Introduction:

The FDA recently limited the use of Janus kinase (JAK) inhibitors to patients who have not responded to tumor necrosis factor (TNF) antagonists. This decision was based on findings from a large clinical trial in older adults with rheumatoid arthritis and at least one cardiovascular risk factor, where tofacitinib was associated with a higher risk of adverse events—including major adverse cardiovascular events (MACE)—compared to TNF antagonists. Whether these findings apply across all JAK inhibitors, immune-mediated inflammatory disorders (IMIDs), and age groups remains uncertain.

Objective:

To assess and compare the real-world risk of MACE between JAK inhibitors and TNF antagonists in adults with IMIDs through a systematic review and meta-analysis of observational studies.

Methods:

Observational studies involving adults with IMIDs (including rheumatoid arthritis, IBD, psoriasis/psoriatic arthritis, and spondyloarthropathy) were identified through multiple databases (up to July 27, 2024). Studies were included if they reported MACE outcomes for both JAK inhibitors and TNF antagonists. Incidence rates and hazard ratios were pooled using a random-effects meta-analysis, adjusting for key confounders.

Results:

Overall Incidence Rates:

Comparative Risk:

Conclusion:

In real-world comparative studies, the use of JAK inhibitors was not associated with a higher risk of MACE compared to TNF antagonists in patients with IMIDs.

Digestive Disease Week 2025, May 3rd – 6th, San Diego