Clin Gastroenterol Hepatol. 2023 Apr;21(4):907-921.e2.doi: 10.1016/j.cgh.2022.07.032. Epub 2022 Aug 6.

Virginia Solitano ¹, Antonio Facciorusso ², Tine Jess ³, Christopher Ma ⁴, Cesare Hassan ⁵, Alessandro Repici ⁵, Vipul Jairath ⁶, Alessandro Armuzzi ⁵, Siddharth Singh ⁷

Author information

¹Department of Biomedical Sciences, Humanitas University, Milan, Italy.

²Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy.

³Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

⁴Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Chief Medical Officer, Global Medical Research and Development, Alimentiv, Inc, London, Ontario, Canada.

⁵Department of Biomedical Sciences, Humanitas University, Milan, Italy; Department of Gastroenterology, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Milan, Italy.

⁶Chief Medical Officer, Global Medical Research and Development, Alimentiv, Inc, London, Ontario, Canada; Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.

⁷Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.

Abstract

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 α (TNFα) antagonists, vedolizumab, 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 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.

Conclusions: 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.