Gastrointestinal Perforation as a Safety Concern Among Patients With Rheumatoid Arthritis Receiving JAK Inhibitor Therapy: A Systematic Review and Network Meta-Analysis.

Abstract

Gastrointestinal perforation (GIP) is a rare and life-threatening safety concern associated with JAK inhibitors (JAKi). We aimed to review the evidence regarding the risk of GIP associated with the use of JAKi in patients with rheumatoid arthritis (RA) using a systematic review and network meta-analysis approach. A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through August 2024. Included were randomized controlled trials (RCTs) comparing JAKi with other comparators in adult patients with RA (age ≥18 years) and reports of GIP. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Surface under the cumulative ranking curves (SUCRA) were used to rank interventions. A total of 23 RCTs involving 20,023 patients were included, with a median follow-up time of 24 weeks. The overall incidence of GIP among JAKi-treated patients was 0.19% (95% CI 0.10-0.35%), with 24 events occurring out of 12,430 patients. Pairwise meta-analysis showed that the risk of GIP among patients taking JAKi was not significantly increased compared to that in those taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (RR 1.02; 95% CI 0.41-2.56; I² = 0.0%). The results of the network meta-analysis are consistent with the pairwise meta-analysis findings. Compared to csDMARDs, there was no statistically significant increase in GIP risk with JAKi (RR 0.83; 95% CI 0.37-1.84; P = 0.64) without inconsistency (P = 0.55). The SUCRA of JAKi (50.8%) and biologic DMARDs (77.0%) indicated a low risk of GIP. JAKi were not associated with an increased risk of GIP compared to csDMARDs in patients with RA.