Colonoscopic Administration of Rebyota Shows Effectiveness for Preventing Recurrent C difficile Infection
Paul Feuerstadt, MD, discusses the safe and effective use of RBL in preventing C difficile recurrence with positive physician feedback and high patient benefit
A phase 3b clinical trial has demonstrated that fecal microbiota, live-jslm (RBL), delivered via colonoscopy is a safe and effective treatment for preventing recurrent Clostridioides difficile infection (rCDI) in adults. The CDI-SCOPE study, presented at Digestive Disease Week 2025, conducted at 12 US sites, enrolled 41 adults with a history of rCDI who had recently completed standard antibiotic therapy.
Participants received a single 150-mL dose of RBL administered to the right side of the colon through colonoscopy. The primary endpoint assessed treatment-emergent adverse events (TEAEs) within 8 weeks or until treatment failure. RBL-related TEAEs were reported in four participants (9.8%), all of which were mild and gastrointestinal in nature. Overall, 18 participants (43.9%) experienced 33 TEAEs, with most categorized as mild (75.8%) or moderate (15.2%). No serious events resulted in intensive care or death.
Treatment success, defined as the absence of CDI recurrence within 8 weeks, was observed in 39 participants (95.1%). Two participants (4.9%) withdrew consent and had indeterminate outcomes.
Physician experience with the procedure was also assessed. Among investigators, 90.2% reported a positive experience with colonoscopic RBL administration, and all physicians rated participant benefit as “much” or “very much” improved.
In an interview, Paul Feuerstadt, MD, FACG, AGAF, associate clinical professor of Medicine at Yale School of Medicine, compared colonoscopic RBL to older forms of fecal microbiota transplantation (FMT). “Really important question. Historically, the way that we did fecal microbiota transplantation was via colonoscopy. We did it in a rudimentary way. We would have a donor come donate that day on site, and we would have the recipients bring their own blender, and we would blenderize it with normal saline. It was actually gross, but it worked,” he said.
With the introduction of Rebyota, he explained, the process has evolved. “This is a broad consortium of microorganisms, spore and non spore forming bacteria, a minimum of 15 million of the Bacteroides,” he noted. Although Rebyota is approved for rectal administration, the study explored an off-label colonoscopic approach.
“If instead of administering via the tube, we use an off-label usage where we cut the bag open, we draw it up into 350 cc syringes, we do a colonoscopy and administer to the right colon, and then allow peristalsis to propulse the material throughout the colon, that might potentially be a more effective way to administer this,” Feuerstadt said. “That was done in a very nice prospective study.”
The open-label study enrolled patients with at least one recurrence of CDI. The average participant age was 61.2 years. Most were women (88%) and White (95%). Of the participants, 43.9% had a first recurrence, and 63% had received vancomycin as their standard of care.
Feuerstadt emphasized that physician satisfaction with the procedure was high. “Physicians, 90.2% of the time, felt positive or very positive about this,” he said. “92.7% felt that the ease of administration was positive or very positive, and 95.1% felt positive or very positive associated with the preparation for the administration.”
When asked about logistical considerations, Feuerstadt noted that approaches varied among sites. “Some actually took the device, the tube, and inserted it from the RBL administrator, the rectal administrator, and tried to put it right into the endoscope or the colonoscope. And that probably worked for some,” he said. “I found it to be easier to clip open or cut open the bag and just draw the material up into the syringes. And that really mimics what we used to do with the historic form of microbiota restoration therapy.”
Among the 41 enrolled participants, 39 completed the study. “We see a safe and effective administration method just giving this overwhelmingly positive feedback from clinicians,” he added.
Looking ahead, Dr. Feuerstadt said the findings may support broader adoption. “Several centers, since Rebyota was FDA approved, have been doing this consistently, but we really didn't have a codified format for this,” he said.
At the DDW2 conference in San Diego, the prospective and retrospective data were presented. “There was investigator-initiated data that showed similar results of 3.8% recurrence rate associated with about 26 individuals who received RBL via colonoscopy,” Feuerstadt reported.
He suggested these findings could empower clinicians. “This should allow local providers, local clinicians, the comfort to say, if I'm a gastroenterologist and I think colonoscopy is appropriate for a patient, it's safe for a patient, this might be a very effective and safe method to use to prevent recurrent C difficile,” he said.
“When we think about colonoscopic administration of Rebyota, this is just another method,” he concluded. “Patients should have access to these heroic measures breaking that cycle of recurrence that so many patients with C difficile go through. If there's another option that patients are more comfortable doing, then that means patients have more access and better availability, and ultimately improving outcomes in a safe and effective way.”
