Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials

被引:152
作者
Xie, Wenhui [1 ]
Huang, Yanrong [1 ]
Xiao, Shiyu [2 ]
Sun, Xiaoying [1 ]
Fan, Yong [1 ]
Zhang, Zhuoli [1 ]
机构
[1] Peking Univ, Hosp 1, Dept Rheumatol & Clin Immunol, Beijing 100006, Peoples R China
[2] Peking Univ, Hosp 3, Dept Gastroenterol, Beijing, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
SELECTIVE JAK1 INHIBITOR; MODIFYING ANTIRHEUMATIC DRUG; NECROSIS-FACTOR INHIBITORS; INADEQUATE RESPONSE; DOUBLE-BLIND; TOFACITINIB CP-690,550; PHASE IIB; JAPANESE PATIENTS; BACKGROUND METHOTREXATE; VX-509; DECERNOTINIB;
D O I
10.1136/annrheumdis-2018-214846
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). Methods PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method. Results 26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03). Conclusion The existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.
引用
收藏
页码:1048 / 1054
页数:7
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