Fecal Microbiota Treatment via Colonoscopy Safe, Effective for Recurrent C. Diff, Study Suggests

Colonoscopic administration of fecal microbiota, live-jslm (FMBL; Rebyota) is safe and effective for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults who have received antibiotic treatment, according to findings of an exploratory phase 3b open-label study presented at Digestive Disease Week 2025, May 3-6, in San Diego.

The single-arm study, conducted at 15 US sites, enrolled 73 participants and reported a treatment success rate of 82.2% at 8 weeks following a single administration. Among those who achieved initial treatment success, 94.9% maintained a sustained clinical response at 6 months, according to the findings.

Sahil Khanna, MBBS

Courtesy of Mayo Clinic

First author Sahil Khanna, MBBS, associate professor of medicine, division of gastroenterology and hepatology at the Mayo Clinic in Rochester, MN, and colleagues defined the primary endpoint, treatment success, as the absence of CDI diarrhea without the need for retreatment for CDI at 8 weeks post-FMBL administration. The 82.2% (60/73; 95% CI, 71.1–90.0) treatment success rate aligned closely with rates observed in previous preliminary FMBL studies, reinforcing the consistency of the therapy’s effectiveness. Investigators reported that of the 13 participants who did not achieve treatment success, 6 (46.2%) did not experience a CDI event but received CDI treatment outside protocol-specified criteria.

Treatment success rates were higher among participants who received the full dose of FMBL, administered as approximately 150 mL of thawed product into the cecum or terminal ileum. In this subgroup, the success rate reached 85.2% (52/61). The full dose was defined as 3.0 × 10^11 to 3.5 × 10^11 colony-forming units of live microbes. Twelve participants received a partial dose due to administration difficulties/

Adverse events (AEs) occurred in 65.8% (48/73) of participants, with treatment-related AEs reported in 19.2%. The most common treatment-related AEs were flatulence (5.5%), diarrhea (4.1%), and abdominal pain (4.1%). "The majority of AEs were mild or moderate in severity," the authors noted. Severe AEs occurred in 9.6% of participants, but none were deemed related to FMBL. No deaths were reported during the study.

Of the 73 participants, 68 completed the 6-month follow-up. The cumulative incidence of CDI recurrence among initial treatment successes was 5.1% (3/59) at 6 months. "The study demonstrated that FMBL, administered by colonoscopy, is well tolerated and effective for preventing rCDI," the authors wrote, adding that the observed durability of response highlights the therapy’s long-term potential.

Khanna et al also noted that study physicians overall regarded colonoscopic administration of FMBL positively "both in relation to the benefits for participants and the practicality of the administration process within the CDI-SCOPE
trial. Physician participants said they had only minimal challenges administering FMBL via colonoscopy and that the ease of the procedure provides an additional benefit, particularly for elderly patients, who may retain treatment more easily when administered this way vs rectally, authors stated.

Eligible participants were adults aged 18 years or older with a diagnosis of rCDI, defined as at least one recurrence after a primary CDI episode. Participants had to have completed at least one course of antibiotic treatment for CDI and exhibited a clinical response to that treatment. The final cohort was predominantly White (95.1%) and 87.8% were women. Mean age was 61.2 years and mean number of previous CDI episodes was 3.2 with the most recent having lasted approximately 24 days. The majority of participants had not been hospitalized during their last episode.

The authors acknowledged several limitations. The single-arm, open-label design limited the ability to compare outcomes directly to a control group. The relatively small sample size and lack of microbiome analyses precluded detailed exploration of microbiome changes as a mechanism of action. Additionally, the study population may not fully represent the broader rCDI patient population, as patients with severe underlying disease or immunocompromised states were underrepresented.

"The findings of this study support the use of FMBL administered by colonoscopy as an effective and well-tolerated treatment option to prevent rCDI in adults," the authors concluded.

References

Safety and effectiveness of fecal microbiota, live-jslm (REBYOTA®) administered by colonoscopy for prevention of recurrent Clostridioides difficile infection: 8- week results from CDI-SCOPE, a single-arm, phase IIIb trial. Ther Adv Gastroenterol. 2025;18:1-12. doi:10.1177/
17562848251339697