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P591 Low donor microbial engraftment after combined endoscopic and oral faecal microbiota transplant (FMT) in patients with antibiotic dependent pouchitis

H. Herfarth*1, E. L. Barnes1, M. D. Long1, K. L. Isaacs1, T. Leith2, M. Silverstein3, Y. Gerardin3, Z. Kassam3

1University of North Carolina, Medicine, Chapel Hill, USA, 2OpenBiome, Somerville, MA, USA, 3Finch, Somerville, MA, USA

Background

A significant number of pouch patients develop antibiotic dependent pouchitis (ADP) after ileo-anal pouch anastomosis. Microbial dysbiosis, which can only be controlled with antibiotics, is thought to be a major driver of clinical symptoms in ADP. The objective of this placebo-controlled proof-of-concept faecal microbiota transplant (FMT) study was to evaluate safety, efficacy and donor microbial engraftment of an intensified FMT approach in patients with ADP.

Methods

Patients with ADP (defined by the continuous need for antibiotic therapy to control symptoms) in clinical remission as defined by a modified pouch activity index < 4 were randomised to either active endoscopic FMT (eFMT=24 g FMT) or placebo eFMT followed by daily active encapsulated oral FMT (oFMT; 6 FMT capsules/day=4.2 g FMT) or identical placebo capsules for 14 days. Antibiotics were discontinued before randomisation. In case of relapse patients could participate in an open-label active eFMT and oFMT. FMT and matching placebo were provided by a stool bank (OpenBiome). Endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of faecal calprotectin (FCP) and engraftment of donor FMT. For engraftment analyses, 16S rRNA sequencing of stool samples collected before and after FMT was performed.

Results

Six patients were randomly assigned to receive active or placebo FMT. All patients experienced relapse with increase of diarrhoea and urgency either during or shortly after completion of FMT. Five patients continued with open-label active FMT and 80% (4/5) experienced a relapse with concomitant increase of FCP during or shortly after completion of FMT. No FMT-related safety events were observed. Due to the unexpected low efficacy of FMT, the steering committee decided to halt enrolment to assess for FMT engraftment. FMT engraftment was sustained in 1 out of 6 subjects (Figure 1). This patient (1028) did not relapse and remained off of antibiotics for the study period of 16 weeks.

Engraftment of active donor endoscopic followed by oral FMT in 6 patients in the randomised or open-label portion of the trial. Three patients received active FMT twice in both portions of the trial.

Conclusion

Low donor FMT engraftment is the most likely reason for the low clinical efficacy of FMT in this pilot study in patients with ADP. Thus, before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis it is mandatory to explore approaches for superior FMT engraftment. This study was funded by Litwin IBD Pioneers Initiative.