Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in patients with alopecia areata: efficacy and safety results of a phase II, multicentre, randomized, double-blinded, placebo-controlled trial

BACKGROUND: Alopecia areata (AA) is a common, immune-mediated inflammatory disease characterized by nonscarring hair loss. Tyrosine kinase (TYK)2 mediates signalling of select proinflammatory cytokines [e.g. interleukin (IL)-12, IL-23 and type I interferons], which may play a role in the pathogenesis of AA. OBJECTIVES: To evaluate the efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with AA. METHODS: Patients were randomized 1 : 1 : 1 to oral placebo, deucravacitinib 6 mg once daily, or deucravacitinib 6 mg twice daily. At week 24, patients randomized to placebo were rerandomized 1 : 1 to deucravacitinib 6 mg once daily or deucravacitinib 6 mg twice daily until week 52. The primary efficacy endpoint was change from baseline in Severity of Alopecia Tool (SALT) score at week 24. Secondary endpoints were proportions of patients achieving ≥ 50% reduction from baseline in SALT score (SALT 50), SALT score ≤ 20, and Alopecia Areata Investigator Global Assessment score of 0 (clear) or 1 (almost clear) with ≥ 2-point improvement from baseline at week 24. This trial was terminated following database lock at week 24, but before primary data readout, owing to a strategic decision by the sponsor and not as a result of any observed, expected or perceived efficacy or safety findings with deucravacitinib treatment. Early termination did not affect study power. RESULTS: In total, 94 patients received placebo (n = 31), deucravacitinib 6 mg once daily (n = 32), or deucravacitinib 6 mg twice daily (n = 31). Baseline disease characteristics were balanced across treatment groups. No meaningful difference in change from baseline in SALT score at week 24 was observed between the deucravacitinib and placebo groups [6 mg once daily: adjusted mean difference 1.5, 95% confidence interval (CI) -6.2 to 9.2, P = 0.701; 6 mg twice daily: 8.2, 95% CI 0.2-16.2, P = 0.045]. Similarly, no differences were observed for any secondary endpoint. No new safety signals were identified. CONCLUSIONS: This trial did not meet the efficacy endpoints and TYK2 inhibition by deucravacitinib may not play a major role in hair regrowth in patients with AA. The safety of deucravacitinib in patients with AA was consistent with the known safety profile of this TYK2 inhibitor.