Department of HEOR and Strategic Market Access.
J Manag Care Spec Pharm. 2015 May;21(5):409-23. doi: 10.18553/jmcp.2015.21.5.409.
Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs.
To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR).
Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses.
With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain.
Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy.
鉴于有许多可供选择的生物治疗方案和其他新型疾病修饰抗风湿药物（DMARDs）可用于治疗类风湿关节炎（RA）患者，临床医生在选择最佳治疗方案时面临着越来越大的挑战。生物制剂通常与传统的 DMARDs 联合使用，主要是甲氨蝶呤（MTX），但一些生物制剂和托法替尼（在本文中统称为新型 DMARDs）已被证明作为单一疗法也同样有效。在实际实践中，大约三分之一接受生物制剂治疗的 RA 患者接受单一疗法，主要是由于对 MTX 不耐受或不依从。然而，关于新型 DMARDs 与联合治疗相比的单一疗法有效性的数据有限。
比较在对传统 DMARDs（DMARD-IR）反应不足的 RA 患者中，批准的新型 DMARDs 作为单一疗法或与 MTX 联合治疗在 24 周时与美国风湿病学会（ACR）反应的差异，这些新型 DMARDs 已被证明作为单一疗法或与 MTX 联合治疗在 DMARD-IR RA 患者中是有效的。
通过对文献的系统回顾，我们确定了评估批准的新型 DMARDs 作为单一疗法或与 MTX 联合治疗在 DMARD-IR RA 患者中的随机对照试验。确定了 28 项 RCTs，评估了阿巴西普、阿那白滞素、阿达木单抗、依那西普、戈利木单抗、英夫利昔单抗、托西珠单抗或托法替尼。提取并通过贝叶斯网络荟萃分析结合了 24 周时的 ACR 反应。
除了阿那白滞素联合 MTX 的疗效较差外，大多数新型 DMARDs 与 MTX 联合使用时，表现出相似的 ACR 反应。当新型 DMARDs 作为单一疗法时，与抗 TNF 药物（aTNF）或托法替尼相比，托西珠单抗的 ACR20/50/70 反应更大。此外，托西珠单抗联合 MTX 的 ACR20/50/70 反应与托西珠单抗单药治疗相似（间接比较的优势比[OR]为 1.08，95%可信区间[CrI]为 0.40-2.84；OR 为 1.24，CrI 为 0.44-3.61；OR 为 0.95，CrI 为 0.33-2.72），而 aTNF 联合 MTX 的反应大于 aTNF 单药治疗（OR 为 2.41，CrI 为 0.51-11.61；OR 为 2.85，CrI 为 0.51-17.67；OR 为 1.28，CrI 为 0.21-8.42）。托法替尼联合 MTX 与托法替尼单药治疗的间接比较的相对疗效估计非常不确定。
结果表明，在与 MTX 联合使用时，大多数可用的新型 DMARDs 在 DMARD-IR 患者中具有相似的疗效水平。然而，作为单一疗法，托西珠单抗的 ACR 反应高于 aTNF 或托法替尼。托西珠单抗联合 MTX 的 ACR 反应与托西珠单抗单药治疗相似，而 aTNF 联合 MTX 与 aTNF 单药治疗相比，具有更高的 ACR 反应。
