For IBD, No Cardiovascular Risk Difference Between JAK, TNF Inhibitors

ORLANDO — Major cardiovascular event risk in patients with inflammatory bowel disease (IBD) was no greater with Janus kinase (JAK) inhibitors than with tumor necrosis factor (TNF) inhibitors, according to a retrospective single-center study.

In a matched analysis, rates of major adverse cardiac events were 3.10% for patients taking the JAK inhibitors tofacitinib (Xeljanz) or upadacitinib (Rinvoq) versus 4.27% for those taking TNF inhibitors infliximab (Remicade) or adalimumab (Humira; adjusted odds ratio [aOR] 0.70, 95% CI 0.43-1.16, P=0.17), Himsikhar Khataniar, MD, of Allegheny General Hospital in Pittsburgh, reported at the Advances in Inflammatory Bowel Diseases annual meeting.

Despite the effectiveness of JAK inhibitors for IBD, the authors noted that concerns about cardiovascular safety have circulated since the 2022 ORAL Surveillance study found a higher risk of major adverse cardiovascular events in rheumatoid arthritis (RA) patients who took tofacitinib compared with those on TNF inhibitors.

“We wanted to see if this would hold true in the case of an IBD population or not,” Khataniar told MedPage Today. He said it’s not clear why excess cardiovascular risk would show up in RA patients but not in IBD patients.

“These diseases might be autoimmune, but their genetic components might be different,” Khataniar said. “But most importantly, drug interactions [may be present] because many rheumatoid arthritis patients are on methotrexate, so methotrexate may be one of the causes.” While his team did not look closely at methotrexate interactions, they did make sure to balance methotrexate use between groups during their matching.

Their study was conducted only at a single academic hospital, so Khataniar said he hopes that drug companies will conduct larger head-to-head trials to see how long-term outcomes compare between JAK inhibitor and TNF inhibitor medications. For now, he suggested these findings might offer some reassurance, noting that one physician who dropped by the poster said he regularly has to reassure his patients that it’s OK to try a JAK inhibitor.

“Many of the parents are kind of afraid because this [ORAL Surveillance study] spread like wildfire,” Khataniar said.

Khataniar and his colleagues conducted a retrospective cohort analysis using the TriNetX database’s U.S. Collaborative Network for patients ages 50 and older who had IBD, had at least one cardiovascular risk factor, and were treated with either a JAK inhibitor or TNF inhibitor.

The primary outcome was incidence of any major adverse cardiac event, including acute myocardial infarction, heart failure, or stroke, within 1 year. Secondary outcomes included all-cause mortality, venous thromboembolism, malignancy, and herpes zoster.

The researchers used 1:1 propensity score matching for patients’ demographics, comorbidities, and previous IBD medications, including use of methotrexate and steroids. They also conducted a subgroup analysis by JAK inhibitor type and age: 50-64 years or 65 and older.

The 1,050 patients in the JAK inhibitor cohort, 41.5% of whom were male and 77.2% of whom were white, were an average of 61 years old, and 41.3% had Crohn’s disease. The 9,124 patients in the TNF inhibitor cohort, 43.9% of whom were male and 76.7% of whom were white, were also an average of 61 years old, and 39.1% had Crohn’s.

Risk was similar between the JAK and TNF inhibitor groups for individual components of the major adverse cardiovascular event endpoint:

• Acute myocardial infarction: 1.08% vs 1.53% (aOR 0.92, 95% CI 0.41-2.03, P=0.84)
• Acute heart failure: 1.17% vs 0.9% (aOR 0.76, 95% CI 0.33-1.75, P=0.52)
• Stroke: 1.08% vs 1.44% (aOR 0.60, 95% CI 0.28-1.29, P=0.19)

Secondary outcomes similarly showed no significant difference between those taking JAK inhibitors tofacitinib or upadacitinib and those taking TNF inhibitors infliximab or adalimumab. All-cause mortality was 0.99% in the JAK inhibitor group and 1.71% in the TNF inhibitor group (aOR 0.66, 95% CI 0.29-1.48, P=0.31).

Incidence of malignancy was 2.16% in the JAK inhibitor group and 1.26% in the TNF inhibitor group (aOR 0.60, 95% CI 0.30-1.17, P=0.13), and incidence of venous thromboembolism was 1.76% in the JAK inhibitor group and 1.64% in the TNF inhibitor group (aOR 0.82, 95% CI 0.41-1.65, P=0.59).

Subgroup analyses confirmed the lack of significant differences based on individual types of JAK inhibitors. Risk of major adverse cardiovascular events was no different between tofacitinib and the TNF inhibitors (aOR 0.62, 95% CI 0.33-1.14, P=0.12) or between upadacitinib and TNF inhibitors (aOR 1.06, 95% CI 0.53-2.13, P=0.85). There was also no significant difference in major cardiac events between those age 65 and older and those under 65 years old.