Rates of venous thromboembolism (VTE) were also similar (adjusted HR 1.1, 95% CI 0.7-1.6) in the study of nearly 16,000 rheumatoid arthritis patients, the researchers reported in Annals of the Rheumatic Diseases.
An examination of French national registry data revealed that patients taking Janus kinase (JAK) inhibitors for rheumatoid arthritis had cardiovascular results comparable to those of patients taking the TNF inhibitor adalimumab (Humira).
According to Lea Hoisnard, MD, of Assistance Publique-Hôpitaux de Paris in France, and colleagues, after adjusting for potential confounding factors—the most notable of which was higher methotrexate use in adalimumab users—the hazard ratio for major adverse cardiovascular events (MACE) with JAK inhibitors versus adalimumab was 1.0 (95% CI 0.7-1.5).
In contrast to adalimumab, the most widely used step-up therapy for rheumatoid arthritis, the findings provide “reassuring data about the risk of MACEs and VTEs” with JAK inhibitors, according to Hoisnard and colleagues. JAK inhibitors, such as tofacitinib (Xeljanz) and baricitinib (Olumiant), now carry boxed warnings about these side effects on their labels. Arthritis medications in the JAK inhibitor class are only prescribed to specific patients who have not responded to or are unable to tolerate one or more TNF blockers.
Previous studies have linked increased rates of VTE and other cardiovascular events with the use of JAK inhibitors. ORAL Surveillance, an FDA-mandated safety study on tofacitinib, revealed in January that there was a numerically higher MACE risk with JAK inhibitors, but it did not achieve statistical significance, which prevented tofacitinib from receiving approval.
Hoisnard and colleagues looked at French national health records in order to gain more knowledge because of this uncertainty.
From July 2017 to May 2021, the researchers identified 8,481 individuals with rheumatoid arthritis who began using tofacitinib or baricitinib and matched them with 7,354 peers who began on adalimumab. The JAK inhibitors’ median follow-up was 440 days while adalimumab’s was 344 days. With a mean age of 59 years in the JAK inhibitor cohort and 55 years in the adalimumab cohort, patients fit the profile of those adding a targeted immunomodulator. Roughly three-quarters of both groups were female.
The majority of patients in both groups had at least one cardiovascular event risk factor. Methotrexate use was still more prevalent among these individuals at enrollment (21% vs 11%), even though more people in the adalimumab group had used it in the past (58% vs 51%). JAK inhibitor users were more likely to have taken a biological medication in the past (67% vs. 39%). Myocardial infarction and ischemic stroke together make up MACE.
The researchers found a numerical disadvantage for JAK inhibitor users when taking into account a wider range of cardiovascular problems, such as transient ischemic attack and unstable angina, which was not statistically significant after adjusting for methotrexate use and other factors. Although this did not achieve statistical significance and did not apply to MACE, there was a suggestion that older patients with cardiovascular risk factors did suffer an elevated risk with JAK inhibitors: those 50 years and older with at least one conventional risk factor were 50% more likely to experience VTE than adalimumab users.
Only a small number of MACE and VTE events occurred in these subgroups, according to Hoisnard and colleagues, who emphasised that the study was underpowered for these analyses. The absence of information on crucial factors like family history and the study’s brief follow-up were further drawbacks. Hoisnard and colleagues noted that it’s also possible that the registry’s payment data did not adequately reflect patients’ actual prescription usage.
Parvathy Sukumaran 
