Pharmacy Department, Hospital SAS La Línea and Hospital Punta Europa, Cádiz, Spain.
J Clin Pharm Ther. 2012 Jun;37(3):301-7. doi: 10.1111/j.1365-2710.2011.01292.x. Epub 2011 Aug 10.
A number of biological treatments are available for rheumatoid arthritis. They are effective some patients but their comparative efficacy is inadequately evaluated. Our aim was to compare the efficacy of adalimumab, etanercept, infliximab, abatacept, tocilizumab, golimumab and certolizumab pegol in rheumatoid arthritis, refractory to disease-modifying antirheumatic drugs (DMARDs), through a systematic review of published trials.
As there were no direct comparisons, we searched for studies with similar characteristics to identify trials with results suitable for indirect comparison. Randomized, placebo-controlled pivotal clinical trials, with reported American College of Rheumatology ACR50 data at 24/30 weeks as efficacy endpoint, approved clinical doses and patients resistant to DMARDs who had not previously received other biological treatments were included. ACR50 was defined as the primary endpoint for the indirect comparison, with ACR20 and ACR70 as secondary endpoints. When two or more trials on one same drug were available, and a combined analysis was performed when appropriate. In the indirect comparison, the Bucher adjusted method was used with etanercept as reference drug. In the equivalence study, the equivalence window was a response efficacy difference of 15% between the alternatives.
Ten trials were found suitable for detailed analysis. In the clinical trials, all the biological drugs were seen to be more effective than placebo. Indirect comparison based on the ACR50 efficacy criterion all biological treatments showed similar results within the defined equivalence Δ value. The absolute efficacy difference (reduction of absolute risk, RAR) versus etanercept being 2·6% with adalimumab, 14% with infliximab, 11·6% with abatacept, 3% with tocilizumab, 12·4% with golimumab and 6·5% with certolizumab pegol.
The biological drugs used in rheumatoid arthritis are no different in efficacy. Their therapeutic positioning depends on their relative safety and convenience profiles.
有许多生物治疗方法可用于类风湿关节炎。它们对一些患者有效，但它们的相对疗效评估不足。我们的目的是通过对已发表试验的系统评价，比较阿达木单抗、依那西普、英夫利昔单抗、阿巴西普、托珠单抗、戈利木单抗和培塞利珠单抗在难治性疾病修饰抗风湿药物（DMARDs）的类风湿关节炎患者中的疗效。
由于没有直接比较，我们搜索了具有相似特征的研究，以确定具有适合间接比较结果的试验。纳入了随机、安慰剂对照的关键临床试验，以 24/30 周时美国风湿病学会（ACR）50 缓解率作为疗效终点，报告了批准的临床剂量和未接受过其他生物治疗的 DMARDs 耐药患者。ACR50 被定义为间接比较的主要终点，ACR20 和 ACR70 为次要终点。如果一种药物有两个或多个试验，且适当时进行了联合分析。在间接比较中，使用 Bucher 调整法，以依那西普为参照药物。在等效性研究中，等效窗口是替代药物之间的疗效差异为 15%。
发现 10 项试验适合详细分析。在临床试验中，所有生物药物均优于安慰剂。基于 ACR50 疗效标准的间接比较，所有生物治疗方法在定义的等效Δ值内显示出相似的结果。与依那西普相比，阿达木单抗的绝对疗效差异（绝对风险降低，RAR）为 2.6%，英夫利昔单抗为 14%，阿巴西普为 11.6%，托珠单抗为 3%，戈利木单抗为 12.4%，培塞利珠单抗为 6.5%。
用于类风湿关节炎的生物药物在疗效上没有差异。它们的治疗定位取决于其相对安全性和便利性。
