Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.
Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.
In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.
These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.
In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.
The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).
Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.
Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.
In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.
“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
