Fecal microbiota transplantation (FMT) was effective in reducing symptoms of ulcerative colitis (UC) and inducing healing of the digestive tract in patients who were resistant to or intolerant of other treatments. The randomized trial, reported at the 2016 Annual Digestive Disease Week, looked at 8 weeks of treatment aimed at inducing remission. Longer-term data are needed to determine the effect of FMT on maintaining remission.
FMT is currently used to treat Clostridium difficile infection. This study extends the potential use of this approach in UC.
“Multi-donor FMT aims to treat the underlying microbial disturbances associated with UC, instead of just the symptoms. This is unlike the usual treatment with immunotherapies,” explained lead author Dr. Sudarshan Paramsothy in a teleconference in advance of the annual Digestive Disease Week.
Dr. Sudarshan Paramsothy
“This is the first multicenter clinical trial to use an intense therapy of FMT infusions – 40 over 8 weeks – and it has been able to show definitively that FMT is an effective treatment for ulcerative colitis. This is important, because there are millions of people worldwide seeking alternative treatments for their condition,” said Dr. Paramsothy, a gastroenterologist from the University of New South Wales, Australia.
The study enrolled 81 patients with active disease and treatment-resistant or intolerant UC across three different study sites in Australia. Patients were randomized to intense FMT (n = 41) or placebo (n = 40). The first treatment was given through a colonoscope; subsequently, enemas were self-administered 5 days a week for 8 weeks.
Patients in the study were allowed to be on treatment for UC, with the exception of biologics, which had to be suspended at least 12 weeks prior to enrollment in the trial.
Dr. Paramsothy pointed out that patients with UC are accustomed to using enemas as part of treatment, so FMT would be acceptable to them.
“The enemas in this trial were as well tolerated as other types of enemas,” he noted.
After 8 weeks, more than three times as many patients in the FMT group versus placebo reported steroid-free clinical remission (symptom relief) and had endoscopically determined healing/improvement of the digestive tract lining: 11 of 41 patients (27%) in the FMT group versus 3/40 (8%) in the placebo group, a statistically significant difference (P = .02). When steroid-free clinical remission (symptom-free) status was assessed, 44% of the FMT group versus 20% of controls met this endpoint (P = .02).
At week 8, clinical response was seen in 54% of the FMT-treated group versus 23% of the control group (P less than .01).
No difference between the two study arms was seen in the rate of adverse events.
Thirty-seven patients initially assigned to placebo went on to receive open-label FMT; of these, 10 (27%) were both symptom-free and endoscopically improved, 17 (46%) had clinical remission, and 9 (24%) had endoscopic remission.
This study utilized FMT from at three to seven unrelated donors to minimize the potential for a “donor effect,” in which outcomes may be determined by the microbial characteristics of a single donor.
Future studies will look at potential factors in the microbiota that influence response, optimal dosing, and the impact on response of clinical and microbial factors in patients. An important area of research is how best to match patients and donors.
“We are conducting microbial studies to ascertain why some patients respond and others don’t,” he noted. “We are also studying how to optimize selection of donors based on microbial profile. Depending on the recipient, a different microbial profile might be better.”
Studies of the longer-term effect of FMT in UC are needed. It is not known if FMT improves sensitivity to biologics or other treatments.
Another concern is whether FMT changes the microbiome and makes patients more susceptible to infection or other morbidities. “There is a push for registries to follow patients [treated with FMT] long term,” he said.
Dr. Paramsothy received funding from the Broad Medical Research Program at the Crohn’s & Colitis Foundation of America, the Gastroenterological Society of Australia, and the Mt. Sinai Hospital New York (SUCCESS fund) for this research. Study infusions were supplied by the Centre for Digestive Diseases, Sydney.