Safety and Efficacy of Fecal Microbiota, Live-jslm to Prevent Recurrent Clostridioides difficile Infection in Participants With Irritable Bowel Syndrome

Introduction: The safety and efficacy of microbiota-based products in patients with irritable bowel syndrome (IBS) and recurrent Clostridioides difficile infection (rCDI) has not been studied. Fecal microbiota, live-jslm (RBL; REBYOTA^®) is an FDA-approved, single-dose, microbiota-based product to prevent rCDI in adults following standard-of-care (SOC) antibiotic treatment. This was an exploratory subgroup analysis of PUNCH CD3-OLS, a phase 3, open-label, prospective study conducted in the United States (US) and Canada, to evaluate the safety and efficacy of RBL in participants with documented rCDI and concurrent IBS. Methods: Participants aged ≥ 18 years with a diagnosis of rCDI and who completed SOC antibiotic treatment were enrolled in this study. The primary endpoint of PUNCH CD3-OLS was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success at 8 weeks and sustained clinical response at 6 months. In this subgroup analysis, ongoing IBS was confirmed based on medical record documentation at the time of RBL administration. Results: Among the 697 RBL recipients, 90 had comorbid IBS. After RBL administration, 52 participants with IBS (57.8%) and 278 participants without IBS (45.8%) experienced TEAEs through 8 weeks. Most TEAEs were mild (22.2% with IBS, 20.1% without IBS) or moderate (26.7% with IBS, 18.8% without IBS). Serious TEAEs were reported by 1 participant with IBS (pneumonia reported to be unrelated to RBL) and 26 participants without IBS [most of which were related to preexisting conditions (3.1%)]. Among all participants, 68.9% with IBS and 75.6% without IBS had absence of CDI diarrhea through 8 weeks after RBL administration. Of the participants with treatment success, 82.3% with IBS and 92.2% without IBS had sustained clinical response through 6 months. Conclusion: RBL is a safe and efficacious option to prevent CDI recurrence in patients with concurrent IBS. Trial registration: ClinicalTrials.gov identifier, NCT03931941.