The efficacy of inhibiting tumour necrosis factor α and interleukin 1 in patients with rheumatoid arthritis:: a meta-analysis and adjusted indirect comparisons
The efficacy of inhibiting tumour necrosis factor α and interleukin 1 in patients with rheumatoid arthritis:: a meta-analysis and adjusted indirect comparisons
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DOI：
10.1093/rheumatology/kem072
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发表时间：
2007-07-01
期刊：
影响因子：
5.5
通讯作者：
Brennan, A.
中科院分区：
文献类型：
--
作者：
Nixon, R.;Bansback, N.;Brennan, A.
客观的。抑制细胞因子肿瘤坏死因子 α (TNF α) 和白细胞介素 1 (IL-1) 治疗类风湿性关节炎的新疗法，在针对早期和晚期疾病以及不同严重程度组的多项临床试验中，已证明相对安慰剂和甲氨蝶呤 (MTX) 具有临床效果。由于没有直接比较目前可用的治疗方法（依那西普、阿达木单抗、英夫利昔单抗或阿那白滞素）的头对头随机对照试验，我们进行了一项荟萃分析，调整研究特征之间的差异，并允许在治疗方法之间进行间接比较。对文献进行系统回顾，纳入了 13 项细胞因子拮抗剂试验。他们报告了 6 个月或更长时间内美国风湿病学会 (ACR) 反应标准的主要结果。荟萃分析方法用于量化相对治疗效果，使用 6 个月时 ACR20 或 ACR50 反应的对数比值比，同时调整研究水平变量。结果。在每项试验中，与安慰剂或 MTX 相比，细胞因子治疗均有效。对于每种治疗，联合使用 MTX 可以改善疗效。对研究水平变量进行调整后，我们发现 TNFa 拮抗剂比阿那白滞素更有效（P < 0.05）。三种 TNF α 拮抗剂之间的间接比较表明功效没有差异。使用不同统计模型结构的敏感性分析证实了这些结果。结论。当感兴趣的结果是 6 个月时 ACR20 或 ACR50 反应的概率时，我们发现：（i）IL-1 拮抗剂阿那白滞素治疗优于安慰剂； (ii) 对于每种治疗，联合使用 MTX 可以提高缓解的可能性； (iii)用任何TNFα拮抗剂治疗均优于用IL-1拮抗剂阿那白滞素治疗； (iv) TNFu拮抗剂类别中的所有药物彼此没有不同。
Objective. New treatments that inhibit the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments.Methods. Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables.Results. In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNFa antagonists to be more efficacious compared with anakinra (P< 0.05). Indirect comparisons between the three TNF alpha antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results.Conclusion. When the out.pome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNF alpha antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNFu antagonist class are no different from each other.