Jessica R. Allegretti, MD, MPH1, Colleen Kelly, MD, FACG2, Ari M. Grinspan, MD3, Benjamin H. Mullish, MBBChir, PhD4, Jonathan Hurtado, BA1, Sara Nemes, BA5, Sashidhar Sagi, MD6, Matthew Bohm, DO6, Zain Kassam, MD, MPH7, Monika Fischer, MD, MSc6; 1Brigham & Women's Hospital, Boston, MA; 2Warren Alpert Medical School of Brown University, Providence, RI; 3Mount Sinai Hospital, New York, NY; 4Imperial College London, London, England, United Kingdom; 5Indiana University, Indianapolis, IN; 6Indiana University School of Medicine, Indianapolis, IN; 7Finch Therapeutics, Somerville, MA
Introduction: Patients with inflammatory bowel disease (IBD) are at increased risk for C. difficile infection (CDI) and associated morbidity and mortality. Persistent C. difficile colonization occurs even after standard-of-care CDI antibiotics, and may contribute to the increased risk of recurrent CDI. Additionally, C. difficile colonization has public health consequences as patients may spread C. difficile and may lead to contact isolation and high-cost cleaning procedures in a healthcare setting. Fecal microbiota transplantation (FMT) is a promising therapy for recurrent CDI, however its efficacy among IBD patients is limited and the rate of decolonization is unknown. Accordingly, we assessed the safety, efficacy and C. difficile decolonization rate in in IBD patients with recurrent CDI following FMT. Methods: This open-label, prospective single-arm multicenter cohort study enrolled patients from 4 tertiary care centers. Patients with IBD and 2 or more episodes of CDI received a single colonoscopic FMT from a universal stool bank. CDI testing (GDH/Toxin EIA and PCR) was performed pre-FMT, and at 1, 8, and 12 weeks post-FMT. The primary outcome was FMT failure through week 8 (defined as diarrhea and Toxin EIA positive for C. difficile). The secondary outcome assessed was C. difficile decolonization post-FMT (defined as negative PCR testing) at week 12. Results: 50 participants were enrolled with a mean age of 43.3 years (range 21-91) and primarily female (n=28, 56%), 14 of which had Crohn’s disease (CD) (mean HBI=6.4) and 36 had ulcerative colitis (UC) (mean Partial Mayo Score=4.5). One patient did not receive FMT after enrollment. There were no treatment-related serious adverse events. Among the treated patients, 8% (4/49) participants experienced a confirmed FMT failure and received a second FMT. Two additional patients received a repeat FMT based on investigator discretion. In terms of C. difficile decolonization, 88.9% (40/45 eligible participants) experienced decolonization at week 12 follow-up period. Discussion: To our knowledge, this is the largest prospective trial to assess the safety, efficacy and C. difficile decolonization rate of FMT in patients with IBD-CDI. This data suggests FMT is a safe and promising therapy for preventing CDI recurrence and achieving C. difficile decolonization which may have public health and economic implications. Future randomized controlled trials are needed.
Disclosures: Jessica Allegretti: Finch Therapeutics – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Merck – Grant/Research Support. Pandion – Consultant. Pfizer – Consultant. Servatus – Consultant. Takeda – Consultant. Colleen Kelly: Finch Therapeutics – Grant/Research Support. Ari Grinspan indicated no relevant financial relationships. Benjamin Mullish: Finch Therapeutics Group – Consultant. Jonathan Hurtado indicated no relevant financial relationships. Sara Nemes indicated no relevant financial relationships. Sashidhar Sagi indicated no relevant financial relationships. Matthew Bohm indicated no relevant financial relationships. Zain Kassam: Finch Therapeutics – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Monika Fischer: Finch Therapeutics – Consultant, Grant/Research Support.