Intensive 8-week enema treatments had promising results

(MEDPAGE) Intensive treatment with fecal microbiota transplantation (FMT) showed efficacy for ulcerative colitis in patients who were resistant to or intolerant of conventional therapy, a randomized trial found.

A total of 27% of patients given the active treatment met the study’s primary outcome of clinical remission plus endoscopic response or remission after 8 weeks compared with 8% of those who received placebo (P=0.02), reported Sudarshan Paramsothy, MD, of the University of New South Wales in Australia.

In addition, at week 8, steroid-free clinical remission and clinical response rates compared with placebo were 44% versus 20% (P=0.02) and 54% versus 23% (P<0.01), he said at the annual Digestive Disease Week.

“In recent years, researchers have gained a better understanding of the gut microbiota and the critical role it plays in health and disease, including conditions like ulcerative colitis,” Paramsothy said during a press briefing. The estimated prevalence of ulcerative colitis is 200/100,000 adults, according to the CDC.

“The FDA has approved FMT for recurrent Clostridium difficile infection, but questions remain as to whether FMTs could be useful for other types of digestive disorders,” said Beth McCormick, PhD, of the University of Massachusetts Center for Microbiome Research in Worcester, who was not involved in the study. “This randomized, placebo-controlled trial demonstrated promising results for ulcerative colitis, a treatment that hasn’t received FDA approval specifically for this indication, but there’s potential for future progress here,” she said in a press briefing.

“FMT has a lot of promise in ulcerative colitis,” Paramsothy told MedPage Today.

And while the gut microbiota is the antigenic driver in ulcerative colitis, the efficacy of microbial manipulation has not been established, although preliminary low-dose studies suggested potential benefit.

To test FMT in a population of treatment-resistant patients, the authors enrolled 81 patients with active disease, in that Mayo scores were 4 to 10. They were given FMT via a colonoscopic infusion on day 1 and then self-administered FMT enemas 5 days per week for 8 weeks.

“This population is accustomed to using enemas as part of their treatment, so our approach would not be unusual to them,” he said.

The enemas consisted of stool from at least three different donors, to avoid potential “donor effect,” in which the microbial characteristics of a single patients could be unduly influential. Donors are screened to ensure safety of the stool.

Patients were allowed to continue taking immunomodulators such as 5-aminosalicylate and and steroids in doses no higher than 20 mg/day, but had to have stopped previous biologics at least 12 weeks earlier. They also had to stop using any other enema treatments.

The primary endpoint required a Mayo score of 2 or less with subscores of 1 or less for rectal bleeding, stool frequency, and endoscopic appearance, as well as a 1-point or more reduction from baseline on the endoscopy subscore. Clinical remission required a combined total score of 1 or less for the rectal bleeding and stool frequency subscores.

Steroid-free endoscopic remission scores for the FMT and placebo groups were 17% versus 8% at week 8 (P=0.19), while endoscopic response rates were 37% versus 10% (P<0.01).

After the initial 8-week phase, 37 of 40 patients who had been randomized to placebo and went on to receive the active FMT for an additional 8 weeks. Of these, 27% met the primary endpoint, 46% were in clinical remission, and 24% had endoscopic remission.

There were three serious adverse events of worsening of colitis. Two of these were in the active treatment group, with one requiring colectomy, and one in the placebo group.

“We were able to show definitively that fecal microbiota transplantation is an effective treatment for ulcerative colitis. This is important because there are millions of people worldwide seeking alternative treatments for this condition,” Paramsothy said.

The long-term effects of the treatment have yet to be established, he cautioned.

“Future studies should also examine the possible factors leading to effective FMT treatment, such as optimal dosing, as well as the impact of clinical and microbial characteristics of patients and donors,” he stated.

Cost of the treatment is likely to be influenced by the donor screening process, he noted.

See the original news article here.