RESTORE-UC: No better outcomes with FMT superdonors than with autologous stools

The use of superdonor stools for faecal microbiota transplantation (FMT) did not outperform autologous stools in initiating remission in participants with active ulcerative colitis (UC). The current RESTORE-UC trial also presented an FMT anaerobic preparation and administration protocol to improve the international standardisation of this therapy.

Dr Clara Caenepeel (KU Leuven, Belgium) explained that FMT, a novel therapy for active ulcerative colitis, has shown variable success rates in randomised-controlled trials. The results of these trials indicate that the efficacy of FMT may be influenced by donor and procedural characteristics [1]. Therefore, the RESTORE-UC trial (NCT03110289) aimed to assess whether donor preselection on the microbiota level, using a strict anaerobic approach, and repeated FMT administration (4 FMTs) may enhance FMT outcomes in patients with active UC [2]. Superdonors were selected, excluding those with Bacteroides2 enterotype, or those with high proportions of Fusobacterium, Escherichia coli and Veillonella. Donors with the lowest microbial loads were excluded. The enrolled participants were randomised 1:1 to autologous FMT or superdonor FMT. The primary endpoint was steroid-free clinical remission(defined as total Mayo score ≤2, with all subscores ≤1) and steroid-free endoscopic remission (defined as Mayo endoscopy subscore ≤1) after 8 weeks. The results of the 66% futility analysis were presented (n=70).

The primary endpoint was not met. Superdonor stools were not associated with higher rates of steroid-free clinical and endoscopic remission than autologous stools (10.0% vs 13.9%; P=0.72). The secondary endpoints displayed similar results. FMT was in general safe and well tolerated, according to Dr Caenepeel. In total, 76.9% and 23.1% of the participants experienced adverse events (AEs) in the autologous arm and the superdonor arm, respectively. Two serious AEs were reported, 1 case of dysuria and 1 case of worsening colitis. Both of these events occurred in the autologous arm.

Dr Caenepeel argued that the negative results of this trial need to be investigated thoroughly. “Perhaps the endpoint we chose for this study was too bold. However, it could be that our perspective on donor selection is still too simplistic. Therefore, I believe that future studies should assess factors other than microbiota, such as immunity and genetics.”

1. Sun D, et al. Medicine. 2016;95(23):e3765.
2. Caenepeel C, et al. Standardized faecal microbiota transplantation with microbiome-guided donor selection in active UC patients: A randomized, placebo-controlled intervention study. OP03, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024