34587 Efficacy of ruxolitinib cream for the treatment of atopic dermatitis by anatomic region: Pooled analysis from two randomized phase 3 studies

Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease. Two phase 3 studies (TRuE-AD1/TRuE-AD2) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks of double-blind treatment, and thereafter continued in a long-term, 44-week period of the studies. In this pooled analysis, mean percentage change from baseline in Eczema Area and Severity Index (EASI) anatomic region subscores is reported up to Week 8 (n = 1208). For the head and neck region, patients applying 0.75%/1.5% ruxolitinib cream (vs vehicle) achieved mean improvements of 59.3%/55.8% (vs 13.4%), 70.4%/71.3% (vs 22.4%), and 70.0%/78.7% (vs 45.0%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Results were similar for the upper limbs region (48.5%/54.7% [vs 13.3%], 66.6%/70.3% [vs 25.0%], and 73.5%/74.9% [vs 35.1%] all P \u3c.0001). For the trunk region, patients achieved mean improvements of 49.8%/60.0% (vs 12.1%), 67.3%/73.8% (vs 15.0%), and 72.7%/81.0% (vs 15.6%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Similar results were observed for the lower limbs region (46.0%/48.2% [vs 16.3%], 65.9%/66.2% [vs 13.9%], and 76.3%/74.9% [vs 39.8%]; all P \u3c.0001). Ruxolitinib cream was well tolerated, with an adverse event profile similar to vehicle. In summary, ruxolitinib cream demonstrated significant improvements vs vehicle in patients with AD across anatomic regions as early as Week 2

Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA)

Tapinarof, a novel, first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) modulating agent (TAMA), is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of pro-inflammatory cytokines, including interleukin-17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells, and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early phase clinical trials of tapinarof cream in the treatment of psoriasis

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Durability of Response to Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis After Treatment Discontinuation in a Phase 2b Trial

ntroduction: Multiple clinical trials showed that 12 weeks of abrocitinib monotherapy was safe and effective for the treatment of moderateto-severe atopic dermatitis (AD). The reversibility of pharmacologic activity after abrocitinib discontinuation was not described. Methods: This post hoc analysis used data from a phase 2b study to evaluate maintenance of disease control during a 4-week drug-free follow-up period in patients with moderate-tosevere AD treated with once-daily abrocitinib (200 mg/100 mg) or placebo for 12 weeks. Proportions of patients who achieved and maintained 50% or 75% improvement in Eczema Area and Severity Index (EASI-50/EASI75), an Investigator’s Global Assessment (IGA) score of 0/1, or at least a 4-point improvement in the pruritus numeric rating scale (pruritus NRS4) were determined. Biomarkers of Janus kinase inhibition and AD disease were measured in blood samples. Results: Among week 12 responders to abrocitinib 200 mg, 77.4%, 42.3%, 21.1%, and 42.9% maintained their EASI-50, EASI-75, IGA, and pruritus NRS4 response at week 16; corresponding proportions of week 12 responders maintaining response to abrocitinib 100 mg were 51.9%, 35.0%, 33.3%, and 43.5%, respectively. Four weeks after abrocitinib discontinuation, all AD biomarkers reverted towar

Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR])

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International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale

INTRODUCTION: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings. METHODS AND ANALYSIS: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events. ETHICS AND DISSEMINATION: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03661866, pre-results

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

The Treat-to-Target Project in Atopic Dermatitis: One Year On

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been deve loped previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development

Spesolimab efficacy and safety in patients with moderate-to-severe palmoplantar pustulosis: a multicentre, double-blind, randomised, placebo-controlled, phase IIb, dose-finding study

Introduction: We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP). Methods: This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician’s Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed. Results: 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from − 14.6% (95% confidence interval [CI]: − 31.5%, 2.2%) to − 5.3% (95% CI: − 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference − 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo. Conclusion: The primary objective to demonstrate a non-flat dose–response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518)