Maxwell Lara, Singh Jasvinder A
Institute of Population Health, University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N 6N5.
Cochrane Database Syst Rev. 2009 Oct 7;2009(4):CD007277. doi: 10.1002/14651858.CD007277.pub2.
Abatacept inhibits the co-stimulation of T cells and disrupts the inflammatory chain of events that leads to joint inflammation, pain, and damage in rheumatoid arthritis.
To assess the efficacy and safety of abatacept in reducing disease activity, pain, and improving function in people with rheumatoid arthritis.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (from 1966), EMBASE (from 1980), ACP Journal Club (from 2000), and Biosis Previews (from 1990) in March 2007 and December 2008. We contacted authors of included studies and the abatacept manufacturer.
Randomized controlled trials comparing abatacept alone, or in combination with disease-modifying anti-rheumatic drugs (DMARDs) or biologics, to placebo or other DMARDs or biologics in patients with moderate to severe rheumatoid arthritis.
Two authors independently assessed search results and risk of bias, and extracted data. We obtained adverse event data from trials, long-term extension studies, and regulatory agencies.
Seven trials with 2908 patients were included. Compared with placebo, patients in the abatacept group were 2.2 times more likely to achieve an ACR 50 response at one year (RR 2.21, 95% confidence interval (CI) 1.73 to 2.82) with a 21% (95% CI 16% to 27%) absolute risk difference between groups. The number needed to treat to achieve an ACR 50 response was 5 (95% CI 4 to 7). Significant improvements in physical function and a reduction in disease activity and pain were found in abatacept-treated patients compared to placebo. One RCT found abatacept significantly slowed the radiographic progression of joint damage at 12 months compared to placebo, although it is not clear what the clinical relevance of this difference may be. There may be a risk of attrition bias. Total adverse events were greater in the abatacept group (RR 1.05, 95% CI 1.01 to 1.08). Other harm outcomes were not significant with the exception of a greater number of serious infections at 12 months in the abatacept group (Peto odds ratio 1.91 (95% CI 1.07 to 3.42). Serious adverse events were increased when abatacept was given in combination with other biologics (RR 2.30, 95% CI 1.15 to 4.62).
AUTHORS' CONCLUSIONS: There is moderate-level evidence that abatacept is efficacious and safe in the treatment of rheumatoid arthritis. Abatacept should not be used in combination with other biologics to treat rheumatoid arthritis. The withdrawal and toxicity profile appears acceptable at the present time but further long-term studies and post-marketing surveillance are required to assess harms and sustained efficacy.
阿巴西普普抑制T细胞共刺激，破坏类风湿关节炎中导致关节炎症、疼痛和损伤的炎症事件链。
评估阿巴西普在降低类风湿关节炎患者疾病活动度、疼痛及改善功能方面的疗效和安全性。
我们于2007年3月和2008年12月检索了Cochrane对照试验中心注册库（CENTRAL）（《Cochrane图书馆》2007年第1期）、MEDLINE（1966年起）、EMBASE（1980年起）、《美国内科医师学会杂志俱乐部》（2000年起）和《生物学文摘》（1990年起）。我们联系了纳入研究的作者及阿巴西普制造商。
将阿巴西普单药治疗、或与改善病情抗风湿药（DMARDs）或生物制剂联合使用，与安慰剂或其他DMARDs或生物制剂进行比较的中度至重度类风湿关节炎患者的随机对照试验。
两位作者独立评估检索结果和偏倚风险，并提取数据。我们从试验、长期延长期研究及监管机构获取不良事件数据。
纳入了7项试验，共2908例患者。与安慰剂相比，阿巴西普组患者在1年时达到美国风湿病学会（ACR）50反应的可能性高2.2倍（相对危险度2.21，95%置信区间（CI）1.73至2.82），组间绝对危险度差异为21%（95%CI 16%至27%）。达到ACR50反应所需治疗人数为5（95%CI 4至7）。与安慰剂相比，接受阿巴西普治疗的患者身体功能有显著改善，疾病活动度和疼痛减轻。一项随机对照试验发现，与安慰剂相比，阿巴西普在12个月时显著减缓了关节损伤的影像学进展，尽管尚不清楚这种差异的临床相关性如何。可能存在失访偏倚风险。阿巴西普组的总不良事件更多（相对危险度1.05，95%CI 1.01至1.08）。除阿巴西普组在12个月时严重感染数量较多外（Peto比值比1.91（95%CI 1.07至3.42）），其他不良结局不显著。阿巴西普与其他生物制剂联合使用时严重不良事件增加（相对危险度2.30，95%CI 1.15至4.62）。
有中等强度证据表明阿巴西普治疗类风湿关节炎有效且安全。阿巴西普不应与其他生物制剂联合用于治疗类风湿关节炎。目前撤药和毒性情况似乎可以接受，但需要进一步的长期研究和上市后监测来评估危害和持续疗效。
