类风湿关节炎患者使用生物制剂和靶向药物的严重不良反应风险：一项系统评价和荟萃分析
Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis.
作者信息
Tarp Simon, Eric Furst Daniel, Boers Maarten, Luta George, Bliddal Henning, Tarp Ulrik, Heller Asmussen Karsten, Brock Birgitte, Dossing Anna, Schjødt Jørgensen Tanja, Thirstrup Steffen, Christensen Robin
机构信息
Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
David Geffen School of Medicine, University of California Los Angeles, CA.
出版信息
Rheumatology (Oxford). 2017 Mar 1;56(3):417-425. doi: 10.1093/rheumatology/kew442.
OBJECTIVES
To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.
METHODS
Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).
RESULTS
A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.
CONCLUSION
Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42014014842.
目的
确定目前已批准的10种用于类风湿关节炎（RA）的生物制剂和靶向合成改善病情抗风湿药（b/ts-DMARDs）在严重不良反应方面可能存在的差异。
方法
通过对文献数据库、试验注册库和监管机构网站进行系统综述，确定已批准的用于RA的b/ts-DMARDs的随机试验。采用混合效应泊松回归模型进行网状荟萃分析，根据发生事件的受试者与观察人年数的关系，计算10种药物中每种药物与对照（即未接受b/ts-DMARD治疗）之间严重不良事件（SAEs）和死亡的发生率比值。采用推荐分级评估、制定和评价方法（GRADE）评估估计值的可信度。
结果
共纳入117项试验（47615例患者）。与阿巴西普相比，赛妥珠单抗的SAEs更常见（发生率比值=1.58，95%CI：1.18，2.14），阿达木单抗（1.36，95%CI：1.02，1.81），依那西普（1.60，95%CI：1.18，2.17），戈利木单抗（1.45，95%CI：1.00，2.08），利妥昔单抗（1.63，95%CI：1.16，2.30），托法替布（1.44，95%CI：1.03，2.02）和对照（1.45，95%CI：1.13，1.87）；与阿巴西普相比，托珠单抗的SAEs也更常见（1.30，95%CI：1.03，1.65），依那西普（1.31，95%CI：1.04，1.67）和利妥昔单抗（1.34，95%CI：1.01，1.78）。其他比较均无统计学意义。考虑研究持续时间后，证实了我们在长达6个月治疗期的研究结果，但在长期治疗（6 - 24个月）中未得到证实。未发现b/ts-DMARDs与对照之间在死亡率上存在差异。基于GRADE方法，由于缺乏直接比较试验以及间接估计的不精确性，对估计值的可信度较低。
结论
尽管对估计值的可信度较低，但我们的分析发现SAEs发生率存在潜在差异。我们的数据表明，在现有药物之间做出决策时应谨慎。
系统综述注册号
PROSPERO CRD42014014842。
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