2-grade Improvement Research Articles

Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis.

Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator's Global Assessment or Evaluator's Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: - 11.5; 95% confidence interval [CI]: - 14.39, - 8.62), NILC (MD: - 12.25; 95% CI: - 15.21, - 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: - 12.8, - 11.2, and - 10.1, respectively), NILC (MD: - 11.6, - 13.9, and - 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions.

"Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Platysma Prominence: A Randomized Phase 2 Dose-Ranging Study".

With aging, repetitive contraction of the platysma leads to an increase in platysma prominence (PP) characterized by the accentuation of vertical neck bands and blunting of the jawline's contour. This multicenter, double-blind, phase 2 study evaluated onabotulinumtoxinA (onabotA) treatment in adults with Moderate to Severe PP. Participants were randomized to receive 1 treatment of onabotA low dose (LD), onabotA high dose (HD), or placebo, and were followed for 4 months. Efficacy endpoints were the achievement of a ≥ 1-grade improvement on both the left and right sides at Day 14 at maximum contraction as assessed by the investigator (primary) or by participants (secondary) using validated scales. Safety was evaluated throughout. Participants in the modified intent-to-treat population (N = 164) had a mean age of 50 years; 95.1% were female and 93.9% were White. The primary endpoint was met for both onabotA groups, with investigator-assessed ≥ 1-grade improvement in 77.8% (LD) and 88.2% (HD) vs 12.0% (placebo) of participants on Day 14 (P < 0.0001 vs placebo). Based on participant self-assessment, 75.9% (LD) and 88.2% (HD) vs 18.0% (placebo) achieved ≥ 1-grade improvement on Day 14 (P < 0.0001 vs placebo). Most treatment-related adverse events (AEs) were procedure-related, transient, and mild in severity. The most frequent onabotA-related AE was neck muscle weakness, reported in the HD group. OnabotA was effective in improving the appearance of PP based on both investigators' and participants' ratings. Treatment was well tolerated.

The gold protocol: A combined treatment approach for neck rejuvenation with calcium hydroxyapatite, botulinum toxin, and hyaluronic acid in the same session.

The signs of aging seem to be more visible on the neck compared to other locations, especially if a patient has already gone through facial rejuvenation procedures. Treatment of the aging neck imposes a challenge to the clinician, since one single approach is usually not enough to achieve the desired result, requiring multiple injections and sessions, which apart from being painful for the patients, is time-consuming for the clinician. To describe the use of calcium hydroxyapatite, incobotulinum toxin type A and Cohesive poly-densified matrix hyaluronic acid diluted in the same syringe and injected in the same session for neck rejuvenation. Fifteen women, older than 18 years, with cervical skin flaccidity grade 1-4 in a previously validated 5-point rating scale (Dermatologic Surg, 2016; 42, S94), who sought neck rejuvenation were injected in this pilot study with a single session with a combined hybrid mixture of calcium hydroxyapatite, incobotulinum toxin type A, and Cohesive poly-densified matrix hyaluronic acid and followed up for 90-180 days. At the 4-month post injection evaluation, 93.3% of the patients presented at least 1-grade improvement in the 5-point scale as evaluated by the investigator. No serious adverse events were reported, being most mild and transient in nature. CaHA, incoBonTA, and CPM-HA have complementary mechanisms of action and may be injected from the same syringe in the same session, boosting the final outcome, with high patient satisfaction, and ease of process for both patients and clinicians.

Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).&#x0D; Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.&#x0D; Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p&lt;0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001). Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p&lt;0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p&lt;0.001).&#x0D; Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.

Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis: Individual Patient PASI and PASI-HD Responses: Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Background: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. Pooled efficacy and safety results from two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) have been presented previously. The Psoriasis Area and Severity Index (PASI) is used to assess the severity of plaque psoriasis in clinical trials; however, PASI is not precise when the area of involvement is &lt;10% of a given anatomic region. A modified version of the PASI, the PASI-high discrimination (PASI-HD), allows more precise assessment of psoriasis in body regions where &lt;10% area is affected. We present individual patient responses using PASI and PASI-HD.&#x0D; Methods: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. PASI and PASI-HD were used to measure disease severity; individual patient PASI and PASI-HD responses were plotted graphically. Safety and tolerability were also evaluated and were reported previously.&#x0D; Results: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). Likewise, statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving 50% reduction in PASI-HD (79.4% vs. 33.1%; P&lt;0.0001), 75% reduction (59.9% vs. 17.9%, P&lt;0.0001), 90% reduction (39.9% vs 9.1%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.0001). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable to vehicle. At the first application of roflumilast cream 0.3% (day 1), 96% of patients reported no or mild sensation, increasing to 99% of patients at Weeks 4 and 8.&#x0D; Conclusions: Roflumilast cream 0.3% provided greater improvement in IGA Success, PASI, and PASI-HD versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials. PASI-HD provided higher discrimination of effects of treatment in areas with &lt;10% involvement than the traditional PASI.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389&#x0D; Financial Disclosures: Arcutis Biotherapeutics, Inc.

Tapinarof Cream 1% Once Daily is Efficacious in the Treatment of Mild to Severe Plaque Psoriasis in the Head and Neck Region

Introduction: Tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults, with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) was efficacious and well tolerated for treating psoriasis, including the head and neck region. However, efficacy data specific to scalp treatment were not captured.Objective: To assess efficacy, safety, and tolerability of tapinarof cream for the treatment of adults with plaque psoriasis affecting the head and neck region, including the scalp. Methods: In this phase 4, open-label trial, adults received tapinarof for 12 weeks. Patients had plaque psoriasis affecting the head and neck (stable for ≥3 months), and a target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe). The primary endpoint was the proportion achieving a tPGA response (tPGA score of clear [0], or almost clear [1] and ≥2-grade improvement from baseline at Week 12). Additional endpoints included time to achieve tPGA response; proportion with complete clearance (tPGA score=0); and with ≥75% and ≥90% improvement in Psoriasis Area and Severity Index score (PASI; head and neck region). Safety and tolerability evaluations included adverse events (AEs) and investigator-assessed Local Tolerability Scale (LTS) scores. Results: 31 patients with mild to severe plaque psoriasis affecting the head and neck region received tapinarof. At baseline, 54.8% had a tPGA score of 3 and 58.1% (18/31) had the target lesion on the scalp. At Week 12, 88.5% (n=23/26) achieved a tPGA response and 80.8% (n=21/26) achieved complete clearance (tPGA=0). There was rapid onset of efficacy, with both tPGA response and complete clearance achieved as early as Week 1, the first assessment, in some patients. Median times to tPGA response and complete clearance were ~4 and 8 weeks, respectively. At Week 12, 96.2% (n=25/26) and 84.6% (n=22/26) achieved a ≥75% and ≥90% improvement in PASI (head and neck region), respectively. Most AEs were mild or moderate, consistent with previous trials; the most frequent were contact dermatitis, folliculitis, and headache. Most patients had no irritation of the head and neck region (LTS score=0) at all visits.Conclusions: Tapinarof cream 1% QD demonstrated rapid onset of clinically meaningful efficacy as early as Week 1 in patients with plaque psoriasis affecting the head and neck region, including for scalp lesions. Tapinarof cream is a cosmetically elegant, well-tolerated, non-steroidal treatment option in adults with mild to severe plaque psoriasis, including in the head and neck region.Funding Support: Dermavant Sciences, Inc.

Association Between Early Clinical Responses and Long-Term Outcomes With Ruxolitinib Cream Treatment in Mild to Moderate Atopic Dermatitis

In the TRuE-AD1/2 studies, patients aged ≥12 years with atopic dermatitis (Investigator’s Global Assessment [IGA] 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75%/1.5% ruxolitinib cream or vehicle for an 8-week, double-blind period followed by a 44-week long-term safety (LTS) period of as-needed ruxolitinib cream. This analysis examines associations between Week 8 responder status to 1.5% ruxolitinib cream with LTS outcomes. At Week 8, 57.0% (244/428) of LTS-evaluable patients applying 1.5% ruxolitinib cream achieved IGA–Treatment Success (IGA-TS; IGA 0/1 with ≥2-grade improvement from baseline); 66.6% (285/428) achieved ≥75% improvement in Eczema Area and Severity Index from baseline (EASI-75); 45.8% (196/428) achieved Itch numerical rating scale 0/1 (NRS 0/1). For patients with ≥2 visits (every 4 weeks) during LTS, mean percentages of visits with clear/almost clear skin were 83.2% vs 59.7%, 82.2% vs 54.9%, and 77.3% vs 70.1% for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Mean percentages of visits with clear/almost clear skin were similar regardless of time to achieve IGA-TS (83.4%/77.4%/81.9% for those achieving at Week 2/4/8), EASI-75 (80.7%/78.8%/81.6%), and Itch NRS 0/1 (75.8%/70.7%/72.8%). During LTS, mean (SD) cumulative treatment-free days due to complete clearance were 149.2 (86.43) vs 104.0 (89.10), 146.4 (88.43) vs 95.9 (83.55), and 142.6 (87.58) vs 124.4 (91.47) for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Percentage of treatment-free days between study visits (between Weeks 8 and 12 vs Weeks 48 and 52) among Week 8 responders and nonresponders increased from 44.1% to 50.2% and from 16.3% to 42.3% for IGA-TS; from 41.2% to 49.9% and from 14.9% to 40.6% for EASI-75; from 39.8% to 49.4% and from 29.9% to 46.0% for itch NRS 0/1. In summary, efficacy responses achieved with 8-week ruxolitinib cream treatment are associated with higher disease control in LTS; however, nonresponders approach similar disease control with continued treatment. As-needed ruxolitinib cream monotherapy demonstrated substantial long-term disease control regardless of time to first response achievement.

Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (− 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60–80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).

514 - Tapinarof cream 1% once daily: significant efficacy in the treatment of atopic dermatitis in two pivotal phase 3 trials in adults and children down to 2 years of age

Abstract Introduction Tapinarof cream 1% once daily (QD) demonstrated efficacy versus vehicle and was well tolerated in adults and adolescents with moderate to severe atopic dermatitis (AD) in a previously reported phase 2 trial. Objective Here, we report pivotal phase 3 efficacy and safety results for tapinarof cream 1% QD in the treatment of adults and children down to 2 years of age with AD. Materials and Methods ADORING 1 and 2 were two identical phase 3, randomized, double-blind, vehicle-controlled trials. Eligibility criteria included a Validated Investigator Global Assessment for Atopic DermatitisTM (vIGA-ADTM) score of ≥3, Eczema Area and Severity Index (EASI) score of ≥6, and body surface area (BSA) involvement of 5–35%. Patients were randomized 2:1 to receive tapinarof cream 1% or vehicle cream QD for 8 weeks. The primary efficacy endpoint was vIGA-ADTM response, defined as a score of clear (0) or almost clear (1) and ≥2-grade improvement from baseline at Week 8. Secondary efficacy endpoints included ≥75% improvement in EASI score (EASI75) and proportion of patients (aged ≥12 years) with a baseline Peak Pruritus-Numerical Rating Scale (PP-NRS) score of ≥4 who achieved a ≥4-point reduction at Week 8. Adverse events (AEs) included rates of AEs of special interest (AESIs): contact dermatitis, follicular event, and headache. Results 407 and 406 patients aged 2–81 years were randomized in ADORING 1 and 2, respectively. At baseline, 84.0–89.9% of patients had a vIGA-ADTM score of 3 (moderate), mean EASI score of 12.5–13.3, and mean BSA affected of 16.7–16.9% across trials. At Week 8, both the primary and all secondary efficacy endpoints were met with statistical significance in the tapinarof groups versus vehicle: vIGA-ADTM response rates were 45.4% vs 13.9% and 46.4% vs 18.0% (both P&amp;lt;0.0001); EASI75 response rates were 55.8% vs 22.9% and 59.1% vs 21.2% (both P&amp;lt;0.0001); and a ≥4-point reduction in PP-NRS was achieved by 55.8% vs 34.2% (P=0.0366) and 52.8% vs 24.1% (P=0.0015), in ADORING 1 and 2, respectively. AEs were mostly mild or moderate; the most frequent (≥5% in any group) were folliculitis, headache, and nasopharyngitis. Trial discontinuation rates due to AEs were lower with tapinarof versus vehicle (ADORING 1: 1.9% vs 3.6%; ADORING 2: 1.5% vs 3.0%, respectively). Rates of AESIs with tapinarof versus vehicle were: contact dermatitis 1.5% vs 2.2% and 1.1% vs 1.5%; follicular events 10.0% vs 0.7% and 8.9% vs 1.5%; and headache 7.0% vs 2.2% and 1.5% vs 0%, in each trial, respectively. Conclusions Tapinarof cream 1% QD demonstrated statistically significant efficacy compared with vehicle for primary and secondary efficacy endpoints in adults and children down to 2 years of age with AD. Tapinarof was well tolerated, with no new safety or tolerability signals. AEs were mostly mild to moderate and led to low rates of trial discontinuation, demonstrating the predictable safety profile of tapinarof cream 1% QD.

522 - Efficacy and safety of abrocitinib in combination with topical therapy in adolescents from China with moderate-to-severe atopic dermatitis: A post hoc analysis of the JADE TEEN phase 3 trial

Abstract Background Atopic dermatitis (AD) has a reported prevalence of 3% in adolescents aged 13-14 years in China. However, studies evaluating the efficacy and safety of Janus kinase 1-selective inhibitors in AD in patients from China are limited. Abrocitinib is an oral, once-daily, Janus kinase 1–selective inhibitor approved for the treatment of moderate-to-severe AD in adults and adolescents in the United States and in adults in China. The efficacy of abrocitinib as monotherapy or in combination with medicated topical therapy has been demonstrated in multiple phase 3 clinical trials in adolescent and adult patients with moderate-to-severe AD. In a separate phase 3 trial of adolescent patients (JADE TEEN [NCT03796676]), abrocitinib administered in combination with medicated topical therapy was effective in improving the signs and symptoms of moderate-to-severe AD, with an acceptable safety profile. JADE TEEN was conducted in several countries, including China. Objective To assess the efficacy and safety of abrocitinib in combination with topical therapy in Chinese adolescents with moderate-to-severe AD enrolled in JADE TEEN. Methods In JADE TEEN, adolescent patients (aged 12 to 17 years) were randomly assigned (1:1:1) to receive abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks in combination with medicated topical therapy. This post hoc analysis included data from patients enrolled in JADE TEEN from mainland China. Assessments included the proportion of patients at week 12 who achieved an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75), and ≥4 point improvement from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi). Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score at week 12 was also assessed. Safety was assessed by treatment emergent adverse event (TEAE) monitoring. Results Of 285 patients enrolled in JADE TEEN, 52 (18.2%) were enrolled from mainland China and consisted of 14, 18, and 20 patients who were randomly assigned to receive abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Median age at baseline was 15.0 years (interquartile range [IQR], 14.0-17.0 years), and median duration since onset of AD was 9.8 (IQR, 4.4-13.7) years. At week 12, a higher proportion of patients treated with abrocitinib at either dose compared with placebo achieved efficacy responses of IGA 0/1 (abrocitinib 200 mg, 46.2%; abrocitinib 100 mg, 46.7%; placebo, 22.2%), EASI-75 (69.2%; 73.3%; 27.8%), and PP-NRS4 (63.6%; 50.0%; 20.0%). Decreases from baseline in PSAAD total score were greater in patients treated with abrocitinib at either dose compared to placebo at week 12 (abrocitinib 200 mg, −3.4; abrocitinib 100 mg, −3.2; placebo, −1.8). Response rates were largely comparable between patients from China and the overall JADE TEEN study population, although CIs were wider in the China subgroup because of the small sample size. In the China subgroup, TEAEs were experienced by 13 (92.9%), 16 (88.9%), and 15 (75.0%) patients in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, respectively. Compared to the overall population, there were no new safety signals identified in patients from China. Conclusions Abrocitinib administered in combination with medicated topical therapy was effective and well tolerated in adolescent patients from China with moderate-to-severe AD. Efficacy and safety findings were consistent with the overall JADE TEEN population.

505 - Once-daily roflumilast cream 0.15% for atopic dermatitis: pooled results from INTEGUMENT-1/2 phase 3 trials

Abstract Introduction Roflumilast cream 0.15% is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily treatment for atopic dermatitis (AD). Objectives Here, pooled results from two identical Phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587 and INTEGUMENT-2: NCT04773600) are presented. Methods Patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of Mild or Moderate were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) once daily for 4 weeks. Results A significantly greater percentage of roflumilast- versus vehicle-treated patients achieved the primary endpoint, vIGA-AD Success (Clear or Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4 (31.3% vs. 14.1%; P&amp;lt;0.0001). Significant differences favoring roflumilast were observed for multiple secondary endpoints at Week 4: percentage of patients achieving vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P&amp;lt;0.0001), percentage achieving 75% reduction in EASI (42.7% vs. 20.6%; P&amp;lt;0.0001), and percentage with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction (31.9% vs. 16.6%; P&amp;lt;0.0001). Improvement in itch was reported as early as 24 hours. Both groups had low incidences of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation. Local tolerability was favorable, with &amp;gt;90% of patients reporting no or mild sensation across both treatment groups at all timepoints. Conclusions Once-daily roflumilast cream 0.15% provided improvement across multiple efficacy endpoints by Week 4 with favorable safety and tolerability in patients aged ≥6 years with AD in two Phase 3 trials.

Lower Gluteal Liposuction Combined With Upper Gluteal and Infragluteal Region Fat Grafting: A Novel Concept to Improve Gluteal Ptosis.

Gluteal ptosis results in a severe disturbance of gluteal aesthetics. Currently, satisfactory procedures for improving gluteal ptosis are lacking. To improve gluteal ptosis, the authors propose a novel concept of combined liposuction of the lower gluteal region and fat grafting to the upper gluteal and infragluteal regions, and verify its efficacy and safety. Patients who underwent liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions between January 2020 and July 2023 were retrospectively reviewed. Postoperative changes in the gluteal ptosis grade, complications, and patient satisfaction were evaluated. A total of 28 patients were enrolled in this study; 21 (75.0%) patients had gluteal ptosis grade 4 and 7 (25.0%) patients had gluteal ptosis grade 5. The median fat removal volume was 210 mL, and the median fat graft injected volume was 355 mL in the gluteal region and 180 mL in the infragluteal region. All patients showed improvement in gluteal ptosis; 16 (57.1%) patients improved by 1 grade and 12 (42.9%) patients showed a 2-grade improvement. All patients were satisfied with their posttreatment outcomes. Only 1 patient showed lateral translocation of the fat graft. No other complications were observed. Liposuction of the lower gluteal region combined with fat grafting to the upper gluteal and infragluteal regions is effective in improving gluteal ptosis, with a low risk of complications and high patient satisfaction.

Roflumilast Cream 0.3% in Patients with Chronic Plaque Psoriasis: Individual Patient Response from the Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Roflumilast cream 0.3% in patients with chronic plaque psoriasis: individual patient response from the pooled DERMIS-1 and DERMIS-2 phase 3 trials&#x0D; &#x0D; James Del Rosso1 on behalf of the authors&#x0D; &#x0D; INTRODUCTION: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. The efficacy and safety of the pooled results of two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) in patients aged ≥2 years with plaque psoriasis have been previously presented. We present individual patient responses using the Psoriasis Area and Severity Index (PASI).&#x0D; METHODS: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% of body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8; IGA of Clear or Almost Clear was a secondary endpoint. PASI was used to measure disease severity; individual patient PASI responses were plotted graphically. Safety and tolerability were also evaluated and have been previously reported.&#x0D; RESULTS: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001) and IGA of Clear or Almost Clear (48.0% vs. 9.5%; nominal P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). At the first post-treatment timepoint evaluated (Week 2), 85.7% of roflumilast-treated patients had a measurable improvement in PASI, increasing to 95.0% by the last timepoint (Week 8). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. Approximately 96% of patients reported no or mild sensation after the first application of roflumilast cream 0.3%, improving to more than 99% of patients at Week 4 and Week 8, similar to vehicle.&#x0D; CONCLUSIONS: Roflumilast cream 0.3% provided greater improvement in IGA Success, IGA of Clear or Almost Clear, and PASI versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials.&#x0D; Sponsored by Arcutis Biotherapeutics, Inc.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389

Application and Comparison of Dermoscopy and Reflectance Confocal Microscopy in the Target Treatment of Genital Lichen Sclerosus: A Single-Arm Prospective Study.

The treatment of genital lichen sclerosus (GLS) remains challenging. Baricitinib has been introduced in the treatment of GLS, but there's no imaging evaluation for GLS patients treated with it. No comparison of dermoscopy and reflectance confocal microscopy (RCM) assessments in GLS has been conducted. We performed this study to evaluate the efficacy and safety of baricitinib for GLS and to compare the value of dermoscopy and RCM assessments in GLS. Participants were treated with baricitinib for 6months and assessed at week 0, 2, 4, 6, 8, and every 4weeks for the next 16weeks. All patients were evaluated for clinical, dermoscopic, and RCM variables, with numeric scores assigned to each parameter. Twenty-six GLS patients were included in this study. All patients achieved Investigator's Global Assessment score ≤ 1 (with ≥ 2-grade improvement) at week 20. The scores of pruritus and pain decreased since week 2 (both P < 0.05). The DLQI and VQLI scores significantly decreased since week 4 (both P < 0.0001). White structureless areas improved at week 2 and white shiny streaks and follicular plugs improved at week 4 under dermoscopic examination. Vessels (P < 0.001) and brown structureless areas (P = 0.003) increased at week 8. In RCM, inflammatory cells count significantly decreased at week 2 (100.03 ± 33.24, P < 0.0001), with substantial regression at week 8 (16.98 ± 5.54, P < 0.0001). Epidermal thickness increased at week 12 (157.44 ± 37.87μm versus 134.13 ± 36.60μm, P = 0.0284). Irregular papillae, spongiosis, and fiber structures improved at week 20, week 4, and week 6 (all P < 0.01). Transient hypercholesterolemia (11.54%), thrombocytosis (7.69%), and elevated alanine aminotransferase (7.69%) occurred during treatment. Both dermoscopy and RCM can be useful and non-invasive adjuvant tools for the evaluation and therapeutic monitoring of GLS. We recommended white structureless areas under dermoscopy and inflammatory cells count under RCM as variables for dermatologic imaging evaluation for GLS. Baricitinib is effective and safe for GLS, while randomized controlled trials are warranted.

Roflumilast (Zoryve)

&#x0D; CADTH recommends that Zoryve be reimbursed by public drug plans for the treatment of plaque psoriasis, including treatment of psoriasis in the intertriginous areas, in patients 12 years of age and older if certain conditions are met.&#x0D; Zoryve should only be covered to treat patients who have a clinical diagnosis of plaque psoriasis with an Investigator Global Assessment (IGA) score of at least 2 (mild) and an area of plaque psoriasis appropriate for topical treatment covering a body surface area of 2% to 20% (inclusive).&#x0D; Zoryve should be discontinued if a response has not been demonstrated by 8 weeks. A response to treatment is defined as at least a 2-grade improvement from baseline in IGA score or an IGA score of “clear” or “almost clear” (0 or 1). The cost of Zoryve should not exceed the drug program cost of treatment with the least costly topical therapy reimbursed for the treatment of plaque psoriasis.&#x0D;

Self-perception of natural outcome, appearance, and emotional well-being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender.

OnabotulinumtoxinA (onabotA) is indicated for upper facial lines (UFL). Fear of unnatural-looking outcomes is a frequently reported treatment barrier. Examine patient-reported outcomes (PROs) after onabotA treatment for UFL. A post hoc analysis was conducted on two 12-month pivotal studies of onabotA for forehead and glabellar lines (20 U each), with/without treatment of crow's feet lines (±24 U). This analysis used PROs from the Facial Line Satisfaction Questionnaire: Items 4 (natural look), 5 (treatment effect), 11 (met expectations), and Impact Domain (appearance and psychological impact). The analysis included 458 neurotoxin-naive adults achieving a ≥2-grade improvement in forehead line (FHL) severity on the Facial Wrinkle Scale at Day 30 (primary endpoint). [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'forehead line (FHL)' in this version.] Data were further stratified into millennials and men. At Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self-perceived appearance and psychological well-being, but millennials had higher, and men had lower odds of reporting these improvements. Participants achieving a ≥2-grade improvement in FHL severity after onabotA reported high satisfaction with natural outcomes and the treatment effect, with improved self-perceived appearance and psychological well-being. [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'FHL' in this version.] These results may help aesthetic providers and patients address fears regarding unnatural results with onabotA.

Scalp, eyebrow, and eyelash hair regrowth with continued ritlecitinib treatment among patients with alopecia areata without target efficacy response at Week 24: post hoc analysis of the ALLEGRO phase 2b/3 study

Background: This post hoc analysis of the ALLEGRO phase 2b/3 study (NCT03732807) assessed response to ritlecitinib, an oral JAK3/TEC family kinase inhibitor, between Weeks 28-48 among patients with alopecia areata (AA) who did not meet target efficacy response criteria at Week 24.&#x0D; Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss received daily ritlecitinib 10 mg (included for dose ranging only), 30 or 50 mg (±4-week 200-mg daily loading dose), or placebo for 24 weeks. After Week 24, ritlecitinib groups continued their assigned doses and the placebo group switched to ritlecitinib 200/50 or 50 mg through Week 48. This analysis included patients receiving ritlecitinib 30 or 50 mg (±4-week 200-mg daily loading dose) who had not responded at Week 24, based on Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair), SALT score ≤10, or eyebrow (EBA) or eyelash (ELA) assessment (normal or ≥2-grade improvement from baseline among patients with abnormal EBA or ELA score at baseline), and followed them through Week 48.&#x0D; Results: Of the patients in the ritlecitinib groups who did not meet SALT ≤20 response at Week 24, 5-8% had response at Week 28, with rates increasing to 22-34% at Week 48. A similar trend was observed for SALT ≤10 (6-12% and 20-25%), EBA (8-14% and 20-33%), and ELA (4-15% and 17-30%) at Weeks 28 and 48, respectively, for patients not achieving the respective response at Week 24. Ritlecitinib was well tolerated through Week 48. Most common adverse events were upper respiratory tract infection, nasopharyngitis, and headache.&#x0D; Conclusion: Patients with AA treated with ritlecitinib who don’t meet target efficacy response at Week 24 may achieve response at later time points with continued ritlecitinib treatment.

Improvement in Epiphora Using TEARS Grading Following Surgical Treatment of Meibomian Gland Inversion in Patients With Facial Nerve Palsy.

To assess epiphora outcomes using the TEARS grading score in patients with concomitant meibomian gland inversion (MGI) and facial nerve palsy (FNP) undergoing correction of MGI. Retrospective, 5-year, noncomparative, single-center study of patients with MGI and FNP, treated with MGI correction, under the supervision of a single surgeon. A validated "TEAR" score was used to assess changes in epiphora. Ten patients with FNP, MGI, and epiphora were analyzed from a group of 160 patients with FNP who underwent MGI surgery between 2017 and 2022. The mean age at surgery was 50 years (range, 13-76 years). T, E, and A scores significantly improved (p < 0.05). Eighty percent of patients saw a reduction in tearing frequency (T), with 60% gaining ≥ 2-grade improvement. Improvements in clinical effects (E) and activity limitation (A) were seen in 80% of patients, with 40% and 50% gaining ≥ 2-grade improvement, respectively. R scores (related to reflex tearing) improved by 60%, with 40% seeing ≥ 2-grade improvement. Nine patients (90%) improved symptomatically with an average improvement "S" score of 65% over a mean follow-up period of 30 months. All patients demonstrated restoration of the normal anatomical position of the meibomian glands. MGI can cause epiphora in patients with FNP and may explain cases where symptoms persist despite standard surgical intervention. This study provides proof of concept that MGI correction can improve epiphora and that identifying MGI may be considered a critical step in the treatment algorithm for epiphora in patients with FNP.

390 Efficacy and safety of roflumilast cream 0.15% in adults and children aged ≥6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2)

Abstract Roflumilast is a selective, highly potent phosphodie­sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P &amp;lt; 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P &amp;lt; 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P &amp;lt; 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P &amp;lt; 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with &amp;gt;90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials.

434 Efficacy and safety of crisaborole ointment, 2%, in Chinese and Japanese pediatric patients aged 2–17 years with mild-to-moderate atopic dermatitis

Abstract Atopic dermatitis (AD) is a common, chronic immuno-inflammatory skin disorder that commonly arises during childhood. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. This study aims to evaluate the efficacy and safety of crisaborole ointment, 2%, in pediatric Chinese and Japanese patients aged 2–17 years with mild-to-moderate AD. This post hoc analysis of a double-blind, vehicle-controlled, phase 3 study (CrisADe CLEAR; NCT04360187) evaluated the safety and efficacy of crisaborole in Chinese and Japanese patients aged ≥2 years with mild-to-moderate AD (involving ≥5% treatable body surface area). Patients were randomly assigned 2 : 1 to receive crisaborole or vehicle, respectively, twice-daily for 28 days. In this analysis, subgroups consisting of Chinese and Japanese patients aged 2–6 years, 2–11 years, and 12–17 years from the overall population were assessed. Efficacy endpoints included percent change from baseline in Eczema Area and Severity Index (EASI) total score at Day 29, improvement in Investigator’s Static Global Assessment (ISGA) score [score of 0 (clear) or 1 (almost clear)] at Day 29, success per ISGA (score of 0 or 1 with a ≥2-grade improvement from baseline) at Day 29, and change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS; used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi) score at Week 4 (patients ≥12 years only). Safety was also assessed. Of 391 patients in the overall study, 93 were aged 2–6 years, 99 were aged 7–11 years, and 40 were aged 12–17 years. A greater reduction in percent change from baseline in EASI total score at Day 29 was shown in crisaborole- vs. vehicle-treated patients for patients aged 2–6 years and the overall population, with comparable reductions in other age subgroups (ClinicalTrials.gov, NCT04360187). Patients in the crisaborole group vs. the vehicle group had higher rates of ISGA improvement (age 2–6 subgroup) and success per ISGA (age 12–17 subgroup); comparable response rates were seen in other age subgroups (ClinicalTrials.gov, NCT04360187). Patients who received crisaborole showed a greater reduction vs. those who received vehicle in change from baseline in PP-NRS score at Week 4 in the overall population, with a comparable reduction seen in patients aged ≥12 years (ClinicalTrials.gov, NCT04360187). Crisaborole-treated patients in the overall population and each age subgroup had consistent but comparable improvement in all primary and key secondary efficacy endpoints. In patients aged 2–6 years, 55.4% and 62.2% of those who received crisaborole and vehicle, respectively, experienced all-cause treatment-emergent adverse events (TEAEs). All-cause TEAEs occurred in 52.2% and 34.4% of patients aged 7–11 years who received crisaborole and vehicle, respectively; in the aged 12–17 years subgroup, 36% and 40% of patients who received crisaborole and vehicle experienced all-cause TEAEs, respectively. The TEAEs occurring in ≥1% of patients across all subgroups included atopic dermatitis and treatment-related application site pain. Application site pain was most frequently reported in the face and neck. Most TEAEs were mild. There were no new safety findings. Crisaborole was effective and well tolerated in Chinese and Japanese patients aged 2–17 years with mild-to-moderate AD.