Multi-donor intense faecal microbiota transplantation is an effective treatment for resistant ulcerative colitis: A randomised placebo-controlled trial

Abstract

Background: The gut microbiota is the antigenic drive in ulcerative colitis (UC), but the efficacy of microbial manipulation using faecal microbiota transplantation (FMT) is unclear. Preliminary low-dose studies in patients with active UC have suggested benefit. The value of such therapy in patients with conventional-drug resistant colitis, the dosing of treatment, and the importance of specific donors are unknown. Methods: In this double-blind, 3-centre study, patients with active UC (Mayo score 4-10) resistant to standard treatments were randomised to receive 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. Patients on corticosteroids underwent mandatory weaning and cessation. The primary endpoint was steroid-free clinical remission together with endoscopic remission or response (total Mayo score ≤ 2 points with subscores ≤ 1 for each of rectal bleeding, stool frequency, and endoscopic appearance, and ≥ 1 point reduction from baseline in endoscopy subscore) at week 8. Secondary endpoints included steroid-free clinical remission (combined total score of ≤ 1 for both rectal bleeding and stool frequency Mayo subscores), clinical response, endoscopic remission (UCEIS score ≤ 1), endoscopic response, quality of life, and safety. All analyses were intention to treat. At blinded therapy conclusion, placebo-treated patients were offered 8 weeks of open-label active treatment. Results: Of 81 patients the primary endpoint of steroid-free clinical remission and endoscopic remission or response was achieved in 11 of 41 (27%) patients receiving FMT vs 3 of 40 (8%) patients receiving placebo (p = 0.02). Steroid-free clinical remission and clinical response rates were 44% vs 20% (p = 0.02) and 54% vs 23% (p < 0.01), respectively. Steroid-free endoscopic remission and endoscopic response rates were 17% vs 8% (p = 0.19) and 37% vs 10% (p < 0.01), respectively. There was no difference in adverse events between the study arms. In the study, 37 patients initially randomised to placebo progressed to open-label FMT, of whom 10 (27%) met the primary endpoint, 17 (46%) experienced clinical remission, and 9 (24%) experienced endoscopic remission, consistent with the blinded FMT outcomes. During blinded therapy, 3 serious adverse events occurred, comprising worsening of colitis (2 active FMT treatment [including 1 patient who required colectomy for severe UC] and 1 placebo). Conclusions: This largest controlled trial of FMT has demonstrated that intense multi-donor colonoscopic and enema FMT is effective in inducing strictly defined clinical and endoscopic remission in patients with resistant active ulcerative colitis.<br />