Randomized evidence breadth and comparative maturity of systemic targeted therapies for prurigo nodularis: a time-aligned systematic review and network meta-analysis

OBJECTIVES: Randomized evidence for systemic targeted therapies in prurigo nodularis (PN) has expanded, but cross-trial differences limit valid comparison. We mapped randomized evidence and assessed comparative effects using exact Week-16 ≥ 4-point itch numerical rating scale response (NRS4). METHODS: MEDLINE, Embase, CENTRAL, and Web of Science were searched through 14 August 2026. Studies with extractable randomized arm-level Week-16 NRS4 data were synthesized using a fixed-effect contrast-based network meta-analysis. Risk of bias was assessed with RoB 2 and confidence with CINeMA. RESULTS: Twenty-four randomized studies were represented by 117 reports, but only seven cohorts (1,435 participants; 19 arms; 10 active nodes) contributed to the aligned network. Dupilumab (OR 4.04, 95% CI 2.42-6.75; low confidence) and global phase III nemolizumab (OR 5.81, 95% CI 3.81-8.86; low confidence) were effective versus placebo. The indirect nemolizumab-versus-dupilumab comparison was imprecise (OR 1.44, 95% CI 0.74-2.79; low confidence). CONCLUSIONS: Indirect evidence did not establish superiority of either biologic. The randomized evidence bases substantially exceeded the quantitatively comparable network, reflecting incomplete results availability and cross-trial differences. REGISTRATION: PROSPERO CRD420261401106.