Dupilumab for prurigo nodularis: real-world outcomes up to 104 weeks from the Dupilumab Italian Prurigo Nodularis (DUPItaPN) study

Background Prurigo nodularis (PN) is a chronic, intensely pruritic skin disorder that markedly impairs quality of life. Dupilumab, an interleukin-4R alpha 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 multicentre setting. Methods Clinical data were collected from 26 Italian dermatology centres [the Dupilumab Italian Prurigo Nodularis (DUPItaPN) study]. 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 (WI) Numeric Rating Scale (NRS) (WI-NRS), Investigator Global Assessment for PN-Stage (IGA PN-S), Sleep-NRS, Skin Pain-NRS and Dermatology Life Quality Index (DLQI) - were analysed 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 In total, 543 patients [mean age 65.7 (SD 15.8) years; 63.7% (346/543) female] were included. Dupilumab induced rapid and sustained improvements: mean WI-NRS decreased from 8.69 (SD 1.41) to 2.67 (SD 2.59) at week 24 and to 1.72 (SD 2.44) at week 104 (P < 0.001); >= 4-point WI-NRS reduction was achieved by 78.6% (408/519) and by 86.9% (258/297) of patients at 24 and 104 weeks, respectively; and IGA PN-S 0/1 achieved by 62.8% (326/519) and 81.1% (241/297) of patients at 24 and 104 weeks. DLQI improved from 17.40 (SD 6.94) to 2.57 (SD 4.89) (P < 0.001). Higher baseline WI-NRS predicted better outcomes, whereas psychiatric comorbidities and prior tricyclic antidepressant use predicted lower response. Dupilumab was well tolerated; discontinuation because of adverse events occurred in 2.9% (16/543), 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 older adults and patients with comorbidities.