Among older patients with inflammatory bowel disease (IBD), vedolizumab was associated with an increased risk for treatment failure compared with tumor necrosis factor (TNF) antagonists, especially in patients with Crohn disease (CD), with no differences in the risk for serious infections, according to study findings published in JAMA Network Open.
The propensity score-matched cohort study compared the efficacy and safety of vedolizumab vs TNF antagonists in patients with IBD. Participants from the Danish National Patient Registry were aged at least 50 years and living in Denmark between January 1, 2005, and December 31, 2018.
The primary exposure was treatment with vedolizumab, and the primary comparator was treatment with TNF antagonists. The primary effectiveness outcome was treatment failure, which was a composite of time to IBD-related hospitalization, IBD-related major abdominal surgery, or new corticosteroid prescription greater than 6 weeks after biologic therapy initiation. The primary safety outcome was risk for serious infections requiring hospitalization. Statistical analysis was conducted from February 1 to April 27, 2022.
Researchers compared 377 incident users of vedolizumab (women, 53.6%; mean [SD] age, 61.2[8.3] years; 177[46.9%] with CD) with 377 incident users of specific TNF antagonists (women, 54.6%; mean [SD] age, 61.3[8.1] years; 182[48.3%] with CD) after 1:1 propensity score matching. The mean (SD) follow-up ranged from 33 (30) to 40 (31) weeks in patients treated with vedolizumab and from 32 (30) to 39 (32) weeks in those treated with TNF antagonists.
Vedolizumab was associated with an overall 31% higher risk for treatment failure vs TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69). In subgroup analysis based on IBD phenotype, vedolizumab was associated with a 77% increased risk for treatment failure vs TNF antagonists in patients with CD (adjusted HR, 1.77; 95% CI, 1.21-2.58). No significant differences in the risk for treatment failure were observed in patients with ulcerative colitis (UC) (adjusted HR, 1.04; 95% CI, 0.75-1.43; P =.03 for interaction).
Vedolizumab was associated with an increased risk for IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94) compared with TNF antagonists.
No significant differences were found for the risk for serious infections between patients treated with vedolizumab and those who received TNF antagonists (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85). The overall incidence of major adverse cardiovascular events (MACE) and venous thromboembolic events was comparable in patients with IBD treated with vedolizumab vs TNF antagonists (1-year risk of 4.0% vs 2.8%; adjusted HR, 0.90; 95% CI, 0.41-2.01).
Study limitations include no access to subjective or objective measures of disease activity or endoscopy reports or accurate details of disease location or extent, behavior, and whether treatment was escalated or optimized based on drug concentration. In addition, unobserved confounders cannot be ruled out, especially those owing to treatment selection. Further, older patients were defined as those older than 50 years, and other safety outcomes such as risk of MACE, venous thromboembolic events, and cancer could not be compared.
“In the absence of predictive biomarkers, these findings suggest that older patients with CD, particularly those at higher risk of disease-associated complications, may be preferentially treated with TNF antagonists rather than vedolizumab,” the study authors wrote. “Future prospective registry and observational studies are warranted to confirm these findings and evaluate the comparative effectiveness and safety of other non-TNF antagonist biologic therapies such as ustekinumab and Janus kinase inhibitors.”
Disclosure: One of study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Singh S, Iversen AT, Allin KH, Jess T. Comparative outcomes and safety of vedolizumab vs tumor necrosis factor antagonists for older adults with inflammatory bowel diseases. JAMA Netw Open. 2022;5(9):e2234200. doi:10.1001/jamanetworkopen.2022.34200