By Shazia Qureshi
AMSTERDAM, the Netherlands -- March 20, 2016 -- Multi-donor fecal microbiota transplantation (FMT) provided higher rates of clinical remission and endoscopic response, compared with placebo, in patients with active ulcerative colitis, according to a study presented here on March 18 at the 11th Congress of the European Crohn’s and Colitis Organisation, Inflammatory Bowel Diseases (ECCO-IBD).
“The gut microbiota is the antigenic drive in ulcerative colitis, but the efficacy of microbial manipulation using FMT is unclear,” said Sudarshan Paramsothy, MD, St. Vincent’s Clinical School, University of New South Wales, Sydney, Australia.
The study included 81 patients with active ulcerative colitis of >3 months’ duration. Disease was mild to moderate (Mayo score 4-10, and an endoscopy subscore of ≥1), and of any extent except distal proctitis
Patients were randomised (1:1) to treatment with either FMT or placebo for 8 weeks. Both were administered initially as a single colonoscopic infusion on day 1, and then by enema 5 days per week for 8 weeks. Each FMT enema was derived from 3 to 7 unrelated donors who were healthy and had been pre-screened (stool, blood, and serology). Each patient’s FMT was sourced from a single group of donors. Both FMT and placebo were frozen using glycerol cryoprotectant. All analyses were by intention to treat.
The primary endpoint was defined as steroid-free clinical remission plus endoscopic remission or response at week 8. This meant a total Mayo score of ≤2 with subscores of ≤1 for rectal bleeding, stool frequency, and endoscopic appearance, as well as a drop of ≥1 point from the baseline endoscopy subscore.
The investigators found that 27% of FMT-treated patients reached the primary endpoint at week 8, compared with 8% of patients on placebo (P = 0.02).
Steroid-free clinical remission, which was defined as a combined total score of ≤1 for both Mayo subscores for rectal bleeding and stool frequency, were achieved in 44% of patients in the FMT group, compared with 20% in the placebo-treated group (P = .02). Clinical response was noted for 54% and 23% of patients respectively (P
Steroid-free endoscopic remission, defined as a score of ≤1 on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), occurred in a higher proportion of FMT-treated patients compared with placebo, but this was not significant (17% vs 8%; P = .19). Endoscopic response, in contrast, did differ significantly between the 2 groups (37% vs 10%; P
The most common adverse events (AEs) were abdominal pain, bloating, and flatulence. In terms of serious AEs, 3 cases of worsening of colitis were reported. Two of these were in the FMT arm (including 1 patient who underwent colectomy for severe ulcerative colitis), plus 1 patient in the placebo arm.
Among patients with pancolitis, a higher proportion of patients treated with FMT reached the primary endpoint compared with placebo (4/9 vs 0/12; P = 0.01). Patients with the most severe endoscopic severity (Mayo score of 3) did not reach the primary endpoint.
“Intense multi-donor FMT therapy is effective in inducing clinical remission and endoscopic improvement or remission in patients with active ulcerative colitis, many of whom were resistant to standard drug therapy,” Dr. Paramsothy concluded.
[Presentation title: Multi-Donor Intense Faecal Microbiota Transplantation Is an Effective Treatment for Resistant Ulcerative Colitis: A Randomised Placebo-Controlled Trial. Abstract OP017]
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