Fecal microbiota transplantation may be effective in patients with ulcerative colitis

Liz Meszaros, MDLinx

Digestive Disease Week® (DDW)

San Diego, California, United States | May 21-24, 2016


San Diego, CA, May 23, 2016—In patients with resistant active ulcerative colitis, intense multi-donor fecal microbiota transplantation (FMT)—administered via colonoscopy and enema—effectively brought about clinical and endoscopic remission, according to results from the largest controlled trial of FMT presented here at Digestive Disease Week 2016.

Take-home messages

  • Intense multi-donor fecal microbiota transplantation via colonoscopy or enema effectively brought about clinical and endoscopic remission in patients with resistant active ulcerative colitis.
  • Of the 37 patients initially treated with placebo who went on to open-label fecal microbiota transplantation therapy, 27% met the primary endpoint, 46% had clinical remission, and 24% endoscopic remission.

“We conducted this study for two reasons. First, there is a growing understanding now that the gastrointestinal microbiome plays a critical role in health and disease in many conditions, especially in conditions such as ulcerative colitis and Crohn’s disease,” stated Sudarshan Paramsothy, MD, clinical gastroenterologist, University of New South Wales, Australia. “Also, there is a lot of patient interest in exploring microbially-derived therapies, such as FMT, for these conditions. For those reasons, we thought that this was a study that needed to be conducted to help provide some more clarity in this area.”

Dr. Paramsothy and colleagues conducted this double-blind, three-center study, enrolling 81 patients with active UC—which they defined as a Mayo score of 4-10—that was resistant to standard treatments. Patients were randomized to treatment with a single FMT or placebo colonoscopic infusion on day 1, followed by FMT or placebo enemas 5 days per week for 8 weeks.

Each active enema was derived from 3 to 7 unrelated donors, and patients on corticosteroids were weaned from therapy.

Steroid-free clinical remission and endoscopic remission or response—defined as a total Mayo score of ≤ 2 point, with subscores of ≤ 1 for rectal bleeding, stool frequency, and endoscopic appearance, and ≥ 1 point reduction from baseline in endoscopy subscore at week 8—were the primary endpoints.

At the end of blinded therapy, patients treated with placebo were offered the option of 8 weeks of open-label active treatment.

A full 27% of patients treated with FMT achieved the study’s primary endpoint of steroid-free clinical remission and endoscopic remission or response, compared with 8% of placebo patients (P=0.02); steroid-free clinical remission and clinical response rates in FMT versus placebo were 44% vs 20% (P=0.02), and 54% vs 23% (P < 0.01), respectively; steroid-free endoscopic remission rates were 17% vs 8% (P=0.19); and endoscopic response rates were 37% vs 10% (P < 0.01)

In all, 37 patients who were initially treated with placebo went on to open-label FMT, and of these, 27% met the primary endpoint, 46% had clinical remission, and 24% endoscopic remission.

Dr. Paramsothy and colleagues found no differences in adverse events, and only three serious adverse events occurred, including worsening colitis (two active FMT patients and 1 placebo patient).

“FMT therapy is very promising in ulcerative colitis. We’re going to have to refine things a little bit further. This isn’t Clostridium difficile infection, where you’re going to get 90% cure rates, and that regardless of donor, you’re going to have very powerful benefits,” said Dr. Paramsothy. “Ulcerative colitis is a different beast. It’s a multi-factorial condition involving genetic, environmental, microbiological factors that all have a complex interplay to lead to disease. So we’re going to have to be smarter in how we go about treating it.”

He concluded: “In the long term, the ultimate aim would be to hopefully one day be able to use defined microbial consortia, and use that specific to individual patients to treat their condition.”