Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, US researchers have found.
The researchers examined US health insurance claims for three cohorts — patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab — and found no overall difference in infection rates or infection-related hospitalizations between the groups.
But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.
In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”
“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.
The research was published online in The American Journal of Gastroenterology.
Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital in Boston, told Medscape Medical News that the real question, when we’re seeing an older patient, is which medications are safer?
“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”
With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Kochar said the hope is that their study will help doctors feel more confident in prescribing [and] encourage thinking about the patient in a broader manner beyond chronological age.
Real-World Study on Older Adults With IBD
The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.
They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.
Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.
Recognizing the need for real-world studies focused on older adults, Kochar and her colleagues gathered claims data from a commercial US health insurance plan totaling nearly 86 million individuals between 2008 and 2019.
They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.
The cohorts included 2369 patients treated with anti-TNF agents, 972 who were started on vedolizumab, and 352 given ustekinumab.
Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.
The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.
The overall incidence rates for any infection were similar across the three treatment groups, at 3606 per 1000 person-years in the anti-TNF group, 3748 per 1000 person-years in patients given vedolizumab, and 3139 per 1000 person-years in those treated with ustekinumab.
There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab vs anti-TNF agents of 0.94, and for ustekinumab, again vs anti-TNF agents, of 0.92.
However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.
Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of > 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations vs anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.
In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.
Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection vs those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
Results Will Help Refine Clinical Practice
Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York City, said the study is limited by the lack of granular data on disease activity.
Moreover, he told Medscape Medical News that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.
“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Lukin said, and added that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”
He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”
Most importantly, Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.
Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”
“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”
The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.
Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.
American Journal of Gastroenterology. Published online July 20, 2022. Abstract.