Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety
Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety
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DOI：
10.1186/1471-2474-9-52
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发表时间：
2008-04-17
影响因子：
2.3
通讯作者：
Quintana, Antonio
中科院分区：
文献类型：
--
作者：
Alonso-Ruiz, Alberto;Pijoan, Jose Ignacio;Quintana, Antonio
背景资料：分析现有证据的有效性和安全性的抗肿瘤坏死因子α药物（英夫利西单抗，依那西普和阿达木单抗）治疗类风湿关节炎（RA）。方法：我们系统地搜索随机对照临床试验抗肿瘤坏死因子α药物治疗RA，然后进行系统评价与荟萃分析。从MEDLINE、EMBASE和科克伦图书馆数据库中检索试验。使用美国流变学学会（ACR）疗效反应标准。还评估了试验提供的安全性参数。使用组合相对风险（RR）、需要治疗的数量（NNT）和需要伤害的数量（NNH）估计积极和不良反应。结果：共纳入13个临床试验（7087例患者）。对任何推荐剂量的抗TNF α药物治疗达到治疗应答的合并RR为1.81（95% CI 1.43 - 2.29），ACR 20的NNT为5（5 - 6）。ACR 50 [5（5 - 6）]和ACR 70 [7（7 - 9）]的NNT相似。无论使用何种特定抗TNF α药物，以及何时给予高于推荐剂量的药物，总体治疗效果也相似。然而，低于推荐剂量引起低ACR 70应答（NNT 15）。在既往对MTX应答不足的患者中，抗TNF α药物加甲氨蝶呤（MTX）与MTX单药治疗的比较显示，ACR 20的NNT值为3，ACR 50为4，ACR 70为8。抗TNF α药物与安慰剂的比较显示了相似的模式。在既往对MTX无耐药性的患者中，抗TNF α药物联合MTX与单独MTX的比较显示出较低的效果。依那西普和阿达木单抗单药治疗的疗效与MTX相似。副作用在接受抗TNF α药物的患者中比对照组更常见（总体合并NNH 27）。接受英夫利西单抗治疗的患者更有可能因副作用（NNH 24）和严重副作用（NNH 31）、感染（NNH 10）和输注反应（NNH 9）而退出。接受阿达木单抗治疗的患者也更有可能因副作用（NNH 47）和注射部位反应（NNH 22）而退出。接受依那西普的患者不太可能因为副作用而退出（对照组与依那西普26相比为NNH），但更可能发生注射部位反应（NNH 5）。结论：抗TNF α药物对RA患者有效，无论给予何种药物，结果均明显相似。推荐剂量以外的剂量也是有益的。影响治疗效果的主要因素是先前对DMARD治疗的反应。依那西普或阿达木单抗治疗的效果与MTX治疗的效果无差异。已发表的依那西普的安全性特征是上级的，但没有患者接受高于推荐剂量的治疗这一事实需要解释。
Background: To analyse available evidence on the efficacy and safety of anti-TNF alpha drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA).Methods: We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNF alpha drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I-2 statistics.Results: Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNF alpha drug was 1.81 (95% CI 1.43 - 2.29) with a NNT of 5 (5 - 6) for ACR20. NNT for ACR50 [5 (5 - 6)] and ACR70 [7 (7 - 9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNF alpha drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNF alpha drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNF alpha drugs with placebo showed a similar pattern. Comparisons of anti-TNF alpha drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNF alpha drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5).Conclusion: Anti-TNF alpha drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.