Comparative efficacy and safety of targeted systemic therapies for prurigo nodularis: a systematic review and network...

Prurigo nodularis (PN) is a chronic, intensely pruritic inflammatory skin disease. Multiple targeted biologic therapies have shown efficacy against placebo, but no randomized trial has directly compared these agents, leaving their relative efficacy and safety uncertain. To compare the efficacy and safety of dupilumab, nemolizumab, vixarelimab, and serlopitant for PN using network meta-analysis. PubMed, Embase, Cochrane and ClinicalTrials.gov were searched for randomized trials enrolling adults with PN that evaluated dupilumab, nemolizumab, vixarelimab, or serlopitant against placebo or one another. Risk of bias was assessed with RoB 2. A frequentist network meta-analysis was performed, with treatment effects expressed as risk ratios (RR) or standardized mean differences (SMD) with 95% CIs and surface under the cumulative ranking curve (SUCRA) values. Certainty of evidence was assessed using CINeMA. Eight randomized trials (1652 participants; mean age, 53.5 years) were included. At week 4, vixarelimab, 540 mg, produced the largest reduction in itch severity (SMD, - 2.36; 95% CI, - 3.28 to - 1.44), a finding sustained at week 16 (SMD, - 1.26; 95% CI, - 1.96 to - 0.55). Nemolizumab, 60 mg, produced the highest rate of clinically meaningful itch response (≥ 4-point PP-NRS improvement) at week 4 (RR, 6.77; 95% CI, 2.85-16.13) and was the only treatment with a sustained response advantage at weeks 12 to 16 (RR, 3.37; 95% CI, 1.45-7.84). For Investigator's Global Assessment success, nemolizumab, 30 mg, ranked highest (RR, 4.24; 95% CI, 2.46-7.29). No active treatment was associated with a significant increase in overall adverse events, serious adverse events, or infections; however, dupilumab was associated with more treatment discontinuations (RR, 13.01; 95% CI, 4.12-41.06) and serlopitant with more nasopharyngitis (RR, 5.41; 95% CI, 1.25-23.45). Certainty of evidence was low for most outcomes. Vixarelimab and nemolizumab ranked highest for itch severity and clinically meaningful itch response, respectively, while dupilumab demonstrated consistent efficacy across all outcomes, supporting the role of targeted biologic therapy in PN. Because comparative estimates are derived from indirect evidence, head-to-head trials are needed to confirm these findings.