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

Abstract

<h4>Background</h4>Prurigo 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.<h4>Objective</h4>To indirectly compare safety profiles of dupilumab and nemolizumab in PN, addressing trial design heterogeneity (efficacy endpoints, treatment durations, safety reporting).<h4>Method</h4>Following 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.<h4>Result</h4>In 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.