AUTHOR=Feng Wenzhe , Wang Dongyang , Tan Kaiyue , Zhang Xiaojie 

TITLE=Comparative safety profiles of dupilumab and nemolizumab in prurigo nodularis: an indirect META-analysis to inform clinical decision-making

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1626395

DOI=10.3389/fmed.2025.1626395

ISSN=2296-858X

ABSTRACT=BackgroundPrurigo nodularis (PN), a chronic inflammatory skin disease with significant disease burden, lacks effective therapies. Dupilumab (IL-4Rα inhibitor) and nemolizumab (IL-31 receptor antagonist) show efficacy in trials but have heterogeneous safety data without direct comparisons.ObjectiveTo indirectly compare safety profiles of dupilumab and nemolizumab in PN, addressing trial design heterogeneity (efficacy endpoints, treatment durations, safety reporting).MethodFollowing PRISMA guidelines, five RCTs (dupilumab: 2 trials; nemolizumab: 3 trials) were analyzed. Safety outcomes [adverse events (AEs), serious AEs (SAEs), treatment discontinuation, mechanism-specific events] were standardized via time-proportional hazard models. Risk ratios (RR) and absolute risk differences (ARD) were calculated using Cochrane tools and indirect comparison frameworks.ResultIn standardized indirect comparisons, dupilumab and nemolizumab showed broadly similar safety profiles for overall adverse events (indirect RR = 1.11, 95% CI:0.85–1.47; moderate certainty), serious adverse events and treatment discontinuation. Exploratory analyses of mechanism-specific events revealed non-significant directional differences requiring cautious interpretation: dupilumab showed a numerically higher incidence of conjunctivitis (RR = 2.01, 95% CI:0.29–13.77) with confidence intervals spanning two orders of magnitude, while nemolizumab showed a similar pattern for edema (RR = 1.64, 95% CI:0.52–5.18). These signals, derived from sparse event data (n ≤ 15 cases) and overlapping confidence intervals across all comparisons, should be regarded as hypothesis-generating rather than confirmatory evidence. Limitations inherent to indirect methodology – including trial design heterogeneity (endpoint definitions: IGA PN-S vs. PP-NRS; duration:12–24 weeks) and absence of severity-stratified reporting – preclude definitive safety conclusions. All comparisons must be interpreted within the constraint of unmeasured confounding factors potentially influencing indirect estimates.