Comparing the Efficacy and Safety of Nemolizumab Versus Anti-interleukin Monoclonal Antibody Therapies in Combination with Topical Treatments for Moderate-to-Severe Atopic Dermatitis Using Network Meta-analysis

INTRODUCTION: Atopic dermatitis (AD) is a complex disease with clinical heterogeneity. Nemolizumab is a novel interleukin (IL)-31 receptor alpha inhibitor that has demonstrated efficacy in managing moderate-to-severe AD. However, there are no head-to-head trials that compare nemolizumab with other anti-IL-4/13 monoclonal antibodies (mAbs). To support clinical decision-making, the comparative efficacy and safety of nemolizumab versus other advanced systemic therapies, in combination with topical treatments, were estimated using network meta-analyses (NMAs). METHODS: Randomized controlled trials (RCTs) investigating advanced systemic therapies for moderate-to-severe AD in adolescents (12-17 years) and adults (≥ 18 years) were identified through a systematic literature review (searches conducted 31 March 2025, CRD42023492392). The trial results were analyzed in fixed- and random-effects Bayesian NMA models. Outcomes included ≥ 75% improvement in the Eczema Area Severity Index (EASI-75), an Investigator's Global Assessment (IGA) score of 0 or 1 (IGA success), treatment-emergent adverse events, and discontinuations due to adverse events. Analyses for all endpoints were conducted at week 16. This publication presents a targeted comparison of licensed anti-IL mAbs. RESULTS: Twenty-two RCTs were included in the NMA. When measuring response through EASI-75 and IGA success, no statistically significant differences were observed between nemolizumab and all other anti-IL mAbs in CsA-experienced adults or CsA-naïve adolescents. In CsA-naïve adults, only lebrikizumab demonstrated statistically superior efficacy against nemolizumab. Nemolizumab demonstrated a comparable safety profile with other available treatments. CONCLUSIONS: The results of this study suggest that compared with other anti-IL mAb therapies for the treatment of moderate-to-severe AD, nemolizumab has similar efficacy in achieving EASI-75 and IGA success, and a comparable safety profile. This is in addition to nemolizumab's well-demonstrated efficacy in improving itch. Nemolizumab may be particularly beneficial in clinical settings where patients and physicians are seeking to manage AD with a well-tolerated therapeutic.