In patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (Jakinibs), there are no short-term significant changes in cardiovascular risk, according to study results published in the Annals of the Rheumatic Diseases. However, the researchers noted that post-marketing data is still needed to determine their long-term cardiovascular safety, especially at higher doses.

The researchers searched PubMed, Embase, and Cochrane library for randomized controlled trials from inception through October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACES)/venous thromboembolism events (VTEs). The researchers used the Mantel-Haenszel fixed-effect method to calculate odds ratios [ORs] and 95% confidence intervals. The researchers identified a total of 26 randomized controlled trials that included 11,799 participants.

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The results indicated that there was no significant difference in the risk for CVEs after using any Jakinibs (OR, 1.04; 95% CI, 0.61 to 1.76; P =.89). When they looked at specific Jakinibs, they did not find any significant differences in the risk for CVEs with tofacitinib (OR, 0.63; 95% CI, 0.26 to 1.54; P =.31), baricitinib (OR, 1.21; 95% CI, 0.51 to 2.83; P =.66), upadacitinib (OR, 3.29; 95% CI, 0.59 to 18.44; P =.18), peficitinib (OR, 0.43; 95% CI, 0.07 to 2.54; P =.35) or decernotinib (OR, 1.12; 95% CI, 0.13 to 10.11; P =.92).

Patients undergoing Jakinibs treatment did not have a significant difference in the risk for MACES (OR, 0.80; 95% CI, 0.36 to 1.75; P =.57) or VTEs (OR, 1.16; 95% CI, 0.48 to 2.81; P =.74).


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The researchers did not find any dose-dependent impact of Jakinibs on the risk for all CVEs, MACEs, or VTEs with tofacitinib (5 mg vs 10 mg) or upadacitinib (15 mg vs 30 mg). However, baricitinib 2 mg was found to be safer than 4 mg in all CVEs incidence (OR, 0.19; 95% CI, 0.04 to 0.88; P =.03).

“Continuous post-marketing surveillance of emerging data is urgently needed to comprehensively clarify the association of Jakinibs and cardiovascular outcomes in RA population,” the researchers wrote.

Reference

Xie W, Huang Y, Xiao S, Sun X, Fan Y, Zhang Z. Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials. Ann Rheum Dis. 2019;78:1048-1054.