36 ANTIBIOTIC PRETREATMENT PRIOR TO FECAL MICROBIOTA TRANSPLANTATION INCREASES RATES OF REMISSION IN PATIENTS WITH MILD TO MODERATE ULCERATIVE COLITIS: RESULTS FROM A PILOT RANDOMIZED CLINICAL TRIAL

Introduction:Several randomized controlled trials have demonstrated efficacy of fecal microbiota transplantation (FMT) in treatment of ulcerative colitis (UC).However, optimal delivery modality and role of antibiotic pre-treatment remain to be determined.We report interim analysis of a randomized trial aimed at assessing FMT with and without antibiotic pre-treatment and FMT maintenance with capsules versus enema in patients with active mild-moderate UC.Methods: We conducted a 2x2 factorial randomized clinical trial of FMT in patients with mild to moderate UC(total Mayo score 4-9).Participants received single FMT(250mL) by colonoscopy for induction.Prior to initial FMT, subjects were randomized into four arms: 1)pre-treatment antibiotics(neomycin,vancomycin and metronidazole 500mg BIDx5 days;ABX) + FMT capsule maintenance(30 capsules weeklyx6 weeks); 2)No ABX+FMT capsule maintenance; 3)ABX+FMT enema maintenance(60mL weekly x 6 weeks); 4)No ABX+FMT enema maintenance.Primary outcome was week 8 steroid free remission(total Mayo£2+endoscopic improvement);safety profile was examined.Secondary outcomes included clinical response(improvement total Mayo ‡3) and improvement in abdominal pain.Stool samples were obtained prior to FMT, once weekly during maintenance and 1 month and 3 months after completion for whole genome sequencing.Results: For this interim analysis, 25 patients have enrolled (Table 1).Across all arms, 32% achieved the primary endpoint (p=0.003).42% demonstrated clinical response(p=0.0002).44% reported improved abdominal pain(p=0.009).No serious adverse events occurred.Those who received ABX were significantly more likely to achieve steroid free remission(55% v. 14%, p=0.04).There was no statistically significant difference between maintenance delivery modality(capsule 45% vs enema 21%, p=NS).ABX + FMT capsule maintenance arm had the highest rate of remission(figure 1a).Secondary outcomes did not vary by ABX or maintenance delivery modality.Based on taxonomic analysis of metagenomic reads, composition of most patients' fecal community became substantially more similar to their donor during maintenance regimen than at baseline (Wilcoxon's signed-rank test: p=0.003) and this was maintained through 3 months follow-up(p=0.026).Patients who received ABX had lower total relative abundance of their private bacterial strains during the maintenance period than those patients who had not received ABX suggesting enhanced engraftment with ABX (Mann-Whitney U test: p=0.018), although other comparisons between treatment groups did not show significant differences (figure 1b).Conclusion: Broad spectrum ABX may increase efficacy of FMT to achieve remission in patients with mild to moderate UC.Maintenance with FMT capsules in combination with pre-treatment antibiotic may be beneficial over enemas but larger, well-powered studies are required.