Efficacy and Safety of IL ‐ 4Rα Inhibitors for Atopic Dermatitis: A Systematic Review and Meta Analysis of Randomised Controlled Trials

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting over 200 million people globally. Emerging IL‐4Rα–targeted monoclonal antibodies have demonstrated strong efficacy and safety in clinical trials, warranting comparison with dupilumab, the current systemic standard. This meta‐analysis synthesises available evidence on their efficacy and safety. PubMed, Embase and Cochrane Library were systematically searched in April 2025 for randomised controlled trials (RCTs) comparing IL‐4Rα–targeting monoclonal antibodies versus placebo in moderate‐to‐severe AD, with EASI‐75 as the primary outcome. Non‐RCTs and trials using concomitant corticosteroids were excluded. Risk of bias was assessed using the Cochrane RoB‐2 tool. Analyses were performed in R (v4.5.0), with heterogeneity evaluated by Cochran Q and I 2 statistics. Nineteen RCTs comprising 4465 patients met inclusion criteria. At week 16, IL‐4Rα inhibitors showed sustained efficacy across EASI‐50/75/90, IGA 0/1 and pruritus reduction. Dupilumab remained the most validated agent, with durable effects, low heterogeneity and favourable safety. Among novel biologics, stapokibart and rademikibart demonstrated the most promising results, achieving superior EASI‐90 and ≥ 4‐point PP‐NRS responses: stapokibart (OR 4.94; 95% CI 3.20–7.61) and rademikibart (OR 4.61; 95% CI 1.68–12.65), though the latter showed higher odds of adverse events. Other agents (MG‐K10, GR1802, 611, AK120) provided encouraging but limited data. IL‐4Rα inhibitors represent effective and safe therapies for moderate‐to‐severe AD. Dupilumab remains the reference standard, while stapokibart and rademikibart emerge as promising next‐generation options. Further large, long‐term, head‐to‐head RCTs are warranted to confirm their comparative performance. PROSPERO Registration: CRD420251129343.