Damian McNamara

March 21, 2016

AMSTERDAM — For patients with treatment-resistant ulcerative colitis, fecal microbiota transplantation is effective at inducing steroid-free clinical remission at 8 weeks, according to results from a double-blind, multicenter trial.

"This study is important as it represents the largest and most intensive trial of fecal microbiota transplantation for ulcerative colitis," Sudarshan Paramsothy, MD, from the University of New South Wales in Kensington, Australia, told Medscape Medical News.

Dr Paramsothy presented the study results here at the European Crohn's and Colitis Organisation 2016 Congress.

Forty-one adults were treated with an initial fecal microbiota transplantation, delivered by colonoscopy, followed by five active enemas per week for 8 weeks, performed by the patient at home. Forty adults received placebo.

During an 8-week open-label study extension, 37 people in the placebo group chose to switch to the fecal microbiota regimen.

Each 150 mL of fecal microbiota contained previously frozen stool from three to seven unrelated donors.

"We used this multidonor concept for logistical reasons because of the number of infusions required for this trial," Dr Paramsothy reported. The team also wanted to prevent patients from receiving an infusion from a single bad donor. The donor recruitment and selection process has already been described elsewhere (Inflamm Bowel Dis. 2015;21:1600-1606).

All patients presented with active mild to moderate ulcerative colitis (Mayo score, 4 - 10). Steroids were permitted, but were tapered to zero during the study period. The primary combined end point was endoscopic response on flexible sigmoidoscopy and clinical remission and response at 8 weeks and 16 weeks.

Table: Outcomes at 8 Weeks

Outcome Fecal Microbiota Group, % (n = 41) Placebo Group, % (n = 40) P Value
Clinical remission 44 20 .02
Clinical response 54 23 <.01
Endoscopic remission 17 8 .19
Endoscopic response 37 10 <.01
Clinical remission plus endoscopic remission and response 27 8 .02

 

Of the patients who switched from the placebo to the fecal microbiota group, 27% met the primary combined end point at week 16.

There were no significant differences in the number or type of adverse events between the two groups, Dr Paramsothy reported. Self-limiting gut symptoms included abdominal pain and flatulence. Three patients experienced serious adverse events during the first 8 weeks; colitis worsened in two patients in the fecal microbiota group and in one in the placebo group.

Intensive fecal microbiota transplantation "appears to be effective for remission induction in mild to moderate ulcerative colitis resistant to standard medical therapies," Dr Paramsothy told Medscape Medical News.

"Considerable Safety Questions"

"We have considerable safety questions," said session moderator Philippe Seksik, MD, PhD, from Hôpital Saint-Antoine in Paris. "With a single donor, there can be a strong donor effect, but you have a lower risk of transmission [of something unwanted]. Multidonor transplants avoid this single-donor effect, but also increase the risk of transmission," he told Medscape Medical News.

An immune-modulated disease caused by the microbiota is another potential concern, Dr Seksik said. Ideally, he said, he would like to see multidonor samples kept frozen for months while donors are monitored for any health issues. The ultimate goal is to identify the "exact consortia of bacteria that are beneficial in this population" and to administer only that to patients.

The US Food and Drug Administration just announced its intention to increase the regulation of fecal microbiota transplantation to promote greater safety and availability for patients. Currently, the procedure is only cleared for the treatment of Clostridium difficile infection.

"What we didn't have from this study is a lot of the microbiology analysis," said Ailsa Hart, PhD, from St. Mark's Hospital in London, United Kingdom.

This information could help identify the most effective strains. Multidonor transplantations "are another piece of the puzzle. There are quite a number of studies on this underway now. It looks exciting, but we need more study," she told Medscape Medical News.

Dr Paramsothy reports receiving grants from Abbott/GESA IBD Clinical Research, the Broad Medical Research Program, the Sunshine Coast Wishlist Research Grant Scheme, the UNSW Gold Star Award, and the National Health and Medical Research Council Medical Postgraduate Research Scholarship. Dr Seksik and Dr Hart have disclosed no relevant financial relationships.

European Crohn's and Colitis Organisation (ECCO) 2016 Congress: Abstract OP017. Presented March 18, 2016.

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