First-line treatment of fecal microbiota transplantation for immune-mediated colitis.
Authors: Varatharajalu Krishnavathana , Shatila Malek , Campbell Matthew T , Kovitz Craig A. , DuPont Herbert L. , Wang Yinghong 
Published: June 2024

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Background: The management of moderate to severe IMC includes immunosuppression with steroids and/or biologic agents. Long-term immunosuppression increases the risk for infections and steroid induced toxicities. Fecal microbiota transplantation (FMT) is increasingly used for the treatment of refractory IMC. Front-line FMT treatment has not been studied for IMC but could potentially alleviate IMC symptoms while reducing unnecessary extended exposure to steroids. In this study, we present a case series of 12 patients who received front-line FMT for the treatment of IMC as part of a clinical trial. Methods: This study reports preliminary data from a prospective clinical trial (NCT0403861) exploring the efficacy and safety of FMT as a first-line treatment for IMC. To be included, patients had to 1) have symptoms of immune-mediated diarrhea or colitis grade ≥ 2 (per Common Terminology Criteria for Adverse Events v5) within 45 days of FMT and 2) not have received any immunosuppressive treatment for IMC or any other indication around the time of FMT. Results: Twelve patients have been enrolled in the trial thus far. Patients received front-line FMT in a median of 31 days (IQR: 16-67 days) from IMC onset. 10 (83.3%) patients had symptom improvement in a median of 5 days (IQR: 1-7 days) after FMT. The only FMT-related adverse events reported were fatigue, transient fever, self-resolving abdominal cramping, and gassiness in six patients (50.0%) within the first week of FMT. One of the six patients additionally had recurrence of a previously existing frequent UTI due to bladder cancer within a week of FMT. Most patients (10, 83.3%) stopped immunotherapy due to IMC. Seven patients (63.6%) were able to resume cancer treatment after FMT, with four (33.3%) resuming checkpoint inhibitors. None of the patients that resumed ICI had recurrence of their colitis requiring immunosuppression. Nine patients (75%) had colitis remission by the end of the study period, with one additional patient showing signs of symptom improvement but passing away before his outcome could be assessed. Only two patients (16.7%) required immunosuppression for persistent colitis after FMT failure. Conclusions: This study is the first to evaluate the safety and efficacy of front-line FMT for the treatment of IMC. Our preliminary results are promising and show that FMT can be an effective first-line treatment for IMC that can quickly provide symptom relief in a majority of patients while avoiding the use of steroids. Our results also suggest that front-line FMT can be delivered in a timely manner and can allow for the safe resumption of immunotherapy in this population that typically responds well to immunotherapy. While more patients are needed before any solid conclusions may be drawn, there is mounting evidence to suggest that first-line FMT may be a safe and effective alternative to the current standard of care treatment for IMC. Clinical trial information: NCT04038619 .