Peak Pruritus Numerical Rating Scale Research Articles

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2years with mild to moderate AD. We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2years with mild to moderate AD. ClinicalTrials.gov, NCT04360187.

Abrocitinib may improve itch and quality of life in patients with itch‐dominant atopic dermatitis

AbstractBackgroundPatients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear‐moderate lesions, also known as itch‐dominant AD, is a common clinical phenotype.ObjectivesTo evaluate abrocitinib efficacy in patients with moderate‐to‐severe AD who have itch‐dominant AD.MethodsThis post hoc analysis includes pooled data from clinical trials of patients with moderate‐to‐severe AD receiving abrocitinib (100 or 200 mg) as monotherapy (phase 2b; phase 3 JADE MONO‐1 and JADE MONO‐2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long‐term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch‐dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP‐NRS) score of 7−10 and Investigator's Global Assessment of 0−3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4‐point improvement in PP‐NRS (PP‐NRS4), PP‐NRS score of 0 (no itch) or 1 (little itch) in patients with PP‐NRS score ≥2 at baseline, ≥4‐point improvement from baseline in Patient‐Oriented Eczema Measure (POEM‐4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL]).ResultsIn the pooled monotherapy trials, 37% of patients had itch‐dominant AD at baseline. As early as Week 2, more patients with itch‐dominant AD achieved PP‐NRS4 with abrocitinib 100 mg (35%) and abrocitinib 200 mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP‐NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100 mg (28%) and abrocitinib 200 mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch‐dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%–87% and 62%–67% of patients had no itch‐moderate itch and clear‐moderate lesions by weeks 24 and 48, respectively.ConclusionsAbrocitinib is highly efficacious in patients with itch‐dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL.Trial Registration NumbersNCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822.

Total eosinophil count as a biomarker for therapeutic effects of upadacitinib in atopic dermatitis over 48 weeks.

Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg. A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.

Long-term effectiveness and safety of upadacitinib for Japanese patients with moderate-to-severe atopic dermatitis: a real-world clinical study

Background Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). Objectives To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). Methods This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator’s global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. Results From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. Conclusions Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.

Sustained Effectiveness of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A 48-Week Real-World Study.

Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator's global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12.

Efficacy and safety of nemolizumab and topical corticosteroids for prurigo nodularis: Results from a randomised, double-blind, placebo-controlled, phase II/III clinical study in patients aged ≥13 years.

Prurigo nodularis, a chronic inflammatory skin condition, adversely affects the quality of life of affected individuals. Current treatment options for prurigo nodularis in Japan are limited. To evaluate the optimal dose, efficacy, and safety of long-term treatment with nemolizumab in patients with prurigo nodularis in Japan. In a 16-week, double-blind, phase II/III study, patients aged ≥13 years with prurigo nodularis were randomly assigned (1:1:1) to nemolizumab 30 mg, 60 mg, or placebo groups, with concomitant topical corticosteroids, every 4 weeks. The primary efficacy end point was the percentage change in the weekly mean Peak Pruritus Numerical Rating Scale (PP-NRS) score (range, 0 to 10, with higher scores indicating worse itching) from baseline to week 16. Secondary efficacy end points assessed the impact of treatment on pruritus, prurigo nodularis severity, sleep, and quality of life. At week 16, the least-squares mean percentage change from baseline in the PP-NRS score was -61·1% in the nemolizumab 30 mg group (n = 77), -56·0% in the 60 mg group (n = 76), and -18·6% in the placebo group (n = 76). Differences between both nemolizumab groups and placebo were significant; the difference between the 30 mg and placebo groups was -42·5% (95% confidence interval [CI], -51·9 to -33·1; P<0·0001), and between the 60 mg and placebo groups was -37·4% (95% CI, -46·7 to -28·1; P<0·0001). Nemolizumab-treated patients also had greater improvements in the number and severity of prurigo nodules, and in sleep and quality of life compared with the placebo group. Both nemolizumab doses were well tolerated. Improvements in prurigo nodularis were greater following nemolizumab treatment, despite continuation of topical corticosteroids in both groups. (Funded by Maruho; jRCT number, 2011200017.).

Tapinarof Cream 1% Once Daily Improves Patient-Reported Outcomes 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) for the treatment of plaque psoriasis was efficacious and well tolerated. Plaque psoriasis affecting the head and neck region occurs commonly, with a high impact on patients’ health-related quality of life, through pruritus and psychological distress. Patients may consider topicals unacceptable for scalp/facial use due to poor cosmetic properties (e.g., greasiness), leading to low medication adherence. There is a need for efficacious, cosmetically elegant, non-steroidal topicals that can be used without restrictions.Objective: To assess patient-reported outcomes (PROs) with tapinarof cream for adults with mild to severe plaque psoriasis in the head and neck region, including the scalp, in a phase 4, open-label trial.Methods: Adults with head and neck region target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe) received tapinarof for 12 weeks. PROs included Peak Pruritus Numerical Rating Scale (PP-NRS) score for the head and neck region; achievement of ≥4-point reduction in PP-NRS score; Dermatology Life Quality Index (DLQI) score by visit; and responses to a Patient Satisfaction Questionnaire© (PSQ) at Week 12.Results: 31 patients received tapinarof; 58.1% (18/31) had the target lesion on the scalp. Baseline mean PP-NRS (head and neck region) and total DLQI scores were 5.8 and 9.7, respectively, demonstrating significant pruritus and disease impact. Improvement in mean PP-NRS score was demonstrated at Week 1 (–1.6), the earliest assessment, surpassing the minimal clinically important ≥4-point improvement by Week 12 (−4.2). At Week 12, 70.0% (n=14/20) achieved ≥4-point reduction in PP-NRS score. Mean DLQI minimal clinically important difference of −4.0 was demonstrated as early as Week 1 (−4.0), improving to −7.2 at Week 12. Most patients strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (93.3%), quick absorption (96.7%), application ease (86.7%), efficacy (83.3%), and confidence in tapinarof (83.3%). Compared with topicals used previously for plaque psoriasis, most strongly agreed or agreed that tapinarof was more effective (76.9%) and easier to use (76.9%).Conclusions: In patients with plaque psoriasis affecting the head and neck region, tapinarof cream 1% QD demonstrated rapid and clinically meaningful improvements in patient-reported pruritus and disease impact as early as Week 1, the first assessment, with continued improvement through Week 12. Patients reported high rates of satisfaction and positive perceptions of tapinarof.Funding Support: Dermavant Sciences, Inc.

Efficacy of Abrocitinib and Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis With Severe Itch at Baseline and in Subgroups by Baseline Thresholds of Severe Itch: A Post Hoc Analysis of the JADE COMPARE and JADE DARE Clinical Trials

Introduction: In phase 3 trials, abrocitinib provided more rapid and greater itch relief than dupilumab in patients with moderate-to-severe atopic dermatitis (AD). We examined the efficacy of abrocitinib versus dupilumab in patients with severe itch at baseline (BL) and in subgroups by BL thresholds of severe itch.Methods: Data were pooled from patients treated with abrocitinib 200 mg or dupilumab 300 mg in JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367). Patients with severe itch at BL (Peak Pruritus Numerical Rating Scale [PP-NRS] ≥7), and subgroups by BL PP-NRS 7-10 were assessed for achievement of ≥4-point improvement in PP-NRS (PP-NRS4) and PP-NRS 0/1 (itch free state). Subgroups were also assessed for achievement of Patient Oriented Eczema Measure (POEM) score ≤2 (clear/almost clear AD), and Dermatology Life Quality Index (DLQI) score of 0/1 (no impact on quality of life [QoL]).Results: This analysis comprised 875 patients (abrocitinib, 453; dupilumab, 422) with severe itch at BL. Median (Q1, Q3) BL score for PP-NRS was 8.0 (7.0, 9.0) in the abrocitinib arm and 8.0 (7.0, 9.0) in the dupilumab arm; 22.0 (19.0, 26.0) and 22.0 (19.0, 27.0) for POEM; 16.0 (11.0, 20.5) and 16.0 (11.0, 20.0) for DLQI. In the overall group, PP-NRS4 responses were greater with abrocitinib versus dupilumab as early as week 2 (56% vs 32%) and sustained through week 16 (73% vs 69%). Stringent PP-NRS 0/1 responses were greater with abrocitinib versus dupilumab at weeks 2 (15% vs 3%) and 16 (35% vs 21%). Across patient subgroups by BL PP-NRS 7-10, greater proportions achieved PP-NRS4 and PP-NRS 0/1 with abrocitinib versus dupilumab at weeks 2 and 16. Greater proportions across subgroups achieved POEM ≤2 with abrocitinib compared with dupilumab at week 16 (BL PP-NRS7, 33% vs 10%; BL PP-NRS8, 29% vs 20%; BL PP-NRS9, 39% vs 16%; BL PP-NRS10, 31% vs 23%). In the overall group, greater proportions achieved DLQI 0/1 with abrocitinib versus dupilumab at weeks 2 (19% vs 6%) and 16 (38% vs 27%). Across subgroups, DLQI 0/1 responses with abrocitinib were generally greater than dupilumab at weeks 2 and 16.Conclusions: In patients with moderate-to-severe AD who had severe itch at BL, abrocitinib provided more rapid and complete/near complete itch relief and improved QoL than dupilumab as early as 2 weeks of treatment. These results were consistent across subgroups by various BL thresholds of severe itch.

Effectiveness of Dose Increase in Upadacitinib from 15 mg to 30 mg for Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Clinical Practice in Japan.

Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as atreatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.

Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT.

Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial. We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP. LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS). The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36. The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis. ClinicalTrials.gov identifier NCT04206553.

Real-world effectiveness and safety of abrocitinib in 12 Japanese patients with atopic dermatitis and transcriptome analysis with peripheral blood.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by recurrent, pruritic, and localized eczema. Various types of new drugs have been recently investigated for treating AD. The efficacy and safety of abrocitinib in treating AD has been reported in clinical trials, but the real-world data from Japan has not been reported. Herein, we analyzed 12 Japanese patients with AD treated with 100 mg of abrocitinib using our real-world data. We also performed transcriptome analysis with peripheral blood to investigate the effects of abrocitinib on cytokine expressions and inflammatory pathways in AD from three patients. This study included patients with moderate to severe AD treated with abrocitinib at Gunma University Hospital, Japan. All patients were systemic treatment-naïve. All patients received a 100-mg dose of abrocitinib daily, and used strong or very strong topical steroids and moisturizers. The Eczema Area and Severity Index (EASI) response analysis revealed that after 4 weeks, 25% (three of 12) of the cases reached a 75% reduction in the EASI score (EASI-75) and a 90% reduction in the EASI score (EASI-90). After 12 weeks, 83.3.% (10 of 12), 41.6% (five of 12), and 16.7% (two of 12) of the patients reached EASI-50, a 75% reduction in the EASI score (EASI-75), and EASI-90. Peak Pruritus Numerical Rating Scale was achieved in nine patients (75%) at week 12. The most frequent adverse reaction was acne (six cases [50%]). Gene Ontology pathway analysis using Differentially expressed genes from RNA sequencing analysis revealed attenuation of defense responses to biotic stimulus, virus, and cytokines. Th2 cytokine expression was not suppressed, but several chemokines, especially CXCL1, were suppressed by abrocitinib treatment. Our results indicate abrocitinib as a fast-acting and highly antipruritic agent that is effective for moderate skin eruptions.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

515 - Rapid and early onset of itch relief with tapinarof cream 1% once daily in two pivotal phase 3 trials in adults and children down to two years of age with atopic dermatitis

Abstract Introduction Itch is the most bothersome symptom for patients with atopic dermatitis (AD), with a significant negative impact on health-related quality of life. Rapid onset of pruritus relief with sustained efficacy is a key outcome for AD therapies. In a phase 2 trial in adults and adolescents with moderate to severe AD, tapinarof cream 1% once daily (QD) demonstrated efficacy versus vehicle and was well tolerated. Objective Here, we evaluate time to onset of itch relief in the pivotal phase 3 trials with tapinarof cream 1% QD in the treatment of adults and children down to 2 years of age with AD. Materials and Methods In ADORING 1 and 2, two identical, double-blind, vehicle-controlled trials, patients were randomized 2:1 to tapinarof cream 1% or vehicle QD for 8 weeks. Patients with a Validated Investigator Global Assessment for Atopic DermatitisTM score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were included. Efficacy endpoints that evaluated itch relief were mean changes in Peak Pruritus-Numerical Rating Scale (PP-NRS) score (daily and by visit [Weeks 1, 2, 4, and 8]) from baseline through Week 8. The PP-NRS considers a person’s worst itch over the past 24 hours, assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). Daily PP-NRS scores were recorded in diaries. Patients aged ≥12 years self-completed the PP-NRS, while caregivers completed it for children aged &amp;lt;12 years. Results 407 and 406 patients were randomized in ADORING 1 and 2. At baseline, mean (standard deviation [SD]) PP-NRS scores were 6.7 (2.4) and 6.8 (2.3) in both trials, respectively. For daily evaluations of itch from baseline, greater reductions in PP-NRS scores (mean [SD]) for tapinarof versus vehicle were observed as early as Day 1, 24 hours after initial application, in ADORING 1 (–1.2 [2.2] vs –0.9 [2.0]) and Day 2 in ADORING 2 (–1.6 [2.4] vs –1.4 [2.1]). Improvements in daily PP-NRS scores (mean [SD]) with tapinarof versus vehicle continued through the first 2 weeks (Day 14; –3.0 [2.8] vs –2.0 [2.4] and –2.9 [2.7] vs –1.8 [2.6]), and through Week 8 of both trials. There were statistically significant and clinically meaningful reductions in mean weekly PP-NRS scores as early as Week 1, the first assessment, for patients treated with tapinarof compared with vehicle (–2.0 vs –1.2 [P&amp;lt;0.0001]) and (–2.0 vs –1.3 [P=0.0010]), in ADORING 1 and 2, respectively. Significantly greater reductions in mean PP-NRS scores with tapinarof versus vehicle were seen for all visits through Week 8 (–4.1 vs –2.6 and –4.1 vs –2.4 [both P&amp;lt;0.0001]), for both trials. Conclusions Tapinarof cream 1% QD demonstrated rapid, clinically meaningful, and significant onset of pruritus relief as early as 24 hours after initial application compared with vehicle. Improvements in itch with tapinarof cream increased through Week 8 in both trials in adults and children down to 2 years with AD.

523 - Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a phase 2b trial (STREAM-AD)

Abstract Introduction/Background Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing). Objectives To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD. Methods STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to &amp;lt;75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD], n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388). Results Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of –32.1% (95% CI: –43.9, –20.3; P&amp;lt;0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, –27.3 (95% CI: –39.1, –15.6; P&amp;lt;0.0001); 125 mg, –22.2 (95% CI: –34.0, –10.4; P=0.0002); and 62.5 mg, –30.2 (95% CI: –41.9, –18.5; P&amp;lt;0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P&amp;lt;0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS ≥4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified. Conclusions In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups.

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.

530 - Treatment efficacy in patients with moderate-to-severe atopic dermatitis who switched from dupilumab to abrocitinib in JADE EXTEND, a phase 3 long-term extension study

Abstract Background Abrocitinib, an oral, once-daily, Janus kinase 1–selective inhibitor, and dupilumab, an anti–interleukin 4 receptor α monoclonal antibody, have been approved for the treatment of patients with moderate-to-severe atopic dermatitis (AD). The efficacy of abrocitinib and dupilumab as monotherapy or in combination with medicated topical therapy has been demonstrated in multiple phase 3 clinical trials. As is the case with many therapies, some patients with AD may need to discontinue treatment with dupilumab (due to inadequate efficacy, intolerable side-effects, patient choice, or other reasons) and switch to other systemic therapies. Objective To evaluate the long-term treatment response in patients with moderate-to-severe AD who switched from dupilumab to abrocitinib, as it is valuable information for prescribers and patients to consider when making treatment decisions. Methods The phase 3 JADE COMPARE trial (NCT03720470) evaluated the efficacy of abrocitinib (100 mg or 200 mg once daily) and dupilumab (300 mg every 2 weeks) versus placebo in combination with topical medicated therapy in patients with moderate-to-severe AD through week 16. After a wash-out period, dupilumab-treated patients from JADE COMPARE who enrolled in the ongoing long-term extension trial JADE EXTEND (NCT03422822; clinical data cutoff: Sept 25, 2021) were randomised to receive double-blinded treatment with abrocitinib 100 mg or 200 mg. This post hoc analysis evaluated the response to dupilumab through week 16 in JADE COMPARE and thereafter in JADE EXTEND following a switch to abrocitinib through week 104 of total treatment duration/week 84 of abrocitinib treatment. Assessments included Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (IGA 0/1), ≥75% or ≥90% improvement from baseline in Eczema Area and Severity Index (EASI-75 or EASI-90), ≥4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS4; PP-NRS used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi), and a PP-NRS score of 0 or 1 (PP-NRS 0/1). JADE EXTEND data are presented as observed; patients with missing data at a visit were excluded. Analyses included both dupilumab responders and non-responders. Results Overall, 242 patients were treated with dupilumab in JADE COMPARE (mean age: 37 years; IGA score 4: 33%). Of those, 203 enrolled in JADE EXTEND and received abrocitinib 200 mg (n=73) or abrocitinib 100 mg (n=130). After 16 weeks of treatment with dupilumab in JADE COMPARE, the proportion of responders was 39% for IGA 0/1, 66% for EASI-75, 39% for EASI-90, 57% for PP-NRS4, and 24% for PP-NRS 0/1. As early as 2 weeks after switching to abrocitinib (200 mg/100 mg) in JADE EXTEND, the proportion of responders was observed to increase in a dose-dependent manner, respectively, for IGA 0/1 (61%; 51%), EASI-75 (90%; 85%), EASI-90 (60%; 54%), PP-NRS4 (81%; 72%), and PP-NRS 0/1 (47%; 37%). Long-term efficacy was observed out to week 84 (Figure). Conclusions In patients with moderate-to-severe AD who received prior treatment with dupilumab, switching to abrocitinib resulted in dose-dependent increases in the proportion of responders as early as week 2 after treatment with abrocitinib. This efficacy continued to be observed long-term through week 84 of abrocitinib treatment.

538 - Physician-assessed effectiveness and patient-reported outcomes in adult and adolescent patients with atopic dermatitis in the Asian subpopulation treated with dupilumab: real-world insights 1 year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction In multiple randomized controlled clinical trials, dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD). Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Comprehensive data on Asian patients with moderate-to-severe AD treated with dupilumab are limited. Objectives To report patient-reported outcomes and physician-assessed AD clinical measures to evaluate disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment in Asian patients. The baseline disease severity and patient demographics have been reported previously1. Methods This 5-year, multinational, multicentre, prospective, observational study (GLOBOSTAD; NCT03992417) included Asian patients ≥12 years-old with moderate-to-severe AD who initiated dupilumab treatment based on country-specific prescribing criteria. Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed in patients self-reported as Asian for enrolment/safety (N = 204; data cutoff: March 2023) and follow-up (N = 194) populations. Results During the study, EASI (&amp;gt;21 = severe; ≤7 = mild/no disease) score improved from 28.0 (12.1), mean (SD) at baseline to 7.4 (8.5) at 3 months, 5.7 (6.9) at 6 months, and was sustained until the end of observation period, 12 months, at 4.7 (7.1). Similarly, SCORAD (&amp;gt;50 = severe; &amp;lt;25 = mild/no disease) score improved from 61.5 (16.9) at baseline to 25.4 (16.6) at 3 months, 22.5(14.8) at 6 months, and further improved to 18.6 (13.3) at 12 months. During the study, patients also reported early improvements in POEM, mean (SD) from 19.1 (7.3) at baseline to 8.0 (5.8) at 3 months, 7.6 (5.5) at 6 months, and to 7.2 (5.0) at end of observation period (12 months); PP-NRS decreased from 5.7 (2.3) to 2.1 (2.2) to 1.7 (1.8), and to 1.4 (1.7) at 3 months, 6 months, and 12 months respectively; and DLQI improved from 13.2 (7.4) to 4.9 (4.6) to 4.0 (3.8), and to 4.1 (4.0) at 3 months, 6 months and 12 months respectively. Dupilumab-related adverse events were reported in 44 (21.5%) patients while 4 (2.0%) reported dupilumab-related severe adverse events. Conclusion In Asian patients, the initiation of dupilumab treatment led to early improvements in all AD outcome measures, sustained throughout the 1-year observational period. Safety and treatment effectiveness were consistent with overall population.

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.

541 - Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 3-year data from the PROSE registry

Abstract Background Dupilumab has shown efficacy in the treatment of atopic dermatitis (AD) in clinical trials, but there is a need for long-term data on patients starting dupilumab treatment for atopic dermatitis in a real-world setting. Methods PROSE (NCT03428646) is an ongoing 5-year, prospective, observational study of patients aged ≥12 years who initiated commercially available dupilumab treatment for AD per country-specific prescribing information. Patients received a loading dose of dupilumab at baseline, without restrictions on post-baseline dosing changes or concomitant medication and were encouraged to stay in the study if they discontinued dupilumab. Data presented are descriptive, from a 3-year interim analysis. Results 857 patients were enrolled. In these patients, mean (SD) age was 40.1 (17.9) years, AD duration 17.4 (16.2) years, and dupilumab treatment duration 23.1 (13.7) months (M). Mean (SE) baseline EASI total score was 16.2 (0.4), Pruritus Numerical Rating Scale (NRS) 7.1(0.1), Dermatology Life Quality Index (DLQI) 13.3 (0.3), and skin pain NRS 5.4 (0.1). 189 (22.1%) patients had withdrawn by data cut-off; the most common reasons for discontinuation were withdrawal of consent in 76 patients and loss to follow-up in 30. Mean (SE) EASI total score was 5.6 (0.4) at 3M, 2.9 (0.2) at 12M, 2.7 (0.4) at 24M, and 1.7 (0.3) at 36M. Mean (SE) change from baseline in Peak Pruritus NRS was −3.5 (0.2) at 3M, −4.2 (0.2) at 12M, −4.7 (0.2) at 24M, and −5.1 (0.3) at 36M. Mean (SE) change from baseline in DLQI was −7.4 (0.3) at 3M, −8.3 (0.7) at 12M, −9.2 (0.9) at 24M, and −8.8 (1.5) at 36M. Mean (SE) change from baseline in skin pain NRS was −3.3 (0.3) at 3M, −3.8 (0.2) at 12M, −4.0 (0.3) at 24M, and −4.6 (0.3) at 36M. Safety findings were consistent with the previously described safety profile of dupilumab. Conclusion In this interim analysis of the PROSE registry, sustained disease control was observed in patients with moderate-to-­severe AD for up to 3 years after initiating dupilumab treatment.

Effectiveness and safety of deucravacitinib treatment for moderate-to-severe psoriasis in real-world clinical practice in Japan

Background Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. Objectives We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. Methods We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. Results At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50–80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. Conclusions Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.