Direct randomized evidence for systemic targeted therapies in prurigo nodularis: a systematic review and meta-analysis
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Yue Yu1, Siqi Li1, Weiwen Chen1
1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Background:
Systemic targeted therapies are reshaping treatment for prurigo nodularis (PN), but the timing of clinically meaningful benefits and the strength of supporting evidence remain unclear. We synthesized direct placebo-controlled evidence by outcome and follow-up time, distinguishing replicated phase 3 evidence from preliminary signals.
Methods:
PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched from inception to June 30, 2026, for randomized controlled trials of systemic targeted therapies for PN. Compatible outcomes were pooled separately at prespecified time points using random-effects models. The primary outcome was a ≥ 4-point reduction in weekly average Worst Itch or Peak Pruritus Numerical Rating Scale scores. Secondary outcomes included Investigator's Global Assessment (IGA) success, dual response, sleep, quality of life, psychological outcomes, and safety. Risk of bias and certainty were assessed using RoB 2 and GRADE.
Results:
Eleven trials involving 1,623 participants evaluated six therapies. Itch response favored active treatment at weeks 4 (RR 4.76, 95% CI 3.01-7.55), 12 (2.67, 1.43-5.00), 16 (3.32, 2.57-4.29), and 24 (3.09, 2.18-4.38), whereas the week 8 estimate was imprecise (1.73, 0.94-3.21). IGA success was supported from week 8 onward. Nemolizumab improved sleep response by week 4, and two phase 3 dupilumab trials showed a week 24 dual-response benefit (RR 3.98, 2.31-6.85). Treatment-emergent adverse events were modestly more frequent with active treatment (RR 1.14, 1.06-1.24), while serious adverse events and discontinuations did not clearly increase. The most robust evidence came from replicated phase 3 programs of dupilumab and nemolizumab.
Conclusion:
Replicated randomized evidence supports clinically meaningful improvements in itch and lesion outcomes with dupilumab and nemolizumab. Symptomatic benefits may emerge earlier than lesion responses, but this pattern should be interpreted cautiously because evidence across time points derives from limited, partly non-overlapping trial sets. Comparative treatment ranking is not supported, and longer-term data are needed to define rare, delayed, and agent-specific harms.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261445753, identifier CRD420261445753.