No Extra C. Diff Risk Observed With Vedolizumab in Ulcerative Colitis

Risk for Clostridioides difficile (C. diff) infection wasn't any greater with vedolizumab (Entyvio) versus anti-tumor necrosis factor (TNF) agents for ulcerative colitis, a researcher reported.

In a study of over 800 patients with biologic-naive ulcerative colitis, starting treatment with the α4β7 integrin receptor antagonist vedolizumab didn't hold a significantly higher risk for developing C. diff compared with infliximab (Remicade) or adalimumab (Humira) in an adjusted model (HR 0.33, 95% CI 0.05-2.03), reported Rahul S. Dalal, MD, of Harvard Medical School in Boston.

On univariable analysis, patients on vedolizumab actually saw numerically lower rates of C. diff infection (1% vs 7%), C. diff-related hospitalizations (1% vs 4%), and colectomy (0% vs 2%) versus those on anti-TNF agents, Dalal said at the virtual Advances in Inflammatory Bowel Diseases meeting.

"Vedolizumab targets lymphocyte trafficking to the intestines, which raises theoretical concern regarding gastrointestinal infections with this therapy," he said. "In Crohn's disease, there is data to suggest that patients treated with vedolizumab may be at greater risk of serious gastrointestinal infections compared to patients treated with anti-TNF agents."

But there haven't yet been similar observations in ulcerative colitis, Dalal added, saying that "to our knowledge, no one has investigated C. diff specifically, which is arguably the most consequential gastrointestinal infection for the IBD [inflammatory bowel disease] population."

This specific infection is "particularly troublesome" for patients with ulcerative colitis since it often leads to more refractory colitis and need for surgery, pointed out Russell Cohen, MD, of the University of Chicago Medicine, who was not involved with the study.

Although he felt these results were encouraging, Cohen told MedPage Today that more studies are needed before taking this as fact.

Dalal agreed, stating that future prospective research that directly compares the risk of infectious complications between different classes of biologic therapies for IBD are warranted. But in the meantime, his group suggested these findings should provide some reassurance to ulcerative colitis providers when considering vedolizumab as a first-line biologic.

Echoing this sentiment, Bincy Abraham, MD, of Houston Methodist Hospital, said this study simply "reinforces the safety of vedolizumab."

Abraham, who wasn't involved with the study, commented that while its widely known that ulcerative colitis patients face a higher risk of C. diff, it was uncertain whether the "theoretical risk" of vedolizumab would hold true.

Also commenting on the study, Matilda Hagan, MD, of Mercy Medical Center in Baltimore, pointed out some key baseline differences between the two treatment groups. Specifically, she highlighted that ulcerative colitis patients with more severe disease were more likely to be treated with an anti-TNF agent than vedolizumab -- reflective of current clinical practice -- as demonstrated by significant differences in baseline C-reactive protein levels, hospitalizations, and endoscopic Mayo scores.

"C. diff as a complication is more closely associated with severity of underlying ulcerative colitis," explained Hagan, who wasn't involved with the study, adding that she wasn't surprised by the results.

"I don't anticipate that the findings of this study will change current clinical practice," she stated.

Touching on this, Dalal explained that since the submission of their abstract, his group conducted an additional subgroup analysis for patients meeting criteria for severe C. diff -- defined as a white blood cells over 15,000 or serum creatinine over 1.5 mg/dL -- that found vedolizumab to be associated with a significantly reduced risk when compared to anti-TNF agents.

For the current study, Dalal's group retrospectively evaluated data on 805 biologic-naive patients with ulcerative colitis who initiated vedolizumab (n=195) or anti-TNF agents (n=610) from 2014 to 2020.

The main outcome assessed was time to C. diff infection, defined as a positive PCR or stool toxin. Other outcomes measured also included colectomy risk, C. diff-related hospitalizations, and death within 30 days of diagnosis (there were none in either group).

Overall, 55% of patients were women and the vast majority were white. Those on an anti-TNF agent were on average younger than those on vedolizumab (35 vs 48 years). More patients on an anti-TNF agent were on corticosteroids and more patients on an anti-TNF agent had a hospitalization for ulcerative colitis within the prior 12 months (42% vs 14%).

Along with its retrospective design, the lack of assessment of additional safety outcomes was a study limitation.

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