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OP017 Multi-donor intense faecal microbiota transplantation is an effective treatment for resistant ulcerative colitis: a randomised placebo-controlled trial

S. Paramsothy*1, M. Kamm2, 3, A. Walsh4, J. van den Bogaerde5, D. Samuel6, R. Leong6, S. Connor7, W. Ng7, R. Paramsothy7, N. Kaakoush8, H. Mitchell8, W. Xuan9, E. Lin10, T. Borody10

1University of New South Wales, St Vincent’s Clinical School, Sydney, Australia, 2St Vincent’s Hospital, Melbourne, Australia, 3Imperial College London, London, United Kingdom, 4St Vincent’s Hospital, Sydney, Australia, 5Nambour General Hospital, Nambour, Australia, 6Bankstown-Lidcombe Hospital, Sydney, Australia, 7Liverpool Hopsital, Sydney, Australia, 8University of New South Wales, School of Biotechnology & Biomolecular Sciences, Sydney, Australia, 9Ingham Institute, Sydney, Australia, 10Centre for Digestive Diseases, Sydney, Australia

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).

Conclusion

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.