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

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.