Advanced therapy & serious infections in IBD

Advanced therapy & serious infections in IBD

May 2, 2023

Issue 09

Clinical Question

Which biologics and oral small molecules are associated with the highest risk of adverse events in IBD?

Editor’s Bottom Line

Safety is an important criterion for choice among available advanced therapies for inflammatory bowel disease. Although all mechanisms of action are generally well tolerated, there may be advantages to anti-integrin and anti-IL12/23 therapy.


Solitano V, Facciorusso A, Jess T, et al. Comparative Risk of Serious Infections With Biologic Agents and Oral Small Molecules in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2023;21(4):907–21.e2.;


This international, multicenter systematic review included 20 head-to-head studies—2 randomized, controls trials and 18 cohort studies—comparing the risk of serious infections with anti-tumor necrosis factor (TNF) agents, vedolizumab, ustekinumab, tofacitinib, filgotinib, and ozanimod in patients with IBD. Five studies including roughly 23,000 IBD patients compared ustekinumab to anti-TNF agents, 17 cohorts with over 51,000 patients compared vedolizumab to anti-TNF drugs and an overlapping five cohorts compared ustekinumab to vedolizumab in 1,420 patients. The median follow-up was seven months after drug initiation. In 15 of the studies, the median follow-up was at least one year. The studies were published or presented between 2018 and 2022.

The analysis found median rates of serious infections per 100 patients treated were 6.7 with anti-TNF drugs, 4.2 with vedolizumab, 4.3 with ustekinumab and 5.6 with tofacitinib. There were no significant differences in the observed risk of serious infections between vedolizumab and anti-TNF drugs for the overall population of IBD patients [Odds Ratio (OR): 0.84; 95% Confidence Interval (CI), 0.68–1.04). However, a subgroup analysis found vedolizumab recipients with ulcerative colitis had a lower risk of serious infections than those receiving anti-TNF agents (OR: 0.68; 95% CI, 0.56–0.83). Controlling for age, sex, prior biologic exposure and choice of monotherapy or combination therapy did not affect the association.

Ustekinumab was linked with a lower risk of serious infections than both anti-TNF antagonists (OR: 0.49; 95% CI, 0.25–0.93) and vedolizumab (OR: 0.40; 95% CI, 0.17–0.93).

There were insufficient data comparing newer biologics and small molecules to anti-TNF agents, vedolizumab and ustekinumab.


Study Design: Meta-analysis

Funding: The National Institute of Diabetes and Digestive and Kidney Diseases and the Danish National Research Foundation

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 1b