A multicenter, open-label, uncontrolled, single-arm phase 2 study of tirabrutinib, an oral Bruton’s tyrosine kinase inhibitor, in pemphigus

Abstract

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Immunopathology and Immunotherapy of Inflammatory Skin Diseases

“…Preclinical data showed Dsg3 CAAR T cells specifically target and lyse Dsg3-specific B cells, thus preserving non-pathogenic B cells ( 78 ). Rilzabrutinib and tirabrutinib, oral Bruton’s tyrosine kinase inhibitors that inhibit B-cell activation, were found to decrease the dose of systemic corticosteroid needed and reduce disease activity in pemphigus vulgaris in a phase 2 trial ( 79 80 ). In addition, efgartigimod and ALXN1830, FcRn blocking antibodies, showed an early onset of clinical improvement in pemphigus patients in phase 2 trials ( 81 82 ).…”

Translational autoimmunity in pemphigus and the role of novel Bruton tyrosine kinase inhibitors

“…Tirabrutinib hydrochloride (ONO/GS-4059), also known as tirabrutinib, is a broad-range oral BTK inhibitor, which has recently been licensed in Japan for the treatment of plasma cell lymphoma, primary lymphoma of the central nervous system, and Waldenstrom macroglobulinemia [ 3 ]. Tirabrutinib inhibits increase in culprit protein levels in lupus-prone animal and human B-cells and reduces stimulation-induced IgG production (unpublished findings) [ 47 ].…”

“…This molecule is designed to inhibit the IgG autoantibody-mediated signaling pathway involved in the pathogenesis of pemphigus pathogenesis and provide an alternative therapy for resistant pemphigus. Yamagamia et al [ 3 ] conducted a phase II trial to evaluate the safety and efficacy of tirabrutinib in patients with refractory pemphigus. Sixteen patients were included in this study.…”

“…Pemphigus vulgaris (PV), which causes agonizing oral erosions, and pemphigus foliaceus (PF), which causes skin lesions, are the two primary categories. A few types of this disease can be lethal if left untreated [ 3 ].…”

Immunotherapy for Pemphigus: Present and Future

“…Additionally, Jun Yamagami et al investigated the efficacy and safety of tirabrutinib, another BTK inhibitor, in patients with refractory pemphigus in a multicenter, open-label, uncontrolled, single-arm phase II study. They reported that treatment with tirabrutinib enabled remission and reduced oral corticosteroids over time without significant safety concerns in patients with refractory pemphigus ( 57 ). Interestingly, another BTK inhibitor (PRN473) has been reported with a good response in canine pemphigus foliaceus (PF) ( 58 ).…”