ-77242113 were 48.8 percent for 25mg QD, 58.5 percent for 25mg BID, 69.8 percent for 50mg QD, 65.1 percent for 100mg QD, 76.2 percent for 100mg BID, and 65.7 percent for PBO to 100mg; corresponding rates for PASI90/PASI100 were 27.9/14.0 percent, 36.6/17.1 percent, 41.9/20.9 percent, 51.2/25.6 percent, 64.3/40.5 percent, and 57.1/34.3 percent, respectively. The proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and IGA 0 for JNJ-77242113 were 37.2/14.0 percent for 25mg QD, 46.3/19.5 percent 25mg BID, 60.5/23.3 percent for 50mg QD, 60.5/30.2 percent for 100mg QD, 73.8/42.9 for 100mg BID, and 65.7/31.4 percent for PBO to 100mg. Across treatment groups, 58.6 percent 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:

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

Efficacy and safety of a small molecule with innovative inhibition of TNFR1 signaling in plaque psoriasis: a double-blinded, randomized, placebo-controlled study

Presenters: Tiago R. Matos,^1,2 Markus Kohlmann,³ Mai Anh Nguyen,³ Ohn A. Chow,⁴ Anna Fishbein,⁵ Wagner Frank-Dietrich,⁶ Laurent Perrin,⁷ Nassr Nassr³

Affiliations: ¹Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; ²Sanofi, Amsterdam, Netherlands; ³Sanofi, Frankfurt, Germany; ⁴Sanofi, Cambridge, MA; ⁵Sanofi, Bridgewater, NJ; ⁶Charité Research Organisation, Berlin, Germany; ⁷Sanofi, Montpellier, France

Introduction: SAR441566 is an orally administrated small molecule that selectively inhibits tumor necrosis factor (TNF) signaling through the TNF receptor 1 (TNFR1). This proof-of-mechanism study in adults with mild-to-moderate plaque psoriasis evaluated the safety, tolerability, and clinical response of SAR441566 versus placebo through four weeks of treatment.

Methods: This Phase I, double-blind, placebo-controlled study enrolled male participants with chronic mild-to-moderate plaque psoriasis with at least two lesions of a Target Lesion Severity Score (TLSS) greater than 4 at baseline. Patients were randomized 2:1 to SAR441566 200mg twice a day (BID) or placebo for four weeks. Clinical efficacy was evaluated using the percent change from baseline to Week 4 in Psoriasis Area and Severity Index (PASI) and TLSS.

Results: A total of 38 male participants were randomized; 26 participants received oral SAR441566 and 12 received placebo. Baseline clinical characteristics were similar between the two groups. Patients who received SAR441566 had significant improvement from baseline in PASI versus placebo group at Week 2 (17.73% vs. 4.12%, p=0.005) and Week 4 (35.09% vs. 15.71%, p=0.009; p-value for one-sided test at 5% significance level) Consistent with these findings, patients who had received SAR441566 also had a significant improvement in TLSS versus placebo at Week 2 (17.06% vs. 6.29%, p=0.032) and Week 4 (38.18% vs. 20.44%, p=0.012). TLSS improved with SAR441566 irrespective of disease severity. Treatment with 200mg BID of SAR441566 over 28 days was safe and well tolerated, with no serious adverse events (AEs), severe treatment-emergent AEs, or AEs of special interest being reported.

Conclusion: SAR441566, a specific oral inhibitor of TNFR1 signaling, demonstrated clinical efficacy in mild-to-moderate psoriasis over a four-week treatment period. This novel oral therapy was safe and well tolerated. The results support the mechanism of action of SAR441566, a small molecule inhibitor of TNFR1 signaling, and warrants further clinical evaluation in psoriasis.

Acknowledgements: Research first presented at European Academy of Dermatology and Venereology (EADV), Berlin, Germany (October 11–14, 2023). Medical writing/editorial assistance was provided by Neha Upreti of Sanofi, according to the Good Publication Practice guideline. SAR441566 was identified in a research collaboration with UCB. This study (NCT05453942) was funded by Sanofi.

Funding/financial disclosures: TRM, MAN, NN, OAC, AF, MK, LP–Sanofi employees, may hold stock/stock options in the company. WFD–Charité Research Organisation, no conflicts of interest.

Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 52-week results from the SPROUT randomized controlled trial

Presenters: Loretta Fiorillo, MD;¹ Emily Becker, MD;² Susana Armesto, MD;³ Amy S. Paller, MD;⁴ Apostolos Kontzias, MD;⁵ Rajneet K. Oberoi, BPharm, PhD;⁵ Yuri Klyachkin, PhD;⁵ Hamid Amouzadeh, PhD;⁵ Zuoshun Zhang, PhD;⁵ Lisa Arkin, MD⁶

Affiliations: ¹Stollery Children’s Hospital University of Alberta, Edmonton, Alberta, Canada; ²Driscoll Children’s Hospital, Corpus Christi, TX; ³Hospital Universitario Marques de Valdecilla, Santander, Spain; ⁴Northwestern University Feinberg School of Medicine, Chicago, IL; ⁵Amgen Inc., Thousand Oaks, CA; 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. Apremilast, an oral phosphodiesterase 4 inhibitor approved for adult psoriasis, is being evaluated in pediatric moderate-to-severe psoriasis. The SPROUT trial evaluated the efficacy and safety of apremilast over 52 weeks in pediatric patients with moderate-to-severe psoriasis.

Methods: SPROUT (NCT03701763) was a Phase III, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6 to 17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age and randomized (2:1) to apremilast (weight-based, 20mg for ≥20–<50kg or 30mg for ≥50kg, twice per day) or placebo for 16 weeks, after which all patients continued to receive apremilast (APR/APR) or switched from placebo to apremilast (PBO/APR) through Week 52. At Week 16, primary (sPGA response: 33.1% vs. 11.5%) and major secondary (≥75% improvement in PASI [PASI75]: 45.4% vs. 16.1%) endpoints were met (p<0.0001).¹ Here, we report 52-week sPGA, PASI75, and safety results.

Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 221 (apremilast: 149 [91.4%]; placebo: 72 [87.8%]) completed the placebo-controlled period and 186 (APR/APR: 125 [76.7%]; PBO/APR: 61 [74.4%]) completed the 36-week extension. At Week 52, 56.3 percent of APR/APR patients achieved sPGA response and 71.4 percent achieved PASI75, demonstrating continued improvement from Weeks 16 through 52. PBO/APR patients also achieved sPGA response (52.5%) and PASI75 (75.4%) at Week 52. The safety profile was consistent with prior apremilast studies in adults. The most common treatment-emergent adverse events were gastrointestinal in nature and transient, resolving within 30 days. Apremilast pharmaco*kinetic profiles were similar regardless of 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:

1. Fiorillo L, Becker E, de Lucas R, et al. Efficacy and safety results of apremilast in pediatric patients with moderate to severe plaque psoriasis: 16-week results from SPROUT, a Phase III, randomized, controlled study. SKIN. 2023;7(2):s109.

Expected spesolimab plasma exposure following intravenous and subcutaneous dosing in patients with generalized pustular psoriasis

Presenters: Jason E. Hawkes,¹ Jason Guercio,² Sree Kurup,² Xiujiang Li,² Mark Lebwohl³

Affiliations: ¹Integrative Skin Science and Research, Pacific Skin Institute, Sacramento, CA; ²Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT; ³Icahn School of Medicine at Mount Sinai, New York, NY

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 two 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.

Conclusion: 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 versus SC dosing.

Reference:

1. Boehringer Ingelheim. Data on file: Modeling and simulation report: population pharmaco*kinetics and exposure-response of spesolimab in generalized pustular psoriasis. 2023; c41839684-01.

Four-weekly dosing intervals with subcutaneous spesolimab appear to be required for optimal prevention of generalized pustular psoriasis flares: data from the Effisayil 2 and Effisayil ON trials

Presenters: Diamant Thaçi,¹ Akimichi Morita,² Bruce Strober,³ Tiago Torres,⁴ Andreas Pinter,⁵ Angelo V. Marzano,⁶ James G. Krueger,⁷ Ming Tang,⁸ Patrick Hofmann,⁹ Christian Thoma,⁹ Mark G. Lebwohl¹⁰

Affiliations: ¹Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; ²Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ³Department of Dermatology, Yale University School of Medicine, New Haven, CT and Central Connecticut Dermatology Research, Cromwell, CT; ⁴Department of Dermatology, Centro Hospitalar Universitàrio de Santo António, University of Porto, Porto, Portugal; ⁵Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt am Main, Frankfurt am Main, Germany; ⁶Dermatology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; ⁷Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; ⁸Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai, China; ⁹Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; ¹⁰The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Generalized pustular psoriasis (GPP) is a rare chronic skin disease characterized by recurrent, acute, and often life-threatening flares of widespread neutrophilic sterile pustules and systemic inflammation. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor antibody, is approved for GPP flare treatment. In Effisayil 2, a randomized, placebo-controlled trial (NCT04399837), subcutaneous spesolimab was superior to placebo and well tolerated for flare prevention when administered as a 600mg subcutaneous loading dose followed by 300mg every four weeks (q4w) over 48 weeks. In Effisayil 2, three of 30 (10.0%) patients receiving subcutaneous spesolimab 300mg q4w had flares, and there were no flares after Week 4 until the end of the study.

Methods: We assessed the effect on flare recurrence of a longer (q12w) interval between subcutaneous spesolimab doses in Effisayil 2 and Effisayil ON (NCT03886246), an ongoing open-label extension trial. Flares were defined as a two-point or greater increase in GPP Physician Global Assessment total score with pustulation subscore of 2 or greater, or IV spesolimab or standard of care treatment due to GPP worsening.

Results: In Effisayil 2, nine of 31 (29.0%) patients who received subcutaneous spesolimab 300mg q12w had a flare; of those, seven (77.8%) experienced a flare before their second subcutaneous dose (Week 12), and five of seven (71.4%) flares occurred during Weeks 4 to 12, indicating the need for q4w dosing. In Effisayil ON, 36 of 108 (33.3%) patients who started q12w dosing were either escalated to a q4w regimen (n=24) or experienced a flare (n=12).

Conclusion: These observations suggest that subcutaneous spesolimab 300mg q4w is the optimal dosing regimen for prevention of GPP flares.

Low occurrence of predefined safety events across six randomized clinical trials of spesolimab in dermatologic conditions

Presenter: Kenneth B. Gordon,¹ Kilian Eyerich,² Milan J. Anadkat,³ Siew Eng Choon,⁴ Boni Elewski,⁵ Jonathan N. Barker,⁶ Arash Mostaghimi,⁷ Ming Tang,⁸ Thomas Haeufel,⁹ Christian Thoma,⁹ Diamant Thaçi¹⁰

Affiliations: ¹Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI; ²Department of Dermatology and Venerology, Medical Center, University of Freiburg, Germany; ³Washington University School of Medicine, Division of Dermatology, St. Louis, MO; ⁴Department of Dermatology, Hospital Sultanah Aminah Johor Bahru, Clinical School Johor Bahru, Monash University Malaysia, Subang Jaya, Malaysia; ⁵University of Alabama, Birmingham, AL; 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; 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 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.

Measuring GPPGA, pain, symptom, and quality of life index scores in untreated generalized pustular psoriasis: results from the placebo group of the Effisayil-2 trial

Presenters: Bruce Strober,¹ Arash Mostaghimi,² Milan J. Anadkat,³ Christian Thoma,⁴ Ming Tang,⁵ Jason R. Guercio,⁶ Mark G. Lebwohl,⁷

Affiliations: ¹Yale University School of Medicine, New Haven, CT; ²Brigham & Women’s Hospital, Harvard Medical School, Boston, MA; ³Washington University School of Medicine, St. Louis, MO; ⁴Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; ⁵Boehringer Ingelheim Investment Corporation Limited, Shanghai, People’s Republic of China; ⁶Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT; ⁷Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Generalized pustular psoriasis (GPP) is a chronic, inflammatory, and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report on the underlying disease burden of untreated GPP by longitudinally analyzing patients in the placebo group who did not experience a GPP flare.

Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. Patients were assessed for measures of chronic disease burden through the use of Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Total Score, Pain Visual Analog Scale (VAS), and Psoriasis Symptom Scale (PSS) at baseline and at four-week intervals during the trial, and Dermatology Life Quality Index (DLQI) at baseline and Weeks 4, 8, 12, 24, 36, and 48.

Results: Sixteen of 31 placebo-treated patients experienced a GPP flare over the 48-week observational period of the trial, defined as an increase in GPPGA score by 2 or greater from baseline and the pustular component of GPPGA 2 or greater. Of the remaining (“non-flaring”) 15 patients, 40 percent (6/15) had at least one GPPGA total score value of 2 (skin not clear or almost clear); four of six patients reported such score at four or more visits. Pain scores ranged from 0 to 92.47, with 47 (7/15) and 20 percent (3/15) of patients having at least one “moderate” and “severe” VAS score over 48 weeks, respectively. Most of the seven patients’ pain scores fluctuated with episodic peaks and valleys. Forty-seven (7/15) and 13 percent (2/15) of patients had at least one “moderate” and “severe” PSS score, respectively. “Moderate” and “very large” effect on quality of life was reported, at least once, in 67 (10/15) and 40 percent (6/15) of patients, respectively.

Conclusion: Acute flare was reported in more than 50 percent (16/31) of patients in the placebo group over 48 weeks. Despite not meeting the trial’s definition of GPP flare, most of the 15 “non-flaring” placebo-treated patients showed clear evidence of underlying GPP disease activity; nearly half did not have “clear” or “almost clear” skin and had moderate pain and symptoms, and a small subset reported severe pain and symptoms. The majority of patients experienced a moderate-to-very large impact on quality of life over the 48 weeks. These findings suggest that untreated GPP negatively affects patients even in the absence of acute flare events.

Roflumilast cream 0.3% in patients with psoriasis: improvement in pruritus and other patient reported outcomes from two pooled Phase III trials (DERMIS-1/DERMIS-2)

Presenters: Mark Lebwohl,¹ Chih-Ho Hong,² Leon Kircik,³ Jennifer Soung,⁴ Melinda Gooderham,⁵ Angela Moore,⁶ James Del Rosso,⁷ Irina Turchin,⁸ David Krupa,⁹ Robert Higham,⁹ David R. Berk⁹

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; 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, NY and Indiana Medical Center, Indianapolis, Physicians Skin Care, PLLC and Skin Sciences, PLLC, Louisville, KY; ⁴Southern California Dermatology, Santa Ana, CA; ⁵SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; ⁶Arlington Research Center, Arlington, TX and Baylor University Medical Center, Dallas, TX; ⁷JDR Dermatology Research Center, LLC, Las Vegas, NV and Advanced Dermatology and Cosmetic Surgery, Maitland, FL; ⁸Brunswick Dermatology Center, Fredericton, NB, Canada; ⁹Arcutis Biotherapeutics, Inc., Westlake Village, CA

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 or older. Pooled efficacy, safety, and tolerability from two identical, Phase III trials conducted in patients aged two years or older with plaque psoriasis affecting 2 to 20 percent body surface area (DERMIS-1 [NCT04211363] and DERMIS-2 [NCT04211389]) were previously reported. Significantly more roflumilast-treated patients achieved Investigator’s Global Assessment (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 versus vehicle-treated patients (–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.

Funding/financial disclosures: Sponsored by Arcutis Biotherapeutics, Inc.

VISIBLE Cohort B: guselkumab demonstrates significant scalp clearance at Week 16 in participants with moderate-to-severe scalp psoriasis across all skin tones

Presenters: A. Alexis,¹ A. McMichael,² T. Bhutani,³ A.O. Rodriguez,⁴ P. Grimes,⁵ C. Kindred,^6,7 G. Yadav,^8,9 J. Yeung,^9–11 O. Choi,¹² T. Alkousakis,¹² D. Chan,¹² K. Rowland,¹² J. Jeyarajah,¹³ L.-L. Gao,¹³ L. Park-Wyllie,¹⁴ S.R. Desai^15,16

Affiliations: ¹Weill Cornell Medicine, New York, NY; ²Wake Forest School of Medicine, Winston-Salem, NC; ³University of California San Francisco Medical Center, San Francisco, CA; ⁴Nashville Skin Comprehensive Dermatology Center, Nashville, TN; ⁵The Grimes Center for Medical and Aesthetic Dermatology; Vitiligo and Pigmentation Institute of Southern California, Los Angeles, CA; ⁶Kindred Hair & Skin Center, Columbia, MD; ⁷Howard University, Washington, DC; ⁸FACET Dermatology, Toronto, ON, Canada; ⁹Women’s College Hospital, Toronto, ON, Canada; ¹⁰Sunnybrook Health Sciences Centre, Toronto, ON, Canada; ¹¹Probity Medical Research, Waterloo, ON, Canada; ¹²Janssen Scientific Affairs, LLC, Horsham, PA; ¹³Janssen Research & Development, LLC, Spring House, PA; ¹⁴Janssen Inc., Toronto, ON, Canada; ¹⁵Innovative Dermatology, Plano, TX; ¹⁶University of Texas Southwestern Medical Center, Dallas, TX

Introduction: VISIBLE is an ongoing, first-of-its kind, Phase IIIb study of the efficacy and safety of guselkumab in patients of color across all skin tones. Here we present Week (W) 16 results of the VISIBLE Cohort B dedicated to moderate-to-severe scalp psoriasis.

Methods: VISIBLE Cohort B (n=108) participants were randomized 3:1 to receive guselkumab 100mg/placebo at W0 and W4, then every eight weeks. Co-primary endpoints were proportions of participants achieving scalp-specific Investigator’s Global Assessment (ss-IGA) response of absence of disease (0)/very mild disease (1) and Psoriasis Scalp Severity Index (PSSI) 90 response at W16. Major secondary endpoints were proportions of participants achieving complete scalp clearance (ss-IGA 0; PSSI100), median time to PSSI90 response, and mean percent improvements in PSSI and scalp surface area (SSA). The efficacy analysis population consisted of 102 participants correctly randomized to Cohort B. The safety population included 108 randomized participants.

Results: Participants were predominantly male (56.9%) with a median age of 43.5 years, mean weight of 88.1kg, and extensive moderate-to-severe scalp disease (mean SSA: 59.8%; mean PSSI: 34.3; 82.4% and 17.6% of participants with ss-IGA score of 3 and 4, respectively) at baseline. Less than 20 percent of participants had prior systemic therapy (phototherapy=11.8%; nonbiologic systemics=17.6%; biologics=12.7%). Significantly greater proportions of guselkumab-treated participants versus placebo-treated participants achieved ss-IGA 0/1 (68.4% vs. 11.5%; p<0.001), PSSI90 (65.8% vs. 3.8%; p<0.001; mean time to PSSI90: 11.6 weeks vs. not achieved), complete scalp clearance (ss-IGA 0: 57.9% vs. 3.8%; PSSI100: 59.2% vs. 3.8%; both p<0.001); and mean percent improvements in PSSI (87.6% vs. 37.8%) and SSA (86.6% vs. 33.4%; both p<0.001). Safety findings were consistent with the established guselkumab safety profile, with no new safety signals identified.

Conclusion: After just three doses of guselkumab, the majority of participants achieved rapid and significant scalp clearance across all measures evaluated, with nearly six of 10 achieving complete scalp clearance at W16. These results highlight that guselkumab is a highly effective treatment for extensive moderate-to-severe scalp psoriasis and will enable evidence-based shared decision-making for people with scalp psoriasis across diverse populations and the full range of skin tones.

Waiting to initiate apremilast: evidence of disease burden and topical cycling in mild-to-moderate psoriasis in real-world clinical practice

Presenters: Bruce Strober,^1,2 Linda Stein Gold,³ Paolo Gisondi,⁴ Kate Orroth,⁵ Myriam Cordey,⁵ Shia Kent,⁵ Cynthia Deignan,⁵ Shauna Jardon,⁵ Rohini K. Hernandez,⁵ M. Alan Brookhart,⁶ April Armstrong⁷

Affiliations: ¹Yale School of Medicine, CT; ²Central Connecticut Dermatology Research, CT; ³Henry Ford Health System, MI; ⁴University Hospital of Verona, Verona, Italy; ⁵Amgen Inc., Thousand Oaks, CA; ⁶Duke University, NC; ⁷University of California Los Angeles, CA

Introduction: The IPC recommends systemic therapy based on affected body surface area (BSA), special area involvement, or topical treatment failure. Apremilast is an oral phosphodiesterase 4 inhibitor approved to treat psoriasis. In the ADVANCE study, patients with limited skin disease (mean BSA: 6.4%) experienced high quality-of-life impairment (mean Dermatology Life Quality Index [DLQI] score: 9.9). Given the cumulative life impairment of psoriasis and impact of delaying systemic treatment, we explored early initiation (EI) versus late initiation (LI) of apremilast in patients with limited skin involvement. We defined time-to-initiation, assessed factors associated with earlier apremilast initiation, determined characteristics of apremilast initiators, and evaluated disease burden before apremilast initiation.

Methods: This retrospective observational analysis of the OM1 database included conventional synthetic disease-modifying antirheumatic drug-naïve adults with psoriasis and subsequent BSA value (≥1% and ≤10%; index date), apremilast initiation in the United States between 2014 to 2022 at/after the index date, no other systemic psoriasis medications at initiation, no evidence of psoriatic arthritis, and 365 days or more of baseline data. Disease burden was assessed by topical use and BSA. A multivariable Cox proportional hazards model estimated predictors of earlier apremilast treatment.

Results: Among 3,589 patients (mean age: 52 years), time (mean/median) between initial psoriasis diagnosis to first available BSA was 366/45 days; 22 percent of patients had BSA 1 to less than 3 percent, and 78 percent had BSA 3 to 10 percent. EI was defined as six months or less based on typical frequency of dermatology visits and time-to-initiation (median: 4 months). Of apremilast initiators, 58 percent had EI and 42 percent had LI (>6 months). Baseline factors associated with earlier apremilast initiation included 3 to 10 percent BSA at index date (hazard ratio [HR]: 2.14 [95% confidence interval: 1.82, 2.51]) and three or more prior topical treatments within the baseline period (HR: 1.38 [1.15, 1.65]). Men and patients aged 65 years or older were less likely to initiate early (HR: 0.85 [0.75, 0.98] and 0.49 [0.38, 0.63], respectively). Median time-to-initiation for EI was two weeks versus 16 months for LI. Increase in BSA from baseline to apremilast initiation was 52.1 percent in LI versus 3.4 percent in EI. Notably, 45.9 percent versus 30.4 percent of LI versus EI patients had three or more prior topicals, with 6.9 percent of LI patients versus 1.5 percent of EI patients experiencing 10 or more topicals. Greater topical cycling in LI versus EI was also observed in patients with apremilast monotherapy.

Conclusion: Late initiators waited about 16 months to initiate apremilast, during which BSA increased by 52.1 percent. Physicians tended to wait until patients had higher BSAs before initiating apremilast, even with EI. Additionally, late initiators had more topical cycling versus early, with 6.9 percent experiencing 10 or more topicals versus 1.5 percent for EI. This suggests real-world patients with psoriasis may experience exacerbated disease burden waiting to initiate systemic treatment.

Seborrheic Dermatitis

Roflumilast foam 0.3% once daily in patients with seborrheic dermatitis: improvement in pruritus and other patient reported outcomes from a Phase III trial (STRATUM)

Presenters: Neal Bhatia,¹ Fran Cook-Bolden,² Janet DuBois,³ Laura Ferris,⁴ Linda Stein Gold,⁵ Irina Turchin,⁶ Matthew Zirwas,⁷ David Krupa,⁸ Patrick Burnett,⁸ David R. Berk,⁸ David H. Chu⁸

Affiliations: ¹Therapeutics Clinical Research, San Diego, CA; ²Park South Medical, Bronx, NY; ³DermResearch, Inc., Austin, TX; ⁴University of Pittsburgh, Department of Dermatology, Pittsburgh, PA; ⁵Henry Ford Medical Center, Detroit, MI; ⁶Brunswick Dermatology Center, Fredericton, NB, Canada; ⁷Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH; ⁸Arcutis Biotherapeutics, Inc., Westlake Village, CA

Introduction: Roflumilast is a nonsteroidal, highly potent phosphodiesterase 4 inhibitor developed as a once-daily cream and foam formulations being studied in patients for long-term treatment of atopic dermatitis and seborrheic dermatitis (SD). Efficacy and safety of once-daily roflumilast foam 0.3% in patients aged nine years or older with at least moderate SD from this Phase III 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, Dermatology Life Quality Index (DLQI)/Children’s DLQI (CDLQI), and local tolerability.

Results: Among patients with baseline WI-NRS score of 2 or greater, more roflumilast-treated than vehicle-treated patients achieved WI-NRS score 0/1 at Week 8 (70.7% vs. 52.9%; p=0.0085), with improvements in itch compared to vehicle occurring 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/financial disclosures: Sponsored by Arcutis Biotherapeutics, Inc.