Fecal Therapy Via Colonoscopy Found Safe and Effective for Recurrent C. Diff

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Benefits held for up to 2 months and adverse events were mainly mild GI ones

by
Tara Haelle, Contributing Writer, MedPage Today
May 4, 2025 • 3 min read

SAN DIEGO — Administering fecal microbiota via colonoscopy instead of rectally prevented recurrence of Clostridium difficile (C. diff) for up to 2 months with no major safety signals, according to a phase IIIb study.

Treatment with live-jslm (Rebyota) was successful in preventing recurrent C. diff infection for the next 8 weeks in 95% of participants (95% CI 83.5-99.4%), with 9.8% of the participants reporting adverse events (AEs), all mild and gastrointestinal, said Sahil Khanna, MBBS, of the Mayo Clinic in Rochester, Minnesota, at the annual Digestive Disease Week (DDW). The data were simultaneously published in Therapeutic Advances in Gastroenterology.

Two patients’ outcomes were indeterminate after they dropped out for a scheduling conflict and unrelated development of a brain neoplasm, though neither reported C. diff symptoms up until withdrawal.

“I think it’s really important for us in clinical practice to have this information,” commented Jessica R. Allegretti, MD, MPH, of Brigham and Women’s Hospital in Boston, who was not involved in the study. “I find, at least in my practice, there is a patient preference towards colonoscopic administration.”

Rebyota is a fecal microbiota live-jslm product approved by the FDA for preventing recurrent C. diff infection in the form of a single 150 mL dose administered rectally. Data from more than 1,500 participants in seven previous studies has shown Rebyota was 71-74% effective in preventing recurrent C. diff infection at 8 weeks with a favorable safety profile, Khanna told attendees. But administering it via colonoscopy would allow for targeted delivery and assessment of colonic mucosa and easier integration into routine gastroenterology clinical practice, he said.

The researchers enrolled 41 adults with documented recurrent C. diff infection in a prospective, single-arm trial at 12 sites. All the participants had completed at least 10 consecutive days; had no more than 60 total days of antibiotic treatment; and had controlled C. diff diarrhea for at least 2 consecutive days. After a 24-72-hour antibiotic washout period, the participants completed a bowel preparation for colonoscopy. All participants except one received a 150 mL dose in the right colon via colonoscopy.

The participants were mostly white (95%) females (88%) with an average age of 61 and an average BMI of 26. They had an average of 3.2 previous C. diff episodes, including 24% who had had>3. Their most recent episode lasted an average 24 days, and all had been prescribed antibiotics during their last episode, primarily vancomycin (63%) or fidaxomicin (35%).

The five AEs reported by four patients within 8 weeks of administration included abdominal distention, constipation, diarrhea, and flatulence. Additional AEs over the next 6 months were reported by 44% of participants, predominantly GI (22%) or infections (15%), and were mostly mild or moderate. Two patients had serious AEs, including one brain neoplasm and one diagnosis of inflammatory bowel disease, that were both determined to be unrelated to the intervention.

“The safety findings were consistent overall with what we see in microbiota-based therapeutics,” Khanna said. In a separate DDW poster that reported findings on physician experiences with the procedure, 90% of investigators reported a “positive” or “very positive” experience across all aspects of administration. One respondent reported a “somewhat negative” experience involving connecting Rebyota to colonoscopes.

Trial limitations included the single-arm open-label design and a small sample size that limited generalizability.

Noting the “very impressive success rate,” Allegretti asked Khanna whether there was benefit then in right-sided administration with the colonoscopy compared to the more traditional rectal administration. Since it was an open-label study where all patients except one received Rebyota in the right colon, the study could not answer whether right or left was better, and they don’t have data on subsequent recurrent C. diff infections out to 6 months yet, he replied.

Khanna added that a key aspect of enrollment was ensuring that patients truly had a C. diff infection, and the trial was designed to simulate real-world practice. All the patients had chosen a colonoscopy as the method of administration from multiple options, and none showed reluctance, he said.