School of Pharmaceutical Sciences, University of Campinas, R. Candido Portinari, 200, Cidade Universitária Zeferino Vaz, Campinas, SP, 13083-871, Brazil.
University of Sorocaba, Rod. Raposo Tavares, Km 92.5, Sorocaba, SP, 18023-000, Brazil.
Rheumatol Int. 2020 Dec;40(12):1949-1959. doi: 10.1007/s00296-020-04651-z. Epub 2020 Jul 24.
The effects of dose reduction or spacing of all types of biologics in rheumatoid arthritis has not been consistently assessed in systematic reviews. We aimed to assess the effects of biologics reduction compared with dose maintenance in patients with rheumatoid arthritis in low disease activity or remission. We performed a systematic review with meta-analysis according to a previously registered protocol (PROSPERO registration: CRD42017069080); and searched MEDLINE, Embase, Scopus, Cochrane Library and trial registers up to July, 2020. Two researchers selected, extracted and assessed the risk of bias of controlled trials that randomized patients to reduction/spacing or dose maintenance of biologics. Low disease activity, disability and other clinically important outcomes were summarized in random effect meta-analyses. We rated the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation approach. We included ten studies (n = 1331 patients), which assessed reduction or spacing of abatacept, adalimumab, certolizumab pegol, etanercept, or tocilizumab. Risk of bias was high in over half of trials, mainly due to lack of blinding. No statistically significant difference was found in low disease activity (RR = 0.90; 95% CI 0.78-1.04; I = 60%, very low certainty), and other outcomes. Subgroup analysis of blinded studies led to homogeneous results, which remained heterogeneous in open-label studies. Reduction or spacing biologics did not affect disease activity and other important outcome. Changes in the doses regimen should consider patient preferences, considering the low certainty of evidence.
在系统性评价中，尚未一致评估减少或延长所有类型生物制剂剂量在低疾病活动度或缓解期类风湿关节炎患者中的效果。我们旨在评估与维持剂量相比，减少生物制剂剂量在低疾病活动度或缓解期类风湿关节炎患者中的效果。我们根据先前注册的方案（PROSPERO 注册：CRD42017069080）进行了系统评价和荟萃分析；并检索了 MEDLINE、Embase、Scopus、Cochrane 图书馆和试验登记处，检索截止日期为 2020 年 7 月。两名研究人员选择、提取和评估了将患者随机分配到减少/延长或维持生物制剂剂量的对照试验的偏倚风险。使用随机效应荟萃分析总结了低疾病活动度、残疾和其他重要临床结局。我们根据推荐评估、制定和评价方法（Grading of Recommendations Assessment, Development, and Evaluation approach）对证据的确定性进行评级。我们纳入了十项研究（n=1331 名患者），评估了阿巴西普、阿达木单抗、certolizumab pegol、依那西普或托珠单抗的减少或延长剂量。超过一半的试验存在高偏倚风险，主要是因为缺乏盲法。在低疾病活动度（RR=0.90；95%CI 0.78-1.04；I=60%，极低确定性）和其他结局方面，未发现统计学显著差异。盲法研究的亚组分析结果一致，但开放标签研究结果仍存在异质性。减少或延长生物制剂不会影响疾病活动度和其他重要结局。改变剂量方案应考虑患者的偏好，同时考虑到证据的低确定性。
