Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Clin Ther. 2010 Oct;32(11):1855-70. doi: 10.1016/j.clinthera.2010.10.011.
Abatacept, a soluble human fusion protein that selectively modulates the costimulatory signal required for full T-cell activation, is approved for the treatment of rheumatoid arthritis (RA) in the United States, Canada, and the European Union. Because rare but serious adverse effects have been associated with biologic therapies, it is important to assess the safety profiles of these agents on an ongoing basis.
This article reviews current evidence on the safety profile of abatacept in patients with RA.
PubMed/MEDLINE was searched for clinical trials of abatacept using the terms abatacept OR CTLA4Ig, rheumatoid arthritis, and safety. Searches of abstracts presented at the 2007-2009 annual meetings of the American College of Rheumatology, European League Against Rheumatism, and Canadian Rheumatology Association were also conducted. Reports from clinical trials of at least 6 months' duration that evaluated abatacept in adults with RA were included in the review.
Seven placebo-controlled trials and 1 open- label trial were included in the review, as were the long-term extensions of 5 of the studies and an integrated safety analysis. Abatacept added to methotrexate had an acceptable safety profile in patients with RA who had an inadequate response to methotrexate or other traditional disease-modifying antirheumatic drugs, or who failed to respond to treatment with anti-tumor necrosis factor agents. In the 5 core trials, discontinuations due to adverse events ranged from 1.9% to 8.7% of abatacept recipients and 0.9% to 4.3% of placebo recipients. In the integrated safety analysis, serious infections were reported in 3.0% of abatacept recipients and 1.9% of placebo recipients; the corresponding rates of malignancies were 3.7% and 2.9%. No additional safety concerns emerged during up to 7 years of exposure in the long-term extension studies. Antibodies to abatacept developed in ≤3% of patients, with no association found between immunogenicity and adverse events.
Based on the evidence reviewed, abatacept had an acceptable safety profile and was well tolerated in patients with RA.
阿巴西普是一种可溶性人融合蛋白，可选择性调节完全 T 细胞激活所需的共刺激信号，已获美国、加拿大和欧盟批准用于治疗类风湿关节炎（RA）。由于生物疗法会引起罕见但严重的不良反应，因此持续评估这些药物的安全性非常重要。
本文综述了阿巴西普治疗 RA 患者的安全性概况。
使用 abatacept 或 CTLA4Ig、类风湿关节炎和安全性等术语，对 PubMed/MEDLINE 进行检索，以查找阿巴西普的临床试验。还对 2007-2009 年美国风湿病学会、欧洲抗风湿病联盟和加拿大风湿病学会年会的摘要进行了检索。综述纳入了至少 6 个月疗程、评估阿巴西普治疗 RA 成人患者的临床试验报告。
综述纳入了 7 项安慰剂对照试验和 1 项开放标签试验，以及其中 5 项研究的长期扩展研究和综合安全性分析。阿巴西普联合甲氨蝶呤治疗对甲氨蝶呤治疗应答不足或其他传统疾病修饰抗风湿药物治疗应答不佳，或对肿瘤坏死因子拮抗剂治疗无应答的 RA 患者具有可接受的安全性。在 5 项核心试验中，因不良事件而停药的阿巴西普组患者为 1.9%至 8.7%，安慰剂组为 0.9%至 4.3%。在综合安全性分析中，阿巴西普组报告了 3.0%的严重感染和 1.9%的安慰剂组报告了严重感染；相应的恶性肿瘤发生率分别为 3.7%和 2.9%。在长期扩展研究中，最长 7 年的暴露期间未出现新的安全性问题。≤3%的患者产生了针对阿巴西普的抗体，且免疫原性与不良事件之间无关联。
根据综述证据，阿巴西普治疗 RA 患者的安全性良好，耐受情况良好。
