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

BACKGROUND

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.

OBJECTIVE

To indirectly compare safety profiles of dupilumab and nemolizumab in PN, addressing trial design heterogeneity (efficacy endpoints, treatment durations, safety reporting).

METHOD: 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.

RESULT: 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.