Bruton’s tyrosine kinase (BTK) enhances BCR-stimulated proliferation, costimulatory molecule expression, and antibody production in B cells. Tirabrutinib is a highly selective oral BTK inhibitor that is expected to inhibit the immunoglobulin G autoantibody-mediated mechanism that plays a central role in the pathophysiology of pemphigus. The aim of this study was to investigate the efficacy and safety of tirabrutinib in patients with refractory pemphigus. In this multicenter, open-label, single-arm phase 2 study, patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. In total, 16 patients were evaluated. The complete remission (CR) rate after 24 weeks of treatment (primary endpoint) was 18.8% (3/16 patients). The cumulative CR rate and cumulative remission rate at 52 weeks of treatment were 50.0% and 62.5%, respectively. Control of disease activity rates were 37.5%, 60%, 78.6%, and 92.9% at weeks 4, 12, 24, and 52, respectively. During the 52 weeks of tirabrutinib administration, decreases in pemphigus disease area index score, anti-desmoglein 1 and 3 autoantibody levels, and oral corticosteroid exposure were observed. One patient (6.3%) relapsed. The incidence of adverse events (AEs) and serious AEs were 87.5% and 18.8%, respectively. No grade ≥4 AEs were reported. The patients in this study showed favorable outcomes in response to the treatment with tirabrutinib and did not result in any major safety concerns. Thus, tirabrutinib may be a new treatment option for patients with refractory pemphigus.

ESDR037 - Efficacy and safety of tirabrutinib, highly selective Bruton’s tyrosine kinase inhibitor, for oral treatment of pemphigus: a multicenter, open-label, uncontrolled, single-arm phase 2 study

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING