Intensive care medicine

Ustekinumab

Inflammatory bowel disease

Tofacitinib

Adalimumab

Rheumatoid arthritis

Political science

Crohn's disease

Meta-analysis

Internal medicine

Odds ratio

MEDLINE

Medicine

Inflammatory Bowel Diseases

Ulcerative colitis

Gastroenterology

Vedolizumab

Disease

Clinical Gastroenterology and Hepatology

Background & AimsSafety 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.MethodsThrough a systematic search until February 28, 2022, we included 20 head-to-head studies comparing risk of serious infections with tumor necrosis factor α (TNFα) antagonists, vedolizumab, ustekinumab, tofacitinib, filgotinib, and ozanimod in patients with IBD. We performed random-effects meta-analysis comparing different advanced therapies.ResultsNo significant difference was observed in the risk of serious infections between vedolizumab vs TNFα 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 TNFα 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.ConclusionsVedolizumab may offer net benefit over TNFα antagonists in patients with ulcerative colitis, but not in CD. Ustekinumab may offer net benefit over TNFα antagonists and vedolizumab in patients with CD. 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. Through a systematic search until February 28, 2022, we included 20 head-to-head studies comparing risk of serious infections with tumor necrosis factor α (TNFα) antagonists, vedolizumab, ustekinumab, tofacitinib, filgotinib, and ozanimod in patients with IBD. We performed random-effects meta-analysis comparing different advanced therapies. No significant difference was observed in the risk of serious infections between vedolizumab vs TNFα 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 TNFα 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. Vedolizumab may offer net benefit over TNFα antagonists in patients with ulcerative colitis, but not in CD. Ustekinumab may offer net benefit over TNFα antagonists and vedolizumab in patients with CD.

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