S730 Vedolizumab Is Associated With Lower Risk of Clostridioides difficile Infection Compared to Anti-TNF Alpha Agents Among Biologic-Naïve Patients With Ulcerative Colitis

Abstract

Introduction: Clostridioides difficile infection (CDI) is a complication of ulcerative colitis (UC) that is associated with poor outcomes. It is unknown if vedolizumab (VDZ), which inhibits lymphocyte trafficking to intestinal mucosa, confers a greater risk of CDI compared to anti-TNF agents. We sought to compare CDI rates between VDZ and anti-TNFs among biologic-naïve patients with UC. Methods: Retrospective cohort study of adult, biologic-naïve UC patients initiating VDZ or anti-TNFs (infliximab or adalimumab) 6/1/14-11/30/20 at a large academic center. Electronic health records were reviewed for clinical data. The primary outcome was time to CDI after biologic initiation, defined by positive PCR or toxin immunoassay with need for CDI treatment. Secondary outcomes were CDI hospitalization and colectomy within 30 days of CDI diagnosis. Inverse probability of treatment weighting (IPTW) was used to adjust for treatment selection bias based on the following variables at/preceding biologic initiation: age, disease duration, systemic corticosteroid use, hospitalization within prior 12 months, Mayo endoscopic subscore, disease extent, and albumin. Kaplan-Meier analysis (KMA) and IPT-weighted Cox regression were used to compare CDI rates by biologic group. Two covariates were included in the weighted Cox model: biologic group and history of pre-biologic CDI. Patients were censored at loss of follow-up, biologic discontinuation, colectomy, or death. Results: 503 UC patients initiated anti-TNFs (n=363) or VDZ (n=140). There was history of pre-biologic CDI in 12.4% of anti-TNF vs 5.7% of VDZ patients (p=0.03) at a median of 167 days (IQR 45, 625 days) prior to biologic initiation (Table 1). Over median follow-up of 425 days after biologic initiation (IQR 154, 959 days), there were 23 cases of CDI (22/363 anti-TNF, 1/140 VDZ, p< 0.01) and 15 CDI hospitalizations (14/363 anti-TNF, 1/140 VDZ, p=0.05). One patient (anti-TNF) required colectomy within 30 days. KMA showed separation in CDI rate curves (p< 0.01, log-rank test) (Figure 1). After IPTW Cox regression, VDZ was associated with a significantly lower hazard of CDI compared to anti-TNFs (HR 0.08, 95% CI 0.01-0.66). Pre-biologic CDI history was associated with greater hazard of CDI (HR 11.38, 95% CI 4.23-30.58). Conclusion: After adjusting for confounders and prior CDI history, VDZ was associated with lower-risk of CDI vs anti-TNFs. This data should be considered when UC patients with history of prior CDI are choosing their first biologic agent.Table 1.: Change in WPAI-CD Scores (Percent Impairment) From Baseline to Week 52 Among Patients Treated With UST or ADA.Figure 1.: Reduction in WPL-associated Costs from Baseline to Week 52 Among Patients Treated With UST or ADA Note: No statistical testing was performed between treatment groups. USD = U.S. dollars.