Clinical Trial Comparison of Dupilumab and Nemolizumab for Prurigo Nodularis FDA-Approved Biologic Therapy Selection in Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic, pruritic skin disorder characterized by significant morbidity and historically limited treatment options. The recent approval of biologic therapies has rapidly changed the treatment landscape, with dupilumab and nemolizumab now Food and Drug Administration (FDA)-approved for PN. This article provides a clinically relevant overview of completed randomized trials, highlighting differences in efficacy, timing of response, and symptom targets. Data were extracted from six compound randomized clinical trials (two dupilumab trials and four nemolizumab trials) identified on ClinicalTrials.gov through January 2025. Across phase 3 studies, dupilumab demonstrated sustained reductions in itch severity and lesional disease, with approximately 58-60% of patients achieving a ≥ 4-point improvement in Worst Itch Numeric Rating Scale (WI-NRS) scores and 45-48% achieving Investigator Global Assessment for Prurigo Nodularis-Stage (IGA PN-S) success by week 24. Nemolizumab showed a more rapid onset of antipruritic effect, with 41-56% of patients achieving a ≥ 4-point improvement in Peak Pruritus Numeric Rating Scale (PP-NRS) scores as early as week 4, along with clinically meaningful improvements in sleep disturbance by week 16. Both therapies demonstrated manageable safety profiles, with predominantly mild to moderate adverse events and low rates of serious adverse events, although nemolizumab was associated with higher overall rates of mild to moderate adverse events. These findings suggest that dupilumab may offer greater lesional clearance at later time points, whereas nemolizumab may provide faster itch relief and less sleep disturbance. These findings support a phenotype-guided approach to biologic selection while highlighting the need for further comparative studies.