Comparative Outcomes and Safety of Vedolizumab vs Tumor Necrosis Factor Antagonists for Older Adults With Inflammatory Bowel Diseases

Abstract

ImportanceObservational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials.ObjectiveTo compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD.Design, Setting, and ParticipantsThis active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022.InterventionsTreatment with vedolizumab or TNF antagonists.Main Outcomes and MeasuresThe primary effectiveness outcome was 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 were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score–matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors.ResultsThe study compared 377 older patients with IBD with incident use of vedolizumab (202 women [53.6%]; mean [SD] age, 61.2 [8.3] years; 177 [46.9%] with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women [54.6%]; mean [SD] age, 61.3 [8.1] years; 182 [48.3%] with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69), including higher risk of 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). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.Conclusions and RelevanceIn 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.

Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review

“…Additionally, the followup period was too short to assess cancer outcomes, similar to other recent studies [173]. Another comparative effectiveness study involving 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register, consisting of 377 patients using VDZ and 377 using ustekinumab (UST), reported very few cases of new malignant neoplasms (<5 events), making it impossible to compare the safety outcomes between the two drugs [174].…”

Cardiovascular implications of inflammatory bowel disease: An updated review

“…The anti-TNF-α agents may be associated with reduced risk of new-onset acute arterial events and prevent recurrence when used in patients with previous history of acute arterial events. Vedolizumab and ustekinumab have not reported any augmented risk of ASCVD[ 134 , 135 ].…”

Efficacy and Safety of Biological Therapies and JAK Inhibitors in Older Patients with Inflammatory Bowel Disease

“…In a propensity score-matched comparison study with VEDO, IFX showed a lower probability of treatment failures in older patients with comparable CCI and treatment-line in both groups [ 35 ].…”

“…In comparison with other biological treatments, e.g., VEDO, IFX showed no major risk of infections in older patients with fewer comorbidities [ 35 ] (p. 6) but a significantly higher risk of infection-related hospitalizations in older patients with more severe comorbidities [ 51 ]. Similar data were reported when comparing anti-TNFs with VEDO or USTE, showing no overall difference in older patients but more infection-related hospitalizations in the anti-TNF-treated patients, with a CCI of >1 [ 52 ].…”

“…In this study, a CCI of >2 in CD patients was positively associated with lower persistence. In a large study comparing VEDO with anti-TNFs in a mixed, partially anti-TNF-experienced population, VEDO showed a higher risk of failure in CD but not in UC [ 35 ] (p. 6).…”