508 - Dupilumab treatment normalizes intraepidermal nerve fiber density in patients with moderate-to-severe AD

Abstract

Abstract Introduction Chronic pruritus is a characteristic of atopic dermatitis (AD), contributing to poor quality of life in patients. Alterations in neuroanatomy and neuroarchitecture associated with pruritus secondary to AD are not fully understood. Objectives To explore the role of dupilumab treatment effect on epidermal neuroanatomy by quantifying intraepidermal nerve fiber density (IENFD). Method DIFFERENSTAD (NCT04823130) was an open-label, exploratory study that enrolled patients ≥ 18 years old with moderate-to-severe AD, pruritus lasting > 6 weeks, and Worst Itch Numerical Rating Scale (WI-NRS) ≥ 4, and matched healthy controls. Patients with AD received dupilumab 300 mg every 2 weeks for 16 weeks. Skin biopsies were obtained from patients’ lesional skin at baseline and localization-matched skin at Week 17 (end of treatment, EoT) and from healthy controls. The primary endpoint, IENFD, was defined as number of nerve fibers crossing the basement membrane per millimeter. Results 31 patients with moderate-to-severe AD and 10 matched controls were enrolled. IENFD in patients with AD significantly increased from baseline to EoT (mean [SE]: 7.7 [1.3] at baseline vs 12.1 [2.0] at EoT for patients with AD; P = 0.0017), to levels comparable with the control group (mean [SE]: 12.4 [2.3]; P for control group vs EoT in patients with AD = 0.9374). Mean (SE) Eczema Area and Severity Index (EASI) total score and WI-NRS in dupilumab-treated patients were 22.5 (1.5) and 8.5 (0.3) at baseline, and 5.1 (1.1) and 3.1 (0.5) at EoT (both change from baseline P < 0.0001), respectively. The safety profile was consistent with the known safety profile for dupilumab. Conclusions Dupilumab treatment significantly increased IENFD to levels similar to those of healthy subjects, suggesting restored neuroanatomy in patients with moderate-to-severe AD. Dupilumab also significantly improved clinical signs and pruritus symptoms of AD.