Risk of Gastrointestinal Perforations with JAK Inhibitors

Is there a risk of gastrointestinal perforations with JAK inhibitors?

There is a widely held view that JAK inhibitors may increase the risk of gastrointesintal perforations. This appears to be a consideration amongst all JAK inhibitors although tofacitinib has received considerable attention. The mechanisms are not entirely clear although inhibitor of signalling through IL-6 may be an important mechanism.

Authors recently set out to compare the risk of gastrointestinal perforation in patients receiving JAK inhibitors. Rates of GI perforation in patients receiving tofacitinib, baricitinib, upadacitinib, or filgotinib were compared to those receiving the TNF inhibitor adalimumab. The study was conducted in rheumatology patients.

The study included 39,758 patients. 12,335 patients received a JAK inhibitor, and 27,423 patients received the TNF inhibitor adalimumab. The JAK inhibitor group was older and more likely to be female and more likely to be diagnosed with rheumatoid arthritis than the TNF inhibitor group (mean age 58.2 vs 47.3 years; female 76% vs 58%; rheumatoid arthritis 85.3% vs 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% vs 72.7%),

Results

The incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) with JAK inhibitors and and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively.

All in all, the rates of gastrointestinal perforation did not differ between the groups that received a JAK inhibitor vs the TNF inhibitor adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65).

Conclusion

This study suggested that the rates of gastrointestinal perforation did not differ between groups of patients who received JAKi and adalimumab treatment.

To me this is an interesting study but just another study to add to the pile so that someday we can figure out once and for all the true risk of JAK inhibitors.

This study sure is interesting but we always need to be careful with cohort studies. Let’s face it - nothing beats a randomized controlled trial

I’m always careful about using JAK inhibitors in patients with bowel issues. In fact, patients with a history of diverticulitis are never candidates for JAK inhibitors, in my mind. In a study by Curtis et al., seventy percent of patients with perforation in a rheumatology patient model used glucocorticoids, had antecedent diverticulitis, or both.

I think we can all probably agree that GI perforations are super uncommon with JAK inhibitors. However, I don’t think we’re done studying this

REFERENCE

Hoisnard L et al. Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study. Arthritis Rheumatol. 2024 May 3.

Curtis JR et al. The Incidence of Gastrointestinal Perforations Among Rheumatoid Arthritis Patients. Arthritis Rheum. 2011 Feb; 63(2): 346–351.