Pharmacy Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Pharmacy Department, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain.
Pharmacotherapy. 2020 Dec;40(12):1248-1264. doi: 10.1002/phar.2472. Epub 2020 Nov 16.
To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, LILACS, and Google Scholar databases to identify controlled observational and clinical trials reporting on adverse effects in patients treated with oral tofacitinib or baricitinib up to July 2020. The outcome measure was occurrence of VTE events. We analyzed 59 studies involving 14,335 patients treated with tofacitinib or baricitinib and 11,612 patients who received another active drug or placebo. The meta-analysis showed an odds ratio (OR) for VTE events of 0.29 (95% confidence interval [CI] = 0.10-0.84) overall for tofacitinib based on data from 10 clinical trials with 15 treatment arms; similar ORs were observed for the 10 mg/d dose (OR = 0.18; 95% CI = 0.02-1.60) and the 20 mg/d dose (OR = 0.19; 95% CI = 0.04-0.91). The ORs for VTE events for baricitinib were 3.39 (95% CI = 0.82-14.04) overall, 3.05 (95% CI = 0.12-75.43) for 2 mg, 3.64 (95% CI = 0.59-22.46) for 4 mg, and 3.0 (95% CI = 0.12-76.49) for 7 mg. The indirect meta-analysis comparing tofacitinib with baricitinib (10 clinical trials with 15 treatment arms) showed an OR for VTE events of 0.086 (95% CI = 0.02-0.51) for tofacitinib and a superior safety profile for VTE events. In the meta-regression analysis (19 clinical trials with 21 treatment arms), the effect was 0.02 (95% CI = -0.04 to 0.08) for tofacitinib and -0.01 (95% CI = -1.29 to 1.26 for baricitinib. Plotting of the data for tofacitinib showed that VTE risk increased with high doses. The effect, however, was less than 1 for the 10-mg and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. Tofacitinib is not associated with an increased risk of VTE and has a superior safety profile to baricitinib in this respect. Tofacitinib may exert a protective effect against VTE.
进行系统评价和荟萃分析，以调查托法替尼和巴瑞替尼对静脉血栓栓塞（VTE）风险的影响。检索PubMed、EMBASE、Web of Science、Scopus、ClinicalTrials.gov、LILACS 和 Google Scholar 数据库，以确定截至 2020 年 7 月报告口服托法替尼或巴瑞替尼治疗患者不良事件的对照观察性和临床试验。结局指标为 VTE 事件的发生。我们分析了 59 项研究，共纳入 14335 例接受托法替尼或巴瑞替尼治疗的患者和 11612 例接受另一种活性药物或安慰剂治疗的患者。荟萃分析显示，托法替尼治疗 VTE 事件的优势比（OR）总体为 0.29（95%置信区间[CI]：0.10-0.84），基于 10 项临床试验（15 个治疗臂）的数据；对于 10mg/d 剂量（OR=0.18；95%CI=0.02-1.60）和 20mg/d 剂量（OR=0.19；95%CI=0.04-0.91），也观察到了类似的 OR。巴瑞替尼治疗 VTE 事件的 OR 总体为 3.39（95%CI=0.82-14.04），2mg 为 3.05（95%CI=0.12-75.43），4mg 为 3.64（95%CI=0.59-22.46），7mg 为 3.0（95%CI=0.12-76.49）。比较托法替尼和巴瑞替尼的间接荟萃分析（10 项临床试验，15 个治疗臂）显示，托法替尼治疗 VTE 事件的 OR 为 0.086（95%CI=0.02-0.51），VTE 事件的安全性状况更好。在荟萃回归分析（19 项临床试验，21 个治疗臂）中，托法替尼的效应为 0.02（95%CI=-0.04 至 0.08），巴瑞替尼的效应为-0.01（95%CI=-1.29 至 1.26）。托法替尼的数据图显示，随着剂量的增加，VTE 风险增加。然而，对于 10mg 和 20mg 剂量，其效果小于 1，表明具有保护作用。在巴瑞替尼中未观察到这种作用。托法替尼与 VTE 风险增加无关，在这方面具有优于巴瑞替尼的安全性。托法替尼可能对 VTE 有保护作用。
