Dupilumab for Prurigo Nodularis: Real-World Outcomes Up to 104 Weeks from the DUPItaPN Study

Background: Prurigo nodularis (PN) is a chronic, intensely pruritic skin disorder that markedly impairs quality of life. Dupilumab, an IL-4Rα antagonist, is approved for moderate-to-severe PN, but long-term real-world evidence remains limited. Objectives: To evaluate the long-term effectiveness and safety of dupilumab in adults with PN, including those with multiple comorbidities, in a real-world multicenter setting. Methods: Clinical data were collected from 26 Italian dermatology centers. Adults with PN refractory to topical therapies and/or phototherapy, and/or prior systemic treatments who received dupilumab for a minimum treatment duration of 12 weeks were included. Outcomes routinely assessed in practice-Worst Itch Numeric Rating Scale (WI-NRS), Investigator Global Assessment for PN-Stage (IGA PN-S), Sleep NRS, Skin Pain NRS, and Dermatology Life Quality Index (DLQI)-were analyzed at baseline and weeks 12, 24, 52, 76, and 104. Main endpoints were ≥4-point WI-NRS reduction and IGA PN-S 0/1 status. Predictors of response and safety were also evaluated. Results: A total of 543 patients (mean age 65.7 years; 63.7% female) were included. Dupilumab induced rapid and sustained improvements: mean WI-NRS decreased from 8.7 to 2.7 at week 24 and to 1.7 at week 104 (p < 0.001); ≥4-point WI-NRS reduction was achieved by 86.4% and by 86.8% of patients at 24 and 104 weeks, respectively; IGA PN-S 0/1 by 62.8% and by 81.2% of patients at 24 and 104 weeks. DLQI improved from 17.4 to 2.6 (p < 0.001). Higher baseline WI-NRS predicted better outcomes, while psychiatric comorbidities and prior tricyclic antidepressant use predicted lower response. Dupilumab was well tolerated; discontinuation due to adverse events occurred in 2.9%, with no cancer progression or viral reactivation. Conclusions: Dupilumab provided sustained, clinically meaningful benefits and a favourable safety profile over 104 weeks, supporting its role as a long-term treatment for moderate-to-severe PN, including in elderly and comorbid patients.