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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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).

Keywords: IgE; Th2; alopecia areata; atopic dermatitis; dupilumab.

Figure 1. Least-squares Mean Change in the Severity of Alopecia Tool (SALT) Score (Baseline – Post Treatment) (A) and Responder Rates Over the Duration of the Study (Until Week 72) (B-D).

Red, blue and purple represent drug, placebo arms, and dupilumab after placebo (open-label), respectively. */**/*** denote significant (P<0.05/0.01/0.001 respectively) difference in the dupilumab arm as compared to placebo treatment (black), dupilumab open-label versus placebo treatment in the placebo arm (gray), and change from baseline at each time point in the dupilumab arm (red) and in the open-label phase of the placebo arm (purple). In (A), solid lines represent patients treated with dupilumab, dotted lines represent patients that were assessed on weeks 60 and 72 but were no longer treated with dupilumab after week 48.

Figure 2. Scalp Pictures of Four Patients in the Drug Arm.

A-D and H-K show scalp hair at baseline, week 24, week 48, and week 72 visits in patients continuing treatment after week 48. E-G and L-N show scalp hair at baseline, week 24, and week 48 visits.

Figure 3. Pearson Correlation of Changes in SALT Score with Baseline IgE Levels (A,B), Baseline Total Serum IgE as a Predictor of Response to Dupilumab (C), and Responder Rates Based on IgE Levels at Baseline (D-F).

Correlation of patients in the dupilumab arm after completing 48 weeks of treatment (A), correlation of all patients treated with 24 weeks of dupilumab together (i.e., those completing week 24 in the drug arm with those completing week 24 to week 48 in the placebo arm, after switching to dupilumab) (B). False discovery rate (FDR)<0.05 for both A and B. Receiver operating characteristic area under the curve (AUC) analysis utilizing IgE as a predictor of SALT₅₀ response at week 24 (C), with IgE levels able to predict response in 83% of AA dupilumab-treated patients. Responder (SALT_30/50/75) rates in the entire drug arm, along with lines depicting only patients with high or low IgE (threshold: 200IU/ml) in the drug arm (D-F). SALT, Severity of Alopecia Tool. */**/*** denote significant (P<0.05/0.01/0.001 respectively) difference in responder rates in patients with high versus low IgE at baseline.