Yamagami Jun, Ujiie Hideyuki, Aoyama Yumi, Ishii Norito, Tateishi Chiharu, Ishiko Akira, Ichijima Tomoki, Hagihara Shunsuke, Hashimoto Koji, Amagai Masayuki
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
J Dermatol Sci. 2021 Sep;103(3):135-142. doi: 10.1016/j.jdermsci.2021.07.002. Epub 2021 Jul 6.
The treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling.
We investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus.
This was a multicenter, open-label, single-arm phase 2 study of Japanese patients with refractory pemphigus receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent.
In total, 16 patients were evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 6.6 %-43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A relationship with tirabrutinib was ruled out for all serious AEs and Grade ≥3 AEs.
Treatment with tirabrutinib enabled remission and reduced oral corticosteroid exposure over time and did not result in any major safety concerns in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new treatment option for patients with refractory pemphigus.
天疱疮的治疗基于全身使用糖皮质激素及辅助治疗，但一些患者对传统疗法耐药。替拉布替尼是一种高度选择性的口服布鲁顿酪氨酸激酶抑制剂，可能通过抑制B细胞信号传导在临床上有效治疗天疱疮。
我们研究了替拉布替尼治疗难治性天疱疮患者的疗效和安全性。
这是一项针对接受口服糖皮质激素和辅助治疗的难治性天疱疮日本患者的多中心、开放标签、单臂2期研究。患者餐后口服替拉布替尼80mg，每日一次，共52周。替拉布替尼治疗16周后，将糖皮质激素剂量逐渐减至相当于泼尼松龙≤10mg/天。
总共评估了16例患者（平均年龄52.5岁；50%为男性）。治疗24周后的完全缓解率（主要终点）为18.8%（3/16；95%置信区间，6.6%-43.0%）。到第52周时，8例患者（50.0%）实现完全缓解，10例患者（62.5%）实现缓解。在52周的治疗期间，泼尼松龙平均剂量从17.03mg/天降至7.65mg/天。不良事件（AE）和药物不良反应的发生率分别为87.5%和43.8%。所有严重AE和≥3级AE均排除与替拉布替尼的关系。
替拉布替尼治疗可实现缓解，并随着时间的推移减少口服糖皮质激素的用量，且在难治性天疱疮患者中未导致任何重大安全问题。因此，口服替拉布替尼可能为难治性天疱疮患者提供一种新的治疗选择。
