Nemolizumab Versus Dupilumab in the Treatment of Prurigo Nodularis: Systematic Literature Review and Network Meta-analysis

Prurigo nodularis (PN) is a chronic skin condition characterized by severe, persistent pruritus and impairment in health-related quality of life. Dupilumab and nemolizumab are the only treatments approved by the US Food and Drug Administration and the European Medicines Agency for PN. In the absence of head-to-head comparisons, this study evaluated the comparative clinical efficacy and safety of nemolizumab versus dupilumab in an indirect treatment comparison. A systematic literature review (SLR) identified clinical trials reporting efficacy and/or safety outcomes in PN. Searches were conducted on 1 December 2025 in Embase, MEDLINE and MEDLINE In-Process, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and PsycInfo. Evidence from the SLR was synthesized using a Bayesian network meta-analysis (NMA) to generate comparative estimates. Sensitivity analyses assessed robustness to assumptions regarding missing data and differences in concomitant topical corticosteroid or calcineurin inhibitor use. Five trials were included. In base-case analyses, nemolizumab generally demonstrated greater estimated efficacy than dupilumab across pruritus-related outcomes, with statistically significant differences for selected endpoints and time points. Estimated treatment differences significantly favored nemolizumab for change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) at 24 weeks (mean difference - 1.30; 95% credible interval [CrI] - 2.49 to - 0.18), PP-NRS response (≥ 4-point improvement) at 12 weeks (odds ratio [OR] 3.27; 95% CrI 1.41 to 7.27), and the composite endpoint of Investigator Global Assessment success and PP-NRS response at 12/16 weeks (OR 3.35; 95% CrI 1.19 to 10.09). At earlier time points (4-6 weeks), change from baseline in PP-NRS also significantly favored nemolizumab. Sensitivity analyses were consistent with base-case findings. Treatment-emergent adverse events were similar between treatments. These findings suggest that nemolizumab may provide greater improvement in key pruritus and disease severity outcomes compared with dupilumab in patients with PN, although uncertainty remains for several endpoints.