Le-Nguyen Alexandre, Mortuza Shamim, Hsia Cyrus C
Department of Medicine, London Health Sciences Centre, London, ON, Canada.
Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Blood Vessel Thromb Hemost. 2024 Nov 2;2(1):100035. doi: 10.1016/j.bvth.2024.100035. eCollection 2025 Feb.
Access to modern therapeutics for immune thrombocytopenia (ITP), such as thrombopoietin-receptor agonists (TPO-RAs), remains a challenge, limiting clinicians' options. We investigated azathioprine in relapsed/refractory ITP to determine its efficacy and safety, focusing on evaluating its utility in post-TPO-RA patients. We retrospectively reviewed all adult patients, aged ≥18 years, who were worked up for thrombocytopenia between 2009 and 2022 at a tertiary care center in Ontario, Canada. Only patients with ITP treated with azathioprine were included. We identified 92 patients with ITP who received azathioprine, with a mean age of 55.6 ± 22.3 years; 53 were females and 39 males, with 64 having primary ITP. The overall response rate (ORR) was 47.8% (44/92), with a sustained response rate of 77.3% (34/44) at 6 months. The median time to response was 6 weeks. Fourteen patients (31.8%) relapsed, with a median duration of response of 10 weeks. Most patients (73.9%) had documented side effects, with nausea/vomiting, infections, and myelosuppression being the most common. The majority of patients received azathioprine as third-line therapy; 6 patients after TPO-RA and 27 after splenectomy. ORR was 50.0% (3/6) and 40.7% (11/27) in each group, respectively. This is the largest retrospective study, to our knowledge, demonstrating benefit with azathioprine in relapsed/refractory ITP. Its efficacy remains consistent both after TPO-RA ( = .948) and after splenectomy ( = .259), offering clinicians a comparable drug response irrespective of prior TPO-RA exposure or splenectomy. We propose that azathioprine remains a viable option for relapsed/refractory ITP in the TPO-RA era.
获得用于免疫性血小板减少症（ITP）的现代疗法，如血小板生成素受体激动剂（TPO-RAs），仍然是一项挑战，限制了临床医生的选择。我们研究了硫唑嘌呤在复发/难治性ITP中的疗效和安全性，重点评估其在TPO-RA治疗后患者中的效用。我们回顾性分析了2009年至2022年期间在加拿大安大略省一家三级医疗中心因血小板减少症接受检查的所有≥18岁的成年患者。仅纳入接受硫唑嘌呤治疗的ITP患者。我们确定了92例接受硫唑嘌呤治疗的ITP患者，平均年龄为55.6±22.3岁；53例为女性，39例为男性，其中64例为原发性ITP。总体缓解率（ORR）为47.8%（44/92），6个月时持续缓解率为77.3%（34/44）。缓解的中位时间为6周。14例患者（31.8%）复发，缓解的中位持续时间为10周。大多数患者（73.9%）有记录的副作用，恶心/呕吐、感染和骨髓抑制最为常见。大多数患者接受硫唑嘌呤作为三线治疗；6例在TPO-RA治疗后，27例在脾切除术后。每组的ORR分别为50.0%（3/6）和40.7%（11/27）。据我们所知，这是最大的一项回顾性研究，证明硫唑嘌呤对复发/难治性ITP有益。在TPO-RA治疗后（P = 0.948）和脾切除术后（P = 0.259），其疗效均保持一致，无论之前是否接受过TPO-RA治疗或脾切除术，都为临床医生提供了相当的药物反应。我们认为，在TPO-RA时代，硫唑嘌呤仍然是复发/难治性ITP的一个可行选择。
