Dupilumab Demonstrates a Significantly Higher Likelihood of Achieving Improvements in Atopic Dermatitis Signs and Itch vs Nemolizumab at Week 16 in Combination With Topical Corticosteroids: Results From a Bucher Placebo-Adjusted Indirect Comparison

Introduction Atopic dermatitis (AD) is a chronic type 2 inflammatory disease, which often needs long-term treatment. The fully human monoclonal antibody dupilumab and the humanized monoclonal antibody nemolizumab have both demonstrated efficacy and safety in AD clinical trials. However, no head-to-head comparisons have been performed. In the absence of direct comparisons between medicinal products, Bucher indirect treatment comparisons (ITCs), in which treatment effects of the medicinal products are anchored to a common comparator (e.g. placebo), provide a robust and widely accepted method of evaluating relative efficacy. Objective To report the results of a placebo-anchored Bucher ITC comparing efficacy of dupilumab plus topical corticosteroids (TCS) every 2 weeks (q2w) versus nemolizumab plus TCS every 4 weeks (q4w) for moderate-to-severe AD over 16 weeks of therapy. Methods A placebo-anchored Bucher ITC was conducted using data from the published phase 3 clinical trial LIBERTY AD CHRONOS (NCT02260986) and the replicate phase 3 clinical trials ARCADIA 1 (NCT03985943) and ARCADIA 2 (NCT03989349). Data at Week 16 for the following doses were used: 300 mg dupilumab + TCS q2w, or placebo + TCS (LIBERTY AD CHRONOS), and 30 mg nemolizumab + TCS q4w, or placebo + TCS (ARCADIA 1 and 2). Non-responder imputation was used in all clinical trials for the binary outcomes, which were assessed in this ITC. Outcomes at Week 16 included proportion of patients achieving Investigator’s Global Assessment score 0/1 (IGA-0/1; clear/almost clear skin), ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75) and ≥4-point improvement from baseline in Peak Pruritus Numeric Rating Scale (PP-NRS ∆ ≥4). Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Meta-analysis ORs are provided for ARCADIA 1 and 2 combined. The number needed to treat (NNT) for achieving those outcomes were also computed to compare treatment benefits. Results Baseline disease characteristics were similar between LIBERTY AD CHRONOS and ARCADIA 1 and 2, supporting the use of Bucher ITC. Patients treated with dupilumab + TCS vs nemolizumab + TCS had a significantly higher likelihood of achieving IGA-0/1 (OR = 2.61; 95%CI 1.49, 4.57), EASI-75 (OR = 4.09, 95%CI 2.41, 6.96), and PP-NRS ∆ ≥4 (OR = 1.76, 95%CI 1.02, 3.02) at Week 16. When comparing these two treatments, dupilumab + TCS demonstrated greater treatment efficacy than nemolizumab + TCS across all 3 outcomes. The NNT to observe 1 patient achieving IGA 0/1, EASI-75, and PP-NRS ∆ ≥4 was 4, 3, and 3 respectively for dupilumab + TCS vs placebo + TCS, compared with 9, 8, and 5 respectively for nemolizumab + TCS vs placebo + TCS. Conclusions This placebo-anchored Bucher ITC analysis demonstrated that the likelihood of achieving improvements in AD signs and itch is significantly higher for patients treated with dupilumab + TCS q2w vs nemolizumab + TCS q4w at Week 16. Based on the NNT analysis, dupilumab + TCS demonstrated greater treatment efficacy across all assessed outcomes compared with nemolizumab + TCS, requiring substantially fewer patients to be treated to achieve the same clinical benefits.