Pharmacy Department, Puerto Real Universitary Hospital, Cadiz, Spain.
Pharmacy Department, Miguel Servet Universitary Hospital, Zaragoza, Spain.
J Clin Pharm Ther. 2019 Jun;44(3):384-396. doi: 10.1111/jcpt.12795. Epub 2019 Feb 6.
Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments.
We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta-analysis (NMA) was performed using Bayesian approaches and the fixed-effects model.
Twenty-seven randomized clinical trials (RCTs) that met the pre-established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab-m, anakinra-m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab-m was better than anakinra-m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept-m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra-m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept-m; however, they displayed ETA with certolizumab-m, except for adalimumab and anakinra-m.
All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.
类风湿关节炎（RA）是一种主要以关节炎症和疼痛为特征的自身免疫性疾病。托法替尼是一种最近被批准用于 RA 治疗的口服药物；它抑制 Janus 蛋白激酶（JAK），当常规 DMARD 没有引发反应时，可减轻 RA 症状。本研究旨在比较生物 DMARD 在 RA 患者中单独使用或与甲氨蝶呤联合使用的疗效，并比较这些治疗方法。
我们检索了截至 2017 年 6 月发表的文献，评估了在对常规 DMARD 反应不足且对生物 DMARD 无经验的 RA 患者中，生物 DMARD 治疗的疗效和安全性，考虑 ACR50 作为疗效变量。计算了每种药物联合的优势比（OR）和 95%置信区间（CI），并将这些参数转换为对替代药物的反应差异，以评估替代药物的有效性。为了评估这些药物具有等效疗效的可能性，还进行了等效治疗替代（ETA）。使用贝叶斯方法和固定效应模型进行了网络荟萃分析（NMA）。
确定了 27 项符合既定标准的随机临床试验（RCT）。除了 certolizumab、golimumab-m、anakinra-m 和 adalimumab 单药治疗外，生物 DMARD 的 95%CI 高于安慰剂，没有甲氨蝶呤。这些 DMARD 与安慰剂相比，除了 etanercept、certolizumab、tocilizumab 和 golimumab 外，都表现出了更好的疗效。certolizumab-m 优于 anakinra-m 和 adalimumab，单独使用 tocilizumab 或与甲氨蝶呤联合使用优于 adalimumab。与其他生物 DMARD 相比，etanercept-m 产生的反应差异更大，除了 adalimumab 和 anakinra-m 产生的结果较差外，其他生物 DMARD 反应更均匀。除了 adalimumab 和 anakinra-m 外，没有一种生物 DMARD 与 etanercept-m 有 ETA，但与 certolizumab-m 有 ETA，除了 adalimumab 和 anakinra-m 外。
在对生物 DMARD 无经验的患者中，所有与甲氨蝶呤联合使用的生物 DMARD（除了 etanercept、anakinra、certolizumab 和没有甲氨蝶呤的 tocilizumab）在第 24 周时均显示 ACR50 的 ETA。虽然比较结果的高不确定性使得无法确认这种药物的疗效增加，但 etanercept 显示出更大的反应差异。
