上海交通大学医学院仁济医院戈之铮团队研究了沙利度胺治疗小肠血管发育不良所致复发性出血的疗效与安全性。2023年11月1日出版的《新英格兰医学杂志》发表了这项成果。

小肠复发性出血占胃肠道出血病例的5%至10%，仍是一个治疗挑战。沙利度胺已被评估用于治疗小肠血管发育不良（SIA）引起的复发性出血，但缺乏验证性试验。

研究组进行了一项多中心、双盲、随机、安慰剂对照试验，用于研究沙利度胺治疗SIA复发性出血的疗效和安全性。符合条件的SIA复发性出血（前一年至少有四次出血）患者被随机分配接受每日口服剂量为100 mg或50 mg的沙利度胺或安慰剂治疗4个月。患者在4个月的治疗期结束后至少随访1年。主要终点是有效缓解，即与治疗前一年相比，沙利度胺治疗结束后一年发生的出血次数至少减少50%。关键次要终点是停止出血而不再次出血、输血、因出血住院、出血持续时间和血红蛋白水平。

总体而言，150名患者接受了随机分组：51名患者接受100 mg沙利度胺，49名患者接受50 mg沙利度胺，50名患者接受安慰剂。100 mg沙利度胺组、50 mg沙利度胺组和安慰剂组中有效缓解的患者百分比分别为68.6%、51.0%和16.0%（三组同时比较P＜0.001）。次要终点的分析结果支持主要终点的结果。总体而言，沙利度胺组的不良事件比安慰剂组更常见；具体事件包括便秘、嗜睡、四肢麻木、外周水肿、头晕和肝酶水平升高。

研究结果表明，在这项安慰剂对照试验中，沙利度胺治疗可减少SIA复发性出血患者的出血。

附：英文原文

Title: Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia

Author: Huimin Chen, Shan Wu, Mingyu Tang, Ran Zhao, Qingwei Zhang, Zihao Dai, Yunjie Gao, Shiming Yang, Zhaoshen Li, Yiqi Du, Aiming Yang, Liang Zhong, Lungen Lu, Leiming Xu, Xizhong Shen, Side Liu, Jie Zhong, Xiaobo Li, Hong Lu, Hua Xiong, Yufeng Shen, Haiying Chen, Shuai Gong, Hanbing Xue, Zhizheng Ge

Issue&Volume: 2023-11-01

Abstract:

Background

Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking.

Methods

We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels.

Results

Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels.

Conclusions

In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA.

DOI: 10.1056/NEJMoa2303706

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2303706