OP15 Faecal microbiota transplantation for active Crohn’s disease: The MIRO (Microbial Restoration) randomised placebo-controlled trial.

Abstract Background The enteric microbiota is the antigenic drive in Crohn’s disease, making microbial manipulation with faecal microbiota transplantation (FMT) a therapeutic option. However there are no data supporting its use in active Crohn’s disease. Methods This study assessed FMT therapeutic efficacy and safety in active Crohn’s disease. This randomised, double-blind, placebo-controlled trial in patients with active Crohn’s disease (CDAI 220-450) had an initial three week “optimisation” of wholefood diet and one-week antibiotic therapy. Patients were then randomised to single-donor anaerobically-prepared FMT or placebo (2:1) for eight weeks by gastroscopy at weeks 0, 2, 6 (disease proximal to splenic flexure), or colonoscopy followed by weekly enemas (left-sided colonic disease). Primary endpoint was clinical response at week 8 defined by a CDAI decrease of ≥ 100 points or CDAI to < 150. Modified intention-to-treat (mITT) analysis included patients receiving ≥1 dose of FMT or placebo, per protocol (PP) analysis for those who completed eight weeks of treatment. Results Patient outcomes: Of 103 patients enrolled, 70 received FMT and 33 placebo. 95 had upper and 8 lower gastrointestinal delivery. Before FMT/placebo, the CDAI response to diet and antibiotics occurred in 21% of all patients. Primary outcome of clinical response at week eight: mITT FMT 40/70 (57.1%) vs placebo 15/33 (45.5%) (P = 0.296); PP analysis: FMT 40/63 (63.5%) vs placebo 14/30 (46.7%) (P = 0.177). Decrease in CDAI was significant only in the FMT group (P < 0.001; Image I). Endoscopic response: total SES-CD decrease of 25% or to SES-CD ≤2 was more likely with FMT 24/45 (53.3%) vs placebo 4/17 (23.5%) (P = 0.047). Significant improvement in SES-CD occurred only in the FMT group (P = 0.031). Decrease in biomarkers of inflammation CRP and faecal calprotectin did not differ between treatment groups. Donor Effect: A substantial donor effect was demonstrated, with patient clinical response rates for the 5 donors 43%, 50%, 55%, 78% and 93% (P = 0.02) and endoscopic response ranging from 31% to 70% (P = 0.27). Adverse events: Majority mild transient gut symptoms and liver function test abnormality. Conclusion Faecal microbiota transplantation (FMT) for active Crohn’s disease was therapeutically more effective than placebo. Endoscopic response, a more objective parameter, significantly improved only with FMT therapy. There was a profound variation in donor therapeutic potency. The final lack of CDAI significance likely related to the large diet and antibiotics effect pre randomisation, and donor variation effect. FMT for Crohn’s disease has a promising therapeutic role. Conflict of interest: Fehily, Sasha: No conflict of interest Wright, Emily Kate: No conflict of interest Bogatic, Damjana: No conflict of interest Wilson-O’brien, Amy: No conflict of interest Basnayake, Chamara: No conflict of interest Stanley, Annalise: No conflict of interest Marks, Elise: No conflict of interest Russell, Erin: No conflict of interest Rong, Yuwei: No conflict of interest Gory, Ilana: No conflict of interest Ardalan, Zaid: Crohn’s colitis Australia Angela McAvoy Fellowship recipient 2025 GENIUS Research grant Hamilton, Amy: No conflict of interest Morrison, Mark: No conflict of interest Thompson, Alexander: No conflict of interest Bryant, Robert Venning: No conflict of interest Costello, Samuel Paul: No conflict of interest Kamm, Michael Albert: No conflict of interest