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 SALT 30 /SALT 50 /SALT 75 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).

Upadacitinib improved alopecia areata in a patient with atopic dermatitis: A case report

“… 1 , 2 , 3 For these reasons, the use of dupilumab, a fully monoclonal antibody directed against the IL‐4 receptor α subunit and approved for the treatment of adults and adolescents with moderate‐to‐severe AD, has recently been proposed for the treatment of AA in patients with or without AD. 1 , 4 However, its effectiveness in AA treatment is controversial. 1 Conversely, Janus kinase inhibitors (JAKs) 1 seem to constitute a new therapeutic option in the management of both AD and AA.…”

“…Since the failure of first‐line therapies and the concomitance of the two diseases we decided to start treatment with dupilumab. 1 , 4 At the 4‐month follow‐up visit, despite the marked improvement in the body skin lesions, the patients showed erythemato‐squamous lesions in the head and neck area, associated to itching and burning and resistant to treatment with potent topical corticosteroids and antifungal medication. A paradoxical “red face” due to dupilumab was diagnosed and dupilumab was stopped.…”

Clinical, trichoscopic and in vivo reflectance confocal microscopy evaluation of alopecia areata in atopic dermatitis patients treated with dupilumab

“…In patients with baseline levels of IgE ≥ 200 IU/mL, the response rates increased to 53.8%, 46.2% and 38.5% respectively. 9 We retrospectively investigated the efficacy of dupilumab in 10 adult patients [Six females and four males; mean age 43.71 AE 8.22 years] affected by both AA and AD, attending to our department from April 2018 to May 2021. Dupilumab was administered at scheduled dosage for AD (300 mg every 2 weeks, after an initial loading dose of 600 mg).…”

“…Moreover, our patients were treated with dupilumab at scheduled dosage for AD instead of 300 mg weekly used in phase IIa trial. 9 More controlled studies are needed to assess the effectiveness of dupilumab for AA (Fig 1).…”

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

“…We read with interest the results of Guttman‐Yasky et al's paper utilizing dupilumab in the treatment of longstanding alopecia areata 1 …”