Phase 2a randomized clinical trial of dupilumab (anti‐IL‐4Rα) for alopecia areata patients

TLDR

Treatments for extensive alopecia areata are limited, and recent evidence implicates a type‑2 T‑cell immune response in the disease. In a 24‑week, 2:1 randomized, placebo‑controlled trial, dupilumab (300 mg weekly SC) was administered to AA patients, with the primary endpoint being change in Severity of Alopecia Tool score. Dupilumab produced a statistically significant improvement in SALT score versus placebo, with 32.5 % achieving SALT30, 22.5 % SALT50, and 15 % SALT75 at week 48; baseline IgE ≥200 IU/mL predicted higher response rates (up to 53.8 % for SALT30) and no new safety signals were observed.

Abstract

Treatments for alopecia areata (AA) patients with extensive scalp hair loss are limited, and recent evidence supports a role for type 2 T-cell (Th2)-immune response in AA. Dupilumab, a monoclonal antibody inhibiting Th2 signaling, approved for type 2 diseases including atopic dermatitis, was evaluated in AA patients.Alopecia areata patients with and without concomitant atopic dermatitis were randomized 2:1 to receive weekly subcutaneous dupilumab (300 mg) or placebo for 24 weeks, followed by another 24-week dupilumab open-label phase. The primary outcome was change from baseline in the Severity of Alopecia Tool (SALT) score at week 24; secondary outcomes included a range of measures of hair regrowth.Forty and 20 patients were assigned to the dupilumab and placebo arms, respectively. At week 24, disease worsening was documented in the placebo arm, with a least-squares mean change in the SALT score of -6.5 (95% confidence-interval [CI], -10.4 to -2.6), versus a change of 2.2 (95% CI, -0.6 to 4.94) in the dupilumab arm (p < .05). After 48 weeks of dupilumab treatment, 32.5%, 22.5% and 15% of patients achieved SALT30 /SALT50 /SALT75 improvement, respectively, while in patients with baseline IgE ≥ 200 IU/ml response rates increased to 53.8%, 46.2%, and 38.5%, respectively. Moreover, baseline IgE predicts treatment response with 83% accuracy. No new safety signals were detected.This hypothesis-driven trial is the first to indicate the possible pathogenic role of the Th2 axis and Th2 targeting in AA patients. Patient selection based on baseline serum IgE levels may improve treatment results (Clinicaltrials.gov number, NCT03359356).