Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
Semin Arthritis Rheum. 2019 Jun;48(6):958-966. doi: 10.1016/j.semarthrit.2018.10.002. Epub 2018 Oct 9.
To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).
MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.
The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.
Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.
评估甲氨蝶呤（MTX）联合已获批的生物制剂与生物单药治疗类风湿关节炎（RA）患者的疗效和安全性。
检索 MEDLINE、EMBASE、CENTRAL 及其他来源，评估生物制剂联合 MTX 与单药治疗相比的随机试验。主要结局为 ACR50 和因不良反应（AE）停药的患者数量。采用随机效应模型进行 meta 分析，计算风险比和 95%置信区间，并采用 GRADE 方法评估估计值的可信度。
纳入 16 项试验（4965 例患者），包括所有获批用于 RA 的生物制剂，但不包括阿那白滞素和依那西普。与生物单药治疗相比，MTX 联合生物制剂治疗 6 个月后，总体应答（即 ACR50）的可能性高 32%（1.32[1.20-1.45]；P<0.001），相当于每 100 例患者中多 11 例（7-16 例）；中质量证据。与生物单药治疗相比，MTX 联合使用导致 AE 而停药的可能性高 20%（1.21[0.97-1.50]；P=0.09），相当于每 100 例患者中多 1 例（0-3 例）；中质量证据。
随机试验提供了中质量证据，表明在 RA 患者处方生物制剂时，与生物单药治疗相比，MTX 联合使用具有有利的获益-风险平衡，但从绝对数值来看，只有 7-16 例患者在接受这种联合治疗 6 个月后会出现 ACR50 应答。
