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Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials
  1. Wenhui Xie1,
  2. Yanrong Huang1,
  3. Shiyu Xiao2,
  4. Xiaoying Sun1,
  5. Yong Fan1,
  6. Zhuoli Zhang1
  1. 1 Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China
  2. 2 Department of Gastroenterology, Peking University Third Hospital, Beijing, China
  1. Correspondence to Professor Zhuoli Zhang, Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100006, China; zhuoli.zhang{at}126.com

Abstract

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.

  • rheumatoid arthritis
  • Janus kinase inhibitors
  • cardiovascular events
  • randomised controlled trials
  • meta-analysis
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors ZZ conceived the study, participated in its design and coordination, and critically revised the manuscript. WX had full access to all of the data collection, analysis, interpretation and drafted the manuscript. YH, XS, YF and SX were study investigators and contributed to the process of data collection. All authors read and approved the final manuscript.

  • Funding This work was supported by the National Natural Science Foundation of China (81771740), the subproject (2010CB529103) under the National Science Technology Pillar Program of China (973 Program) (2010CB529100), the Capital Health Research and Development of Special Fund Program (2011-4021-03), the Peking University Clinical Research Program (PUCRP201305) and Beijing Natural Science Foundation (7184251).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available in a public, open access repository.

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