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Gastrointestinal Perforations Associated With JAK Inhibitors: A Disproportionality Analysis of the FDA Adverse Event
Adam Goldman1,2,3, Emanuel Raschi4, Amit Druyan1,5
1Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel.
United European Gastroenterology Journal
|December 30, 2024
Summary
Rheumatoid arthritis patients on Janus kinase (JAK) inhibitors show increased gastrointestinal perforations compared to those on biologic drugs. Concurrent steroid or NSAID use further elevates this risk, necessitating careful monitoring.
Area of Science:
- Pharmacovigilance and drug safety research.
- Rheumatology and immunology.
- Gastroenterology and adverse event analysis.
Background:
- Rheumatoid arthritis (RA) patients treated with Janus kinase (JAK) inhibitors have shown rare gastrointestinal perforations in clinical trials.
- Large-scale postmarketing data is crucial for investigating this serious adverse event in RA patients on JAK inhibitors.
Purpose of the Study:
- To assess the association between JAK inhibitors and gastrointestinal perforations in RA patients.
- To compare the risk of gastrointestinal perforations with JAK inhibitors versus biological disease-modifying antirheumatic drugs (bDMARDs).
Main Methods:
- Retrospective pharmacovigilance study using FDA adverse event reporting system (July 2014-September 2023).
- Compared gastrointestinal perforation reporting rates between JAK inhibitors and bDMARDs in RA patients.
- Calculated adjusted reporting odds ratio (adj.ROR) using multivariable logistic regression.
Main Results:
- JAK inhibitors were associated with a higher reporting of gastrointestinal perforations (adj.ROR = 1.98) compared to bDMARDs in RA patients.
- Concurrent use of steroids or NSAIDs significantly increased perforation reporting risk (adj.ROR = 2.82).
- All JAK inhibitors (tofacitinib, upadacitinib, baricitinib) showed significant safety signals for gastrointestinal perforations.
Conclusions:
- All JAK inhibitors are linked to increased gastrointestinal perforation reporting in RA patients compared to bDMARDs.
- Clinicians should maintain heightened awareness and surveillance for gastrointestinal perforations in RA patients on JAK inhibitors.
- Further data on inflammatory bowel disease (IBD) patients is needed, but caution is advised.
Keywords:
JAKiadverse eventsanti‐JAKautoimmune diseasesbaricitinibcomplicationspharmacovigilancerheumatoid arthritistofacitinibupadacitinibMore Related Videos
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