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21-05-2019 | Rheumatology | News | Article

Short-term JAK inhibitor use not linked to increased CV risk

medwireNews: Rheumatoid arthritis (RA) patients receiving Janus kinase (JAK) inhibitors may not be at increased risk for cardiovascular events (CVEs) in the short term, suggests a meta-analysis of randomized controlled trials (RCTs) comparing the active agents with placebo.

The authors did not observe a dose effect for either tofacitinib or upadacitinib, but note that the 2 mg dose of baricitinib was associated with a significantly lower risk for CVEs than the 4 mg dose.

In light of these findings as well as recent research pointing to an elevated risk for pulmonary embolism with tofacitinib 10 mg versus anti-tumor necrosis factor therapy, the team says “continuous postmarketing surveillance of emerging data is urgently needed to comprehensively clarify the association of [JAK inhibitors] and cardiovascular outcomes in [an] RA population.”

As reported in the Annals of the Rheumatic Diseases, the meta-analysis included data on 11,799 adult patients enrolled in 26 double-blind RCTs that compared one or two doses of a JAK inhibitor – most commonly tofacitinib (n=10), baricitinib (n=6), and upadacitinib (n=4) – with placebo.

Pooled analysis of 25 trials showed no evidence of increased CVE risk with JAK inhibitors relative to placebo, either overall (nonsignificant odds ratio [OR]=1.04) or when considering each drug individually.

There was also no significantly raised risk for major adverse cardiovascular events (MACE) with JAK inhibitor treatment, again either overall or individually, versus placebo.

And although there appeared to be trend for a higher incidence of venous thromboembolism (VTE) with JAK inhibitors than placebo, this association was not statistically significant. Interestingly, tofacitinib appeared to be associated with a lower risk for VTE compared with placebo, whereas baricitinib and upadacitinib tended to raise the risk, although again these relationships did not reach statistical significance.

Data from 18 trials were available for the analysis of dose-dependent effects, and showed no significant differences between the higher and lower doses of tofacitinib (5 vs 10 mg) or upadacitinib (15 vs 30 mg) in terms of either all CVEs, MACE, or VTE.

However, the risk for all CVEs appeared to be significantly lower with the 2 mg than 4 mg dose of baricitinib (OR=0.19). The 2 mg dose was also associated with a lower incidence of MACE (OR=0.20) and VTE (OR=0.23) than the 4 mg dose, but these associations were not statistically significant.

Researcher Zhuoli Zhang, from Peking University First Hospital in Beijing, China, and colleagues note several limitations of their analysis, including the fact that the randomized controlled phase of the trials was “relatively short” (12–104 weeks).

On the whole, however, these results indicate “a ‘neutral’ role of short-term [JAK inhibitor] treatment in cardiovascular outcomes,” they conclude.

The team continues: “Further investigations are urgently needed to confirm long-term cardiovascular safety of [JAK inhibitors], especially at the higher dose.”

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Ann Rheum Dis 2019; doi:10.1136/annrheumdis-2018-214846