June 06, 2026
A Mayo Clinic study of patients with inflammatory bowel disease (IBD) has found that Janus kinase (JAK) inhibitors aren't associated with an increased risk of serious complications compared with tumor necrosis factor-alpha (TNF-a) antagonists. Unlike some previous research comparing JAK and TNF-a antagonists, the Mayo Clinic study focused exclusively on people with IBD.
JAK inhibitors have emerged as an important treatment option for IBD, offering rapid and targeted immunomodulation. However, in 2019, the Food and Drug Administration (FDA) modified the labeling of JAK inhibitors based on the results of the ORAL Surveillance trial. That noninferiority trial compared the JAK inhibitor tofacitinib and TNF-a antagonists in patients with rheumatoid arthritis who were age 50 and older and had at least one additional cardiovascular risk factor.
ORAL Surveillance found that the JAK inhibitor was associated with a higher risk of serious infections, venous thromboembolism (VTE) and major adverse cardiac events (MACE). It's unclear whether those findings apply to patients with IBD, who are generally younger and have a lower burden of cardiovascular risk factors.
Mayo Clinic gastroenterologists conducted a large-scale, retrospective, observational study of people with IBD who were new users of JAK inhibitors or TNF-a antagonists between 2016 and 2023. The cohort, drawn from an administrative claims database, included 856 patients treated with JAK inhibitors and 9,422 patients treated with TNF-a antagonists. Study results were published in Clinical Gastroenterology and Hepatology.
Key findings:
- JAK inhibitors were associated with higher risk of overall infections but not serious infections requiring hospitalization.
- There was no difference between the two groups in the risk of VTE. On further analysis using a more specific definition of VTE — restricted to events requiring hospitalization or emergency department visits — JAK inhibitors were associated with a lower incidence and risk of VTE compared with TNF-a antagonists.
- There was no difference between the two groups in the overall incidence and risk of MACE. The overall incidence and risk of MACE was low with JAK inhibitors — including in patients like those in the ORAL Surveillance trial deemed at high risk of MACE — and might be lower compared with TNF-a antagonists.
- The results were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitor, age, prior biologic exposure, concomitant use of corticosteroids and baseline risk of adverse events.
"These findings are reassuring, as they don't identify a significantly increased hazard of JAK inhibitors for patients with IBD," says Sid Singh, M.B.B.S., a gastroenterologist in the Inflammatory Bowel Disease Clinic at Mayo Clinic in Phoenix/Scottsdale, Arizona. "There have been very few real-world studies on the comparative safety of JAK inhibitors versus TNF antagonists in patients with IBD. Our observational study provides novel, robust evidence in favor of the safety of JAK inhibitors in patients with IBD. It's critical for these patients to have an effective medication without the fear of risk of side effects."
The FDA recently updated JAK inhibitor labeling to allow earlier use of those medications for patients with IBD when TNF-a antagonists aren't advisable.
"There is an increasing recognition that patients with IBD may be different," Dr. Singh says. "There is always a balance between a therapy's effectiveness and safety. The risk-benefit balance of JAK inhibitors might be significantly in favor of benefit for IBD patients."
The Mayo Clinic researchers note that JAK inhibitors are highly effective for managing IBD, especially for patients with ulcerative colitis (UC). The JAK inhibitor upadacitinib has been ranked as having the highest efficacy for induction of remission compared with other agents for the treatment of moderate to severe UC.
A relatively small number of patients in the Mayo Clinic study cohort were treated with upadacitinib. Most of the patients in the JAK inhibitor group received tofacitinib.
The Mayo Clinic researchers are updating their study cohort to investigate JAK inhibitor options in more detail. "We're trying to inform the positioning of these medications in terms of real-world effectiveness and safety," Dr. Singh says. "It's not always easy to choose the best medication. At Mayo Clinic, we are trying to provide that evidence, so patients and healthcare professionals are able to make an informed decision."
For more information
Ytterberg SR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. The New England Journal of Medicine. 2022;386:316.
Ahuja D, et al. Comparative safety of Janus kinase inhibitors versus tumor necrosis factor antagonists in patients with inflammatory bowel diseases. Clinical Gastroenterology and Hepatology. 2026;24:794.
Inflammatory Bowel Disease Clinic. Mayo Clinic.
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