Higher Risk of Treatment Failure With Vedolizumab Compared to TNF Antagonists for Older IBD Patients

Siddharth Singh, MD, MS

A new comparative analysis shows older patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) antagonists are less likely to suffer from treatment failure compared to similar patients treated with vedolizumab.

A team, led by Siddharth Singh, MD, MS, Division of Gastroenterology, Department of Medicine, University of California, San Diego, compared the effectiveness and safety of vedolizumab compared to TNF for older patients with IBD.

“Observational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials,” the authors wrote.

Comparing Vedolizumab and TNF Antagonists

In the active comparator, new-user design, comparative effectiveness study, the investigators examined 754 older patients with IBD from the Danish National Patient Register between 2005-2018. Each patient was aged at least 50 years.

There was a mean follow-up after treatment initiation of 32-40 weeks.

The final analysis included 377 older patients with IBD with incident use of vedolizumab and 377 patients with incident use of TNF antagonists. The mean age of the vedolizumab group was 61.2 years and the mean age of the TNF group was 61.3 years.

The investigators sought primary effectiveness outcome of treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy.

Secondary effectiveness outcomes also included time to each individual component of the composite effectiveness outcome.

The investigators also sought primary safety outcomes of the risk of serious infections, defined as infections requiring hospitalization.

Finally, they conducted an even propensity score-matched analysis accounting for patient-, disease-, and treatment-associated factors.

TNF Antagonists Clearly Better

The results show vedolizumab was linked to an increased risk of treatment failure compared to TNF antagonists (1-year risk, 45.4% vs 34.7%; aHR, 1.31; 95% CI, 1.02-1.69). This included a higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; aHR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; aHR, 2.39; 95% CI, 1.45-3.94).

The investigators also conducted a subgroup analysis by IBD phenotype and found patients with Crohn’s disease treated with vedolizumab had a 77% higher risk of treatment failure (aHR, 1.77; 95% CI, 1.21-2.58). However, there were no difference in risk of treatment failure found in patients with ulcerative colitis (aHR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction).

There was also no significant differences in the risk of serious infections, both overall (1-year risk, 8.2% vs 8.7%; aHR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.

“In this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage,” the authors wrote.

The study, “Comparative Outcomes and Safety of Vedolizumab vs Tumor Necrosis Factor Antagonists for Older Adults With Inflammatory Bowel Diseases,” was published online in JAMA Network Open.