Baricitinib, Upadacitinib May Not Pose Same Cardiovascular Risk as Tofacitinib

Cardiovascular risks associated with tofacitinib may not extend to the Janus kinase (JAK) inhibitors baricitinib and upadacitinib, according to a paper published in the journal Clinical Rheumatology.

“Based on the available literature from trials and long-term follow-up studies of baricitinib and upadacitinib, there exists insufficient evidence to extend the warning of major adverse cardiovascular events/venous thromboembolism with tofacitinib to these drugs,” wrote corresponding author Durga Prasanna Misra and coauthors from the Sanjay Gandhi Postgraduate Institute of Medical Sciences in India.

Concerns of cardiovascular safety with JAK inhibitors stem from the ORAL Surveillance trial, which failed to demonstrate tofacitinib’s noninferiority to tumor necrosis factor-alpha inhibitors (TNFi) for risk of major adverse cardiovascular events, venous thromboembolism, or malignancy in patients 50 years and older with prevalent risk factors for cardiovascular disease, the article explained.

The US Food and Drug Administration responded to ORAL Surveillance results by issuing a boxed warning about the risk of major adverse cardiovascular events, venous thromboembolism, or malignancy with tofacitinib, as well as with baricitinib or upadacitinib, taken for inflammatory arthritis or ulcerative colitis.

Other trials and their long-term extensions have shown similar cardiovascular risk with tofacitinib and TNFi in patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritis, and inflammatory bowel diseases, according to the article. However, the authors noted that the elevated risk likely applies to specific patient populations with pre-existing risk factors for major adverse cardiovascular events and venous thromboembolism.

“Ongoing post-marketing surveillance studies of JAK inhibitors in immune-mediated inflammatory diseases should help clarify cardiovascular risk with JAK inhibitors,” the authors advised.

Reference

Misra DP, Pande G, Agarwal V. Cardiovascular risks associated with Janus kinase inhibitors: peering outside the black box. Clin Rheumatol. 2023;42(2):621-632. doi:10.1007/s10067-022-06415-5