Comparative Risk of Serious Infections With Biologic Agents and Oral Small Molecules in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

BACKGROUND & AIMS: Safety is a key consideration when choosing advanced therapies (biologic agents and oral small -molecule inhibitors/modulators) in patients with inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis comparing the risk of serious infections with advanced therapies in active comparator studies. METHODS: Through a systematic search until February 28, 2022, we included 20 head-to-head studies comparing risk of serious infections with tumor necrosis factor a (TNFa) antagonists, vedoli-zumab, ustekinumab, tofacitinib, filgotinib, and ozanimod in patients with IBD. We performed random-effects meta-analysis comparing different advanced therapies. RESULTS: No significant difference was observed in the risk of serious infections between vedolizumab vs TNFa antagonists in all patients with IBD (17 cohorts: odds ratio [OR], 0.84; 95% CI, 0.68-1.04), with moderate heterogeneity (I2 = 37%); on subgroup analysis, vedolizumab was associated with a lower risk of serious infections in patients with ulcerative colitis (11 cohorts: OR, 0.68; 95% CI, 0.56-0.83; I2 = 0%), but not in Crohn's disease (CD) (9 cohorts: OR, 1.03; 95% CI, 0.78- 1.35; I2 = 42%). Age, sex, prior biologic exposure, and use of biologic monotherapy did not influence this association. In patients with CD, ustekinumab was associated with a lower risk of serious infections vs TNFa antagonists (3 cohorts: OR, 0.49; 95% CI, 0.25-0.93; I2 = 16%) and vs vedolizumab (3 cohorts: OR, 0.40; 95% CI, 0.17-0.93; I2 = 67%). Few studies compared other advanced therapies. CONCLUSIONS: Vedolizumab may offer net benefit over TNFa antagonists in patients with ulcerative colitis, but not in CD. Ustekinumab may offer net benefit over TNFa antagonists and vedolizumab in pa-tients with CD.