番茄社区

Treatment with vedolizumab (Entyvio) was associated with a higher risk of treatment failure compared with tumor necrosis factor (TNF) inhibitors in older adults with inflammatory bowel disease (IBD), especially those with Crohn's disease, according to an observational comparative effectiveness study.

In a propensity score-matched analysis including 754 patients ages 50 and up, use of vedolizumab was associated with a 45.4% risk of treatment failure -- defined as a composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after biologic therapy initiation -- at 1 year compared with a 34.7% risk with use of TNF inhibitors (adjusted HR 1.31, 95% CI 1.02-1.69), reported Siddharth Singh, MD, MS, of the University of California San Diego, and colleagues.

Specifically, the 1-year risk of IBD-related hospitalization was 27.8% with vedolizumab versus 16.3% with TNF inhibitors (aHR 1.48, 95% CI 1.03-2.15) and the 1-year risk of IBD-related major abdominal surgery was 21.3% versus 8.0%, respectively (aHR 2.39, 95% CI 1.45-3.94), they noted in .

"These findings will inform optimal choice of different biologic agents depending on a patient's risk of disease- and treatment-associated complications," Singh and team concluded.

There was no statistically significant difference in the need for corticosteroids with vedolizumab compared with TNF inhibitors at 1 year (28.4% vs 24.0%; aHR 1.24, 95% CI 0.91-1.68).

In a subgroup analysis by IBD phenotype, vedolizumab was associated with a 77% higher risk of treatment failure among those with Crohn's disease (aHR 1.77, 95% CI 1.21-2.58), while no difference in risk was seen in those with ulcerative colitis (aHR 1.04, 95% CI 0.75-1.43).

Additionally, vedolizumab was associated with a greater need for corticosteroids versus TNF inhibitors among patients with Crohn's disease (aHR 2.14, 95% CI 1.29-3.55), but not ulcerative colitis (aHR 0.83, 95% CI 0.56-1.24).

"In the absence of predictive biomarkers, these findings suggest that older patients with CD [Crohn's disease], particularly those at higher risk of disease-associated complications, may be preferentially treated with TNF antagonists rather than vedolizumab," the authors noted.

Reached for comment, Dana Lukin, MD, PhD, of Weill Cornell Medicine in New York City, told 番茄社区, "These results are similar to other all-ages cohorts, and reiterate the favorable safety and efficacy of vedolizumab for ulcerative colitis, but the lack of a clear benefit in Crohn's disease."

Of note, there was no significant difference between vedolizumab and TNF inhibitors groups in the risk of serious infections at 1 year overall (8.2% vs 8.7%, respectively; aHR 1.04, 95% CI 0.58-1.85) and by IBD phenotype.

IBD-related healthcare costs among older patients are rising, and older adults have been largely excluded from clinical trials even after previous studies found to younger patients, Singh's group noted. Older IBD patients are often "undertreated and mismanaged" with long-term corticosteroids, and steroid-sparing therapies are not commonly used because of safety concerns. While TNF inhibitors are the mainstay for IBD patients refractory to conventional therapies, vedolizumab is a newer option that selectively targets the gut, thereby providing a safety advantage.

For this study, Singh and colleagues examined data from the Danish National Patient Register on 754 IBD patients from January 2005 through December 2018. Mean follow-up after treatment initiation was 32 to 40 weeks.

They compared 377 patients with incident use of vedolizumab with 377 patients with incident use of TNF inhibitors, including infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi). Mean age in both groups was 61, 54-55% were women, and 47-48% had Crohn's disease.

Over twice as many TNF inhibitors patients were naive to biologic agents compared with vedolizumab patients (26% vs 10%). Notably, 42-46% were on corticosteroids for at least 6 months before initiating biologics.

No significant differences were seen between groups based on sex, age at biologic therapy initiation, biologic monotherapy/combination therapy with immunomodulators, or in the overall risk of major adverse cardiac events and venous thromboembolic events.

Singh and colleagues noted that they did not have access to subjective or objective measures of disease activity or endoscopy reports, which was a study limitation. In addition, due to the study's observational nature, they could not rule out unobserved confounders, especially those owing to treatment selection.

Comment