Findings indicate that vedolizumab is associated with an increased risk for treatment failure in older patients with inflammatory bowel disease (IBD), as compared with tumor necrosis factor (TNF) antagonists, according to a new study published in JAMA Network Open.
Dr. Siddharth Singh
Although the incidence and prevalence of IBD among older adults are rapidly increasing, there is a lack of evidence-based treatment guidance for these patients, who represent less than 5% of participants in IBD-related clinical trials, wrote Siddharth Singh, MD, a gastroenterologist and assistant professor of medicine at the University of California, San Diego, and colleagues.
“Older patients are frequently undertreated and mismanaged with long-term corticosteroid use and limited use of steroid-sparing therapies owing to patients’ and clinicians’ concerns about the safety of immunosuppressive therapy,” the authors wrote. “There is considerable need for evidence-based treatment guidance for older patients with IBD.”
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The researchers undertook an observational study of the comparative effectiveness of vedolizumab versus TNF antagonists (namely infliximab, adalimumab, and golimumab) among older patients with IBD in Denmark. Using the Danish National Patient Register, the authors included 754 patients aged 50 years and older who received treatment between 2005 and 2018.
The primary effectiveness outcome was treatment failure, defined as the composite 1-year risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with a biologic. Secondary effectiveness outcomes included time to each component included in the composite score.
The primary safety outcome was the risk of serious infections, defined as those that required hospitalization. Secondary safety outcomes were risk of cancer and major adverse cardiovascular or venous thromboembolic events.
The researchers conducted a 1:1 propensity score-matched analysis, accounting for patient, disease, and treatment factors. The 754 patients included 377 incident users of vedolizumab, including 177 with Crohn’s disease; and 377 incident users of TNF antagonists, including 182 with Crohn’s disease. The average follow-up after treatment initiation occurred between 32 and 40 weeks.
Notably, patients treated with vedolizumab were more likely than those treated with TNF antagonists to have multimorbidity, at 16.2% versus 14.1%, and a higher burden of frailty, at 2.7% versus 1.9%. No significant differences were observed in the proportion of patients with recent immunomodulator and corticosteroid exposure.
Overall, vedolizumab was associated with a 31% increased risk of treatment failure (45.4%), compared with TNF antagonists (34.7%). This included an increased risk of IBD-related hospitalization (27.8% versus 16.3%) and IBD-related major abdominal surgery (21.3% versus 8%).
Among patients with Crohn’s disease, vedolizumab was associated with a 77% increased risk of treatment failure, as well as a greater need for corticosteroids. There was no significant difference in the risk of treatment failure or need for corticosteroids in patients with ulcerative colitis
No significant differences were seen in the risk of serious infections between patients treated with vedolizumab or TNF antagonists, at 8.2% versus 8.7%. This didn’t change by IBD phenotype, age at time of biologic therapy initiation, or treatment with biologic monotherapy versus combination therapy with immunomodulators.
The overall incidence of major adverse cardiovascular or venous thromboembolic events was similar among the groups. Rates of new malignant neoplasms were low, with fewer than five events.
In a subgroup analysis based on the Charlson Comorbidity Index, vedolizumab was associated with a 63% increased risk of treatment failure for patients without comorbidities but not for patients with comorbidities.
“This study adds to the body of literature comparing vedolizumab and anti-TNF in older adults. The findings have been mixed, in some part due to differences in study designs,” said Ashwin N. Ananthakrishnan, MBBS, MPH, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston.
Dr. Ashwin N. Ananthakrishnan
Dr. Ananthakrishnan, who wasn’t involved with this study, has previously researched the two treatments and found that they are comparably safe in older adults. In fact, among patients with significant comorbidity, vedolizumab may be safer. However, the Danish study wasn’t powered to describe that, he said. Moreover, patient characteristics and treatment approaches likely differ between the United States and Denmark.
“Overall, the findings are reassuring. Often when we treat older adults, the emphasis is on safety,” he said. “But by highlighting the difference in clinical response rates – their findings being consistent with a study we published a few years ago – it highlights the importance of also considering efficacy and onset of action for specific disease phenotypes in treatment selection.”
Dr. Ananthakrishnan and colleagues are currently developing clinical tools for risk stratification and prognostication in older adults with IBD, including functional and frailty assessments. “Biologically, older adults may be particularly vulnerable to specific treatment risks such as infections and cancer, but they are also vulnerable to the consequences of untreated disease, including loss of functional independence and frailty,” he explained. “Thus, arriving at the right risk to benefit balance is critically important when making treatment decisions for older adults.”
The study by Dr. Singh and colleagues was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Danish National Research Foundation. Dr. Singh reported receiving grants from pharmaceutical companies unrelated to the study, as well as support from the International Organization for the Study of Inflammatory Bowel Disease Operating Grant and Litwin Pioneers in IBD. No other disclosures were reported. Dr. Ananthakrishnan reported no relevant disclosures.