间接比较各种生物制剂治疗传统DMARDs难治性RA

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J Clin Pharm Ther. 2011 Aug 10. doi: 10.1111/j.1365-2710.2011.01292.x. [Epub ahead of print]   Indirect comparison of biological treatments in refractory rheumatoid arthritis.   Gallego-Galisteo M, Villa-Rubio A, Alegre-Del Rey E, Márquez-Fernández E, Ramos-Báez JJ.   Source Pharmacy Department, Hospital SAS La Línea and Hospital Punta Europa Pharmacy Department, Hospital SAS La Línea Pharmacy Department, Hospital U. Puerto Real, Cádiz, Spain.   Abstract   What is known and Objective:  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. Methods:  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. Results and Discussion:  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. What is new and Conclusion:  The biological drugs used in rheumatoid arthritis are no different in efficacy. Their therapeutic positioning depends on their relative safety and convenience profiles.   PMID: 21831256

间接比较各种生物制剂治疗传统DMARDs难治性RA   Gallego-Galisteo M, et al. J Clin Pharm Ther. 2011. 提前在线发表.   目的：已有一些生物制剂用于治疗类风湿关节炎（RA）。部分患者有效，但是对于这些药物疗效的可比性尚无合适的评估。本研究旨在通过系统性评价已发表的临床试验从而比较阿达木、依那西普、英夫利昔、阿贝西普、妥昔利珠、戈利木以及舍妥利珠治疗DMARDs难治性RA的疗效。 方法：由于没有直接的比较，所以我们寻找具有相似特征的研究，以确定适于进行间接比较的试验结果。我们纳入的是随机、安慰剂对照的关键性临床试验，它们都将24或30周ACR50设为疗效观察终点，纳入的病人是DMARDs难治性的，之前未用过其它生物制剂，所用剂量也是获批准的临床剂量。ACR50被定义为间接比较的主要终点，ACR20和ACR70作为次要终点。同一药物有至少2个临床试验时，如果合适，就将数据合并后再分析。间接比较采用了布赫尔(Bucher）校正法，将依那西普作为参照药物。在等效性研究中，等效窗设为与替代品疗效相差15％。 结果与讨论：发现有10个临床试验适于本研究。临床试验发现所有生物制剂的疗效都优于安慰剂。在所定义的等效Δ值范围内，基于ACR50疗效标准的间接比较发现所有生物制剂的疗效是相似的。其它生物制剂分别与依那西普之间的绝对疗效差异（用绝对风险降低率（RAR）来表示）比较如下：阿达木为2.6％，英夫利昔为14％，阿贝西普为11.6%，妥昔利珠为3%，戈利木为12.4％，舍妥利珠为12.4%。 结论：各种生物制剂治疗RA的疗效相当，它们的临床用途定位取决于它们相对安全性和使用方便性。