The Lupus and Vasculitis Clinic VRR 4242, Copenhagen University Hospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark.
Clinical Pharmacology Unit, Zealand University Hospital, Roskilde, Munkesøvej 18, 4000 Roskilde, Denmark.
Int J Mol Sci. 2019 Sep 5;20(18):4350. doi: 10.3390/ijms20184350.
The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars).
五种已批准的肿瘤坏死因子抑制剂（TNFi：英夫利昔单抗、依那西普、阿达木单抗、赛妥珠单抗和戈利木单抗）在类风湿关节炎（RA）中的关节破坏效果已在随机对照试验（RCT）中与甲氨蝶呤（MTX）进行了比较，但尚未直接相互比较，也未与未接受其他治疗的安慰剂对照进行比较。本分析比较了标准剂量、高剂量和低剂量 TNFi 对 RA 放射学关节破坏的影响，并通过贝叶斯网络荟萃分析将这些影响与 MTX 和安慰剂联系起来。我们确定了 31 项关于 TNFi 对关节破坏影响的 RCT 和 5 项具有对照的 RCT，这些 RCT 可以在网络中将未接受其他治疗的安慰剂对照与 TNFi 治疗间接联系起来。与安慰剂的以前未测试的比较是为了不仅估计相对于另一种药物的效果，而且还估计可达到的绝对效果。与安慰剂相比，英夫利昔单抗、依那西普、阿达木单抗、赛妥珠单抗和戈利木单抗对关节破坏具有高度显著的抑制作用，单药治疗时每年约为 0.9%，与 MTX 联合使用时每年约为 1.2%。尽管明显优于 MTX 和安慰剂，但戈利木单抗似乎不如其余的 TNFi。原始参考药物（Remicade、Enbrel）和几乎相同的复制药物（生物类似物）之间没有差异。
