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

## TL;DR

This study compares the safety of two drugs, dupilumab and nemolizumab, for treating prurigo nodularis, finding similar overall safety profiles but noting some potential differences in specific side effects.

## Contribution

The study provides an indirect meta-analysis comparing the safety profiles of dupilumab and nemolizumab in prurigo nodularis, addressing trial heterogeneity.

## Key findings

- Dupilumab and nemolizumab showed similar overall adverse event rates with moderate certainty.
- Exploratory analyses suggested possible higher risks of conjunctivitis with dupilumab and edema with nemolizumab, though not statistically significant.
- Limitations include trial design differences and sparse event data, making conclusions hypothesis-generating rather than confirmatory.

## Abstract

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.

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

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.

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.