Clinically Meaningful Improvements in Quality of Life, Including Sleep, With Two-Week and Monthly Dosed Rademikibart: A Phase 2 Randomized Trial in Adults With Moderate-to-Severe Atopic Dermatitis

Background: Rademikibart, a potent, next-generation, optimized IL-4Rα-targeting antibody, achieved its primary and secondary endpoints as a treatment for adults with moderate-to-severe atopic dermatitis (AD) in the CBP-201-WW001 Phase 2, randomized, double-blind, placebo-controlled trial (NCT04444752). Objectives: To investigate meaningful improvements in both health-related quality of life (HRQoL) and AD, including the first assessments of sleep, across 16 weeks of rademikibart therapy, dosed 300 mg every other week (Q2W) or 300 mg every fourth week (Q4W). Methods: Exploratory and post hoc analyses of Dermatology Life Quality Index (DLQI) and Severity Scoring of AD (SCORAD) were conducted with analysis of covariance (ANCOVA) and last observation carried forward (LOCF) or Fisher's Exact Test and nonresponder imputation. Results: Least squares mean DLQI and SCORAD scores decreased statistically significantly, without evidence of plateauing across 16 weeks of treatment, by approximately 50% with both Q2W (N = 57) and Q4W (N = 56), versus approximately 28% with placebo (N = 56), for both measures. At Week 16, greater proportions of patients in the Q2W and Q4W arms versus placebo achieved clinically important difference criteria of ≥ 4-point DLQI improvement among patients with ≥ 4 points at baseline (66.6% and 70.0% vs. 38.2%; p < 0.01) and ≥ 35% SCORAD improvement (63.2% and 67.9% vs. 37.5%; p < 0.01). Greater proportions of patients achieved a DLQI score of ≤ 5, indicating no/little impact of AD on their HRQoL, with Q2W (54.4%, p < 0.01) and Q4W (48.2%, p < 0.05) versus placebo (28.6%). Least squares mean SCORAD subscores (0–10 visual analogue scale) improved for insomnia (−4.7 and −4.1 vs. −2.7; p ≤ 0.01) and pruritus (−4.3 and −3.9 vs. −2.4; p ≤ 0.02), with 50.0%–72.7% of rademikibart-treated patients reporting ≥ 3-point or ≥ 4-point sleep and pruritus SCORAD improvement. Conclusions: Patients experienced meaningful AD and HRQoL improvements by first or second assessment (Weeks 2 or 4). Notably, sleep improved substantially. Responses were comparable with rademikibart Q2W and Q4W.