Efficacy and Safety of Dupilumab in Adults with Prurigo Nodularis with or Without Atopic Comorbidities: A Subgroup Analysis from Two Randomized Phase III Clinical Trials

Background: Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by intensely pruritic papulonodular lesions. Patients with PN frequently experience comorbid atopic conditions. Dupilumab is the first approved therapy for PN, but the efficacy of dupilumab in patients with PN with or without atopic comorbidities has not been investigated. Objective: We aimed to assess the efficacy and safety of dupilumab in patients with PN with or without a history of atopic comorbidities. Methods: Randomized, double-blind, parallel-group, placebo-controlled, 24-week, phase III trials LIBERTY-PN PRIME and PRIME2 were conducted independently in 16 countries in North and South America, Europe, and Asia. Patients were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. In this pre-specified subgroup analysis of pooled data, adults with moderate-to-severe PN, inadequately controlled by topical prescription therapies, were stratified according to the presence or absence of atopic comorbidity history. Investigators assessed itch (Worst Itch Numeric Rating Scale), skin lesions (Investigator’s Global Assessment for PN Stage), and patient-reported quality of life (evaluated using the Dermatology Life Quality Index, Skin Pain Numeric Rating Scale, Hospital Anxiety and Depression Scale, and a Sleep Numeric Rating Scale). Results: Three hundred and eleven patients were randomized to dupilumab (N = 153; atopic/non-atopic n = 67/86) or placebo (N = 158; atopic/non-atopic n = 68/90). At week 24 in both the atopic and non-atopic subgroups, significantly more patients achieved clinically meaningful improvements with dupilumab treatment compared with placebo in itch (atopic: 58.2% vs 20.6%; P < 0.0001; non-atopic: 59.3% vs 17.8%; P < 0.0001), clear/almost clear skin (atopic: 52.2% vs 16.2%; P < 0.0001; non-atopic: 41.9% vs 17.8%; P = 0.0005), and concomitant itch and skin lesion improvements (atopic: 37.3% vs 7.4%; P = 0.0057; non-atopic 33.7% vs 10.0%; P = 0.007). Patients showed significant improvements in skin pain, Dermatology Life Quality Index, Hospital Anxiety and Depression Scale, and sleep, with dupilumab treatment compared with placebo, regardless of atopic history. Safety was generally consistent with the known dupilumab safety profile. Conclusions: Dupilumab significantly improved disease signs, symptoms, and health-related quality of life with similar onset time and response magnitude compared with placebo in adult patients with PN, irrespective of the presence or absence of atopic comorbidities. Clinical Trial Registration: ClinicalTrials.gov Identifiers: NCT04183335 and NCT04202679.