Oral Bruton’s tyrosine kinase inhibitor shows therapeutic potential in refractory pemphigus

B-cell signalling suppression with tirabrutinib appears to promote remission in patients with refractory pemphigus, as shown in a phase II trial. Furthermore, treatment has reduced oral corticosteroid exposure over time without any major safety concerns.

The open-label, single-arm phase II trial involved 16 Japanese patients (mean age 52.5 years; 50 percent male) with refractory pemphigus who were dosed with oral tirabrutinib 80 mg, administered postprandially once daily for 52 weeks.

All patients had been receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. After 16 weeks of treatment with tirabrutinib, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent.

The primary endpoint of complete remission after 24 weeks of treatment occurred in three patients, corresponding to a rate of 18.8 percent (95 percent confidence interval [CI], 6.6–43.0). By the end of treatment, at week 52, eight patients (50.0 percent) had achieved complete remission and 10 patients (62.5 percent) attained remission.

The mean prednisolone dose decreased from 17.03 mg/day at baseline to 7.65 mg/day at week 52. The incidence rate of adverse events (AEs) was 87.5 percent, while the rate of adverse drug reactions was 43.8 percent. Tirabrutinib showed no association with all serious AEs and grade ≥3 AEs.

The findings suggest that oral tirabrutinib, a highly selective oral Bruton’s tyrosine kinase inhibitor, may represent a new treatment option for patients with refractory pemphigus.