Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Background Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. Methods In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. Findings Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. Interpretation Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis

15517 Eczema Area and Severity Index 90 (EASI-90) responder rates with abrocitinib and relationship with quality of life (QoL) and itch in patients with moderate to severe atopic dermatitis: Results from a randomized phase 3 clinical trial

Introduction: Abrocitinib is an oral Janus kinase 1 inhibitor under investigation for the treatment of moderate to severe AD. Design: Randomized, double-blind, placebo-controlled phase 3 trial (NCT03349060; JADE MONO-1). Methods: Patients ≥12 years old with clinical diagnosis of moderate to severe AD were randomly assigned (2:2:1) to once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. Eczema Area and Severity Index 90 (EASI-90), Dermatology Life Quality Index (DLQI), Children’s DLQI (CDLQI), and peak pruritus numeric rating scale (PP NRS; 0-10) were measured at baseline and weeks 2, 4, 8, and 12. Results: 154, 156, and 77 patients were treated with abrocitinib 200 mg, abrocitinib 100 mg, or placebo, respectively. Proportions of patients achieving ≥ 90% improvement in EASI-90 overall were 38.6% and 18.6% versus 5.3% at week 12 (difference from placebo [95% CI], 33.4% [24.3%-42.5%] and 13.3% [5.4%-21.2%]), with little difference between those with moderate baseline IGA (42.9% and 18.5% vs 6.7%; 36.2% [23.7%-48.7%] and 11.8% [1.0%-22.6%]) and severe baseline IGA (32.3% and 18.8% vs 3.2%; 29.0% [15.8%-42.2%] and 15.5% [4.1%-26.9%]). Greater proportions of week-12 EASI-90 responders versus nonresponders achieved no/mild alteration in QoL (89.0% vs 46.6%; per published [C]DLQI severity bands), ≥4-point improvement in PP-NRS (88.4% vs 25.1%; among those with baseline PP-NRS ≥4), and PP-NRS \u3c2 (70.0% vs 10.2%; among those with baseline PP-NRS ≥2). Conclusions: Abrocitinib therapy was associated with significantly greater EASI-90 responder rates versus placebo, regardless of baseline AD severity. EASI-90 response at week 12 corresponded with patients experiencing low impairment in QoL, clinically meaningful improvement in itch, and/or little-to-no itch

Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate