BACKGROUND

Clostridioides difficile infection (CDI) is associated with adverse outcomes in ulcerative colitis (UC). There is concern that vedolizumab, which inhibits lymphocyte trafficking to the intestines, may increase the risk of gastrointestinal infections such as CDI when compared to other biologics. We conducted a retrospective cohort study to determine if vedolizumab is associated with an increased risk of CDI compared to anti-TNFa agents in UC.

METHODS

Retrospective cohort study of adult patients with UC initiating infliximab, adalimumab, or vedolizumab 6/1/14-12/31/20 at a large academic health system. Electronic records were manually reviewed. Patients with Crohn's disease, indeterminate colitis, prior biologic exposures, prior colectomy, and non-UC indications for biologics were excluded. Patients were followed until CDI, colectomy, biologic discontinuation/switch, or last gastroenterology encounter through 8/1/21. The primary outcome was time from biologic initiation to first CDI, defined as positive stool C. difficile toxin or toxigenic C. difficile polymerase chain reaction (PCR) with associated CDI antibiotic prescriptions. Secondary outcomes included CDI-related hospitalization, colectomy, or death within 30 days of CDI. The primary exposure was vedolizumab vs anti-TNFa therapy. Other independent variables included demographics and UC history/severity factors. Propensity scores (PSs) were calculated using logistic regression of vedolizumab vs anti-TNFa on the following covariates: age, sex, Caucasian, body mass index (BMI), disease duration, current systemic corticosteroid use, UC-related hospitalization within prior 12 months, last Mayo endoscopic subscore, Montreal disease extent, albumin, and malignancy history. Inverse probability of treatment weighting (IPTW) was performed using PSs. An univariable Cox proportional hazards model was fit to calculate the unadjusted hazard ratio (HR) of CDI for vedolizumab vs anti-TNFa. A multivariable, IPT-weighted Cox model was then fit with two additional covariates extrinsic to the PS: pre-biologic CDI and immunomodulator exposure (time-varying covariate). Patients were censored at loss of follow-up, biologic discontinuation, or colectomy.

RESULTS

805 UC patients initiated vedolizumab (n = 195) or anti-TNFa agents (n = 610). Vedolizumab patients were older and less commonly received systemic corticosteroids or had UC-related hospitalization within 12 months pre-biologic initiation. There were 43 CDIs over 1,436 patient-years follow-up. CDI and CDI hospitalization occurred less commonly with vedolizumab vs anti-TNFa (CDI: 1.0% vs 6.7%, p = 0.001; CDI hospitalization: 1.0% vs 3.8%, p = 0.042 by log-rank test). There were no differences in colectomies or deaths or exposure to antibiotics/corticosteroids during follow-up or within 30 days preceding CDI. The unadjusted Cox model demonstrated a lower hazard of CDI for vedolizumab vs anti-TNFa (HR 0.17, 95% CI 0.04-0.71). The multivariable IPT-weighted Cox model demonstrated no difference in hazard of CDI for vedolizumab vs anti-TNFa (HR 0.33, 95% CI 0.05-2.03) or immunomodulator exposure (HR 1.01, 95% CI 0.41-2.40). Pre-biologic CDI was associated with an increased hazard of CDI (HR 5.95, 95% CI 2.93-12.09). Among patients who developed CDI, 17/43 (39.5%) had pre-biologic CDI a median of 227 days (IQR 160-550 days) preceding CDI.

CONCLUSION

Our study did not identify an increased risk of CDI associated with vedolizumab vs anti-TNFa agents after controlling for UC severity. We hope that these findings will reassure UC providers considering vedolizumab as a first-line biologic agent in the context of gastrointestinal infectious risks.