SAN DIEGO – When fecal transplants don’t work for ulcerative colitis, it’s probably because they aren’t used often enough, according to investigators from the University of New South Wales, Sydney.
The researchers made sure that wasn’t the case in their own double-blind trial, the largest to date of fecal microbiota transplantation (FMT) for ulcerative colitis. Forty-one patients with active, mild to moderate disease (Mayo score 4-10) that was resistant to standard medications were randomized to 150-mL, self-administered fecal enemas 5 days a week for 8 weeks, and 40 others to placebo enemas. Patients were tapered off steroids at study entrance, and each FMT patient received stool from 3-7 unrelated donors.
Steroid-free clinical remission and endoscopic remission or response were achieved in 11 FMT patients (27%), compared with 3 (8%) placebo patients (P = .02). A total of 18 treated patients (44%) and 8 placebo patients (20%) had steroid-free clinical remissions, while 22 treated patients (54%) and 9 patients in the placebo group (23%) had some type of positive clinical response (P less than .01).
Patients were in their mid-30s, on average, with disease durations of about 6 years. More than half were men. About one-quarter were on oral steroids, and more than half were on oral 5-aminosalicylic acid medications, which were allowed during the study. Almost half were on methotrexate or other oral immunomodulators, which were also allowed. Patients were excluded if they had been on a biologic in the previous 12 weeks.
Afterward, 37 patients in the placebo arm opted for open-label FMT. Results were similar, with steroid-free clinical remission and endoscopic remission or response in 10 patients (27%), clinical remission in 17 (46%), and endoscopic remission in 9 (24%).
The anatomical extent of disease did not affect outcome, but patients with more severe endoscopic disease and those on steroids at study entrance didn’t do as well. Three patients flared during the trial, one in the placebo arm and two in the FMT arm, one of whom required colectomy.
The investigators were surprised by the magnitude of the benefit, given the mixed results in previous investigations with less frequent dosing. But they were not surprised that FMT worked.
“In ulcerative colitis, the microbiota appear to be the antigenic driver, so it makes sense that correcting the disturbance” helps, said lead investigator Dr. Sudarshan Paramsothy, a gastroenterologist at the University of New South Wales.
Dr. Paramsothy and his colleagues have a hunch they can do even better. They are looking into the microbiologic factors of donors and patients that influence response, with the ultimate goal of matching the best donor to the best patient. They’re examining maintenance therapy, too; “it’s one thing to induce remission, it’s another thing to maintain remission,” Dr. Paramsothy said.
In an interview at the annual Digestive Disease Week, he explained the technique, the thinking behind it, future directions, and how to counsel patients in light of the findings.