Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Department of Clinical Sciences, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
Vet Dermatol. 2020 Oct;31(5):410-e110. doi: 10.1111/vde.12878. Epub 2020 Aug 17.
Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is one of the most common canine autoimmune skin diseases.
To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF.
Four privately owned dogs.
Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC).
All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17-33 mg/kg. Anti-DSC-1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog.
BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.
布鲁顿酪氨酸激酶（BTK）在 B 细胞信号转导中起重要作用。BTK 抑制剂（BTKi）已在人类自身免疫性疾病中显示出疗效。犬落叶型天疱疮（cPF）是最常见的犬自身免疫性皮肤病之一。
确定 BTKi PRN1008 治疗 cPF 的安全性和疗效。
4 只私人拥有的狗。
4 只被诊断为 PF 的狗接受了 BTKi PRN1008 治疗。初始剂量约为 15mg/kg ，每日一次，如果反应不足，则增加至每日两次。治疗持续 20 周，尝试减少至隔日一次。通过全血细胞计数、血清生化分析和尿液分析监测狗，并使用经验证的人类天疱疮疾病活动指数（cPDAI）的改良版本进行评估。在治疗前后进行血清抗桥粒芯糖蛋白 1（DSC-1）和桥粒芯糖蛋白 1（DSG-1）免疫球蛋白（IgG）滴度检测。测量外周血单核细胞（PBMC）中与靶标结合的药物。
所有 4 只狗在治疗的前两周内病变和 cPDAI 评分均有所下降。3 只狗继续改善，并在 20 周时达到近乎完全缓解，此时 3 个反应被认为“良好”，1 个反应“一般”。最终的每日剂量范围为 17-33mg/kg。一只狗的抗 DSC-1 IgG 滴度显著下降，两只狗的抗 DSC-1 IgG 滴度不可检测，一只狗的抗 DSC-1 IgG 滴度无法解释。没有狗检测到针对 DSG1 的 IgG。一只狗出现了一种可能的不良反应事件。
BTKi PRN1008 单药治疗可能对某些 cPF 病例有一定的疗效。
