33993 Oral difelikefalin improves itch and quality of life in subjects with itch-dominant atopic dermatitis: Subgroup analysis of a randomized, phase 2 study

Abstract

Background: In atopic dermatitis (AD), pruritus and lesional severity are not well correlated. Patients with limited body surface area (BSA) involvement may have intense pruritus not fully addressed by available therapies. Itch-dominant AD impairs quality of life (QoL). We report efficacy of oral difelikefalin (DFK), a kappa-opioid receptor agonist, for pruritus, QoL, and sleep disturbance in subjects with BSA <10% receiving DFK 0.5 mg or placebo (PBO) for 12 weeks. Methods: Phase 2, randomized, PBO-controlled study (NCT04018027) in adults with AD (Investigator Global Assessment ≥2, BSA ≤30%) and moderate-to-severe pruritus (Itch Numerical Rating Scale [I-NRS] ≥5.0) inadequately controlled by topical therapy. Results: Subjects (DFK, n = 82; PBO, n = 79) had high disease burden (mean I-NRS, 7.7, 7.6, respectively; DLQI, 10.6, 12.0) despite limited Eczema Area and Severity Index (mean, 4.0, 3.7). At week 12, a significantly greater proportion of subjects receiving DFK achieved ≥4-point I-NRS improvement versus PBO (33% vs 19%; P < .05; OR = 2.1). Greater proportions of subjects receiving DFK achieved responses at week 12 on the Patient Global Impression of Change (“much improved” or “very much improved”: 50% vs 35%; OR = 1.8); Sleep NRS (≥3-point improvement: 57% vs 47%; OR = 1.5); and Dermatology Life Quality Index (≥4-point improvement: 62% vs 50%; OR = 1.6). Conclusion: Itch-dominant AD is associated with impaired QoL despite mild-to-moderate lesional severity, suggesting that itch reduction should be a primary treatment goal in these patients. DFK showed clinically meaningful improvements in itch intensity, sleep, and QoL and may address the unmet need for a safe, effective antipruritic treatment in itch-dominant AD.