Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Department of Rheumatology and Immunology, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
Rheumatology (Oxford). 2024 Jan 4;63(1):79-84. doi: 10.1093/rheumatology/kead160.
CTD-related immune thrombocytopenia (CTD-ITP) represents an unmet medical need because the drugs that are available are only partly effective and have considerable side-effects. The aim of this study was to assess the efficacy and safety of sirolimus in refractory CTD-ITP patients.
We did a single-arm, open-label, pilot study of sirolimus in patients with CTD-ITP unresponsive to, or intolerant of, conventional medications. Patients received oral sirolimus for 6 months at a starting dose of 0.5-1 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/ml. The primary efficacy end point was changes in platelet count, and overall response assessed according to the ITP International Working Group Criteria. Safety outcomes included tolerance as assessed by the occurrence of common side-effects.
Between November 2020 and February 2022, 12 consecutively hospitalized patients with refractory CTD-ITP were enrolled and prospectively followed. Of these, six patients (50%) achieved complete response, two (16.7%) achieved partial response, and four (33.3%) were no response under therapy. Three of four patients with primary Sjögren's syndrome and two of three patients with systemic lupus erythematosus achieved overall response. One of two patients with overlapping Sjögren's syndrome and systemic lupus erythematosus achieved complete response at 6 months. No severe drug-related toxicities were observed.
Our results do support sirolimus as an alternative regimen for refractory CTD-ITP patients, including systemic lupus erythematosus and primary SS.
CTD-ITP 代表了一种未满足的医学需求,因为现有的药物仅部分有效且具有相当大的副作用。本研究旨在评估西罗莫司在难治性 CTD-ITP 患者中的疗效和安全性。
我们进行了一项单臂、开放标签、西罗莫司治疗对常规药物治疗无反应或不耐受的 CTD-ITP 患者的初步研究。患者接受西罗莫司口服治疗,起始剂量为 0.5-1mg/天,根据耐受性和维持 6-15ng/ml 的治疗范围调整剂量。主要疗效终点为血小板计数的变化,根据 ITP 国际工作组标准评估总体反应。安全性结果包括通过常见副作用的发生评估耐受性。
2020 年 11 月至 2022 年 2 月,连续收治了 12 例难治性 CTD-ITP 住院患者并进行了前瞻性随访。其中,6 例(50%)患者达到完全缓解,2 例(16.7%)患者达到部分缓解,4 例(33.3%)患者治疗后无反应。4 例原发性干燥综合征患者中有 3 例和 3 例系统性红斑狼疮患者中有 2 例达到总体反应。2 例重叠干燥综合征和系统性红斑狼疮患者中有 1 例在 6 个月时达到完全缓解。未观察到严重的药物相关毒性。
我们的结果确实支持西罗莫司作为难治性 CTD-ITP 患者的替代治疗方案,包括系统性红斑狼疮和原发性干燥综合征。