Adverse Events in Patients with Inflammatory Bowel Disease Treated with Advanced Therapies: A Nationwide,...

Background: Safety profiles of advanced therapies (ATs) for inflammatory bowel disease (IBD) may be underestimated in clinical trials due to low event rates and heterogeneous adverse events (AEs). Methods: Using Korean nationwide claims data (2012-2022), incident IBD patients were identified and classified into AT and non-AT groups. After:1 propensity score matching, risks of tuberculosis (TB), herpes zoster (HZ), and bowel malignancy as primary AEs, and anxiety/depression as secondary AEs, were evaluated. Results: After matching, 11,205 patients were included in each group. Overall AT use was not associated with a significant increase in TB risk compared with non-AT therapy (hazard ratio [HR] 1.2; p = 0.335), whereas anti-TNF biologics showed higher TB risk (HR 2.0; incidence rate [IR] 100.2 vs. 65.4 per 10⁵ person year [PY]; p < 0.001). AT use was associated with a modestly increased risk of HZ (HR 1.4; IR 2165.8 vs. 2151.3 per 10⁵ PY; p < 0.001), with the highest incidence in small-molecule agents (HR 2.0; IR 4134.2 per 10⁵ PY). The risk of bowel malignancy did not differ between AT and non-AT groups (HR 1.2; p = 0.475). Both anti-TNF and non-anti-TNF biologics were associated with reduced risk of anxiety/depression compared with non-AT therapy (both HR 0.8; p < 0.001 and p = 0.004, respectively). Conclusions: Overall AT use was not associated with an increased risk of TB, whereas anti-TNF biologics were associated with a higher risk of TB. AT use was also associated with an increased risk of HZ, particularly with small-molecule agents, and a lower risk of anxiety/depression.