Results from a randomized controlled trial showed fecal microbiota transplantation safely induced remission in patients with active ulcerative colitis.
Aiming to evaluate the safety and efficacy of FMT for treatment of active UC, Paul Moayyedi, MD, from McMaster University in Ontario, and colleagues performed a placebo-controlled, double-blind, randomized, parallel study. Adult participants were randomly assigned to receive 50-mL FMT from healthy anonymous donors (n = 38) or placebo (50 mL water; n = 37) via retention enema once a week for 6 weeks. Stool samples were collected weekly prior to enema for microbiome analysis, flexible sigmoidoscopy was performed at baseline and week 7, and the primary study outcome was remission at week 7.
The trial was stopped early for futility, but patients already enrolled were allowed to complete the trial. Of the 70 patients who completed the trial, 24% of the FMT group compared with 5% of the placebo group were in remission at week 7 (17% difference; 95% CI, 2%-33%) with comparable adverse events. Of the nine patients in remission after FMT, seven received FMT from a single donor. Of the four patients with UC for 1 year or less, three achieved remission, and of the 34 patients with UC for more than 1 year, six achieved remission (P = .04). Patients in the FMT group had greater diversity in their stool microbial composition vs. baseline compared with patients in the placebo group (P = .02).
“This is the first randomized, placebo-controlled trial, to evaluate the efficacy of FMT in active UC and suggests that this approach induces remission in a statistically significant proportion of cases,” the authors wrote. “FMT may be more efficacious in patients with a recent diagnosis of UC, and this is biologically plausible, as a perturbation in the microbiome might be more easily restored early in the course of the disease. The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and other have had disappointing results.”
Colleen R. Kelly
In a related editorial, Ari M. Grinspan, MD, from Icahn School of Medicine at Mount Sinai in New York, and Colleen R. Kelly, MD, from Brown University, explored the reasons why another recent randomized controlled trial of FMT for UC (Rossen, et al) was negative while this one was positive. First, Moayyedi and colleagues administered a higher number of FMTs per patient and via the lower rather than upper gastrointestinal route. “The upper GI route might render the active constituent of FMT ineffective by the time it reaches the diseased colon. It is also possible that there is a dose response or a threshold required for engraftment to be attained to alter effectively the gut microbiome and the downstream inflammatory cascade,” they wrote. Moayyedi’s study also permitted anti-tumor necrosis factor treatment, “and those subjects on immunosuppression did better, raising the question as to whether immune factors may have a role in successful FMT induction. These uncertainties make our ignorance clear; we still do not understand the active component of FMT.”
Grinspan and Kelly concluded that for IBD, “based on the current data, FMT should remain in clinical trials and not clinical practice.” – by Adam Leitenberger
Disclosure: Moayyedi reports he is a chair partly funded by an unrestricted donation given to McMaster University by AstraZeneca, and he has received honoraria for speaking and/or serving on the advisory board for AstraZeneca, Actavis and Shire. Grinspan reports he received research support from the Sinai Ulcerative Colitis Clinical, Experimental and System Studies. Kelly reports she has served as a consultant and site investigator for Seres Health and received research support from Assembly Biosciences.