JAK Inhibitors Not Linked to Increased Gastrointestinal Perforation Risk in Patients With RA
A new systematic review and network meta-analysis published in Arthritis Care & Research, offers important reassurance regarding the gastrointestinal safety of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA). The analysis found no significant increase in the risk of gastrointestinal perforation (GIP) compared to conventional synthetic DMARDs (csDMARDs).
The review included 23 randomized controlled trials involving 20,023 RA patients, with a median follow-up of 24 weeks. Among JAKi-treated patients, the overall incidence of GIP was low, at 0.19% (95% CI: 0.10–0.35%), based on 24 events among 12,430 patients. "Pairwise meta-analysis showed that the risk of GIP among JAKi was not significantly increased compared to csDMARDs (RR = 1.02; 95% CI: 0.41–2.56; I² = 0.0%)," the authors reported.
Network meta-analysis results confirmed the pairwise findings. Compared to csDMARDs, JAKi use was not associated with a statistically significant increase in GIP risk (RR = 0.83; 95% CI: 0.37–1.84; p=0.64). Furthermore, the Surface Under the Cumulative Ranking (SUCRA) values indicated a low risk of GIP for both JAKi (50.8%) and bDMARDs (77.0%).
"JAK inhibitors were not associated with an increased risk of gastrointestinal perforation compared to csDMARDs in RA patients," the study concluded.
For practicing rheumatologists, these findings provide important guidance when considering JAK inhibitors, particularly in patients concerned about gastrointestinal adverse events. Careful patient selection and monitoring remain essential, but the overall GIP risk profile appears comparable to traditional therapies.
Reference
Sathapanasiri T, Meraz M, Mokri H, et al. Gastrointestinal perforation as a safety concern among patients with rheumatoid arthritis on Janus kinase inhibitor therapy: A systematic review and network meta-analysis. Arthritis Care Res (Hoboken). Published online April 20, 2025. doi:10.1002/acr.25554
