(236) Dupilumab monotherapy vs topical corticosteroids in prurigo nodularis: impact on signs and symptoms in the PRIME/PRIME2 studies

Background: : Prurigo nodularis (PN) is a chronic inflammatory disease that substantially impacts quality of life. Topical corticosteroids (TCS) are commonly used but often fail to provide adequate control. Dupilumab is the first advanced therapy approved for PN in the USA, EU, and Japan.

Objective: : To demonstrate the value of dupilumab monotherapy compared to medium-potency TCS.

Methods: : LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were randomized, double-blind, 24-week, Phase 3 trials of dupilumab in adult patients with moderate-to-severe PN. Patients were randomized to dupilumab 300 mg every 2 weeks or matched placebo, for 24 weeks. Patients on a stable regimen of low-to-moderate potency TCS or topical calcineurin inhibitors before screening could continue use during the trial. Patients were stratified into those receiving dupilumab without stable TCS use (dupilumab monotherapy) and those on placebo with stable TCS use (TCS monotherapy). Stable TCS use was defined as application for ≥5 of 7 days before Day 1, maintaining the same medicine and dose throughout treatment. These patients were assessed for: ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) and Investigator’s Global Assessment of PN Stage (IGA PN-S) up to Week 24.

Results: : Of the 311 patients in the pooled PRIME/PRIME2 studies, 62 patients in the dupilumab group did not have stable TCS use, and 91 patients in the placebo group had stable TCS use. At Week 4, a significantly greater proportion of patients receiving dupilumab monotherapy vs TCS monotherapy achieved a ≥4-point reduction in WI-NRS (16.4% vs 3.4%; P=0.0057) and this proportion increased through Week 24 (63.8% vs 23.2%; P< 0.0001). Similarly, a significantly greater proportion of patients receiving dupilumab monotherapy vs TCS monotherapy achieved IGA PN-S of 0/1 by Week 4 (9.8% vs 1.2%; P=0.02) through Week 24 (49.2% vs 15.3%; P< 0.0001). Overall safety was generally consistent with the known safety profile of dupilumab.

Conclusions: : A significant number of patients receiving dupilumab monotherapy achieved clinically meaningful improvements in itch (63.8%) and lesions (49.2%) vs those treated with TCS alone by Week 24, with improvements as early as Week 4. The data demonstrate the clinical benefit of dupilumab monotherapy which may inform clinical management and patient expectations.

Sponsorship:: Sanofi and Regeneron Pharmaceuticals Inc.