OP0256 EFFICACY OF FECAL MICROBIOTA TRANSPLANTATION ON FREQUENCY OF FECAL INCONTINENCE SYMPTOMS IN SYSTEMIC SCLEROSIS PATIENTS WITH MODERATE TO SEVERE LOWER GASTROINTESTINAL DISEASE
Authors: C. Nita, H. Fretheim, T. Garen, I. Barua, M. N. Carstens, H. Didriksen, V. K. Sarna, K. E. Lundin, O. Distler, D. Khanna, E. Volkmann, Ø. Midtvedt, T. Midtvedt, A. Dhainaut, A. K. H. Halse, G. Bakland, I. C. Olsen, M. E. Pesonen, Ø. Molberg, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The use of fecal microbiota transplantation (FMT) in systemic sclerosis (SSc) is an area of active investigation. The 20-week multicenter, randomized ReSScue trial [1] did not show efficacy of FMT by standard 'Anaerobic Cultivated Human Intestinal Microbiota' (ACHIM) on primary outcome (diarrhea or bloating), but the exploratory endpoint, impact of FMT on fecal incontinence (FI) symptoms, has not been assessed. <h3>Objectives:</h3> To evaluate the efficacy of FMT on FI in the randomized ReSScue trial. <h3>Methods:</h3> 67 SSc patients were randomly assigned to either placebo (n=34) or ACHIM treatment (n=33). The primary outcome and FI symptoms were assessed using the University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA GIT) at every visit. The Bristol Stool Form Scale assessed stool consistency at baseline and week 12. The impact of FI symptoms on quality of life was gauged using the Fecal Incontinence Quality of Life (FIQL) scale. One-way repeated measure analysis explored the behavior of FI symptoms over time. Changes meeting the minimally clinically important difference (MCID) threshold at week 20 were considered meaningful [2,3]. Effect size was calculated by Cohen's index (0.2 = small, 0.5 = moderate, 0.8 = large). Analyses were conducted for all patients, and a subset who reported FI at all time points (baseline, 12 and 20 weeks) and were defined as the "severe FI" cohort. <h3>Results:</h3> At baseline, 48 patients reported symptoms of FI with 24 in each treatment arm. The "severe FI" cohort included 14 patients, 8 in the ACHIM group and 6 in the placebo group. FMT-treated FI patients exhibited shorter disease duration and higher total UCLA GIT scores than placebo-FI patients (Table 1). At week 20, FMT-treated patients showed numerically improved UCLA fecal soilage scores, surpassing the MCID thresholds of "somewhat better" compared to the placebo group (Figure 1A,1C). Furthermore, the subset characterized by "severe FI" sustained improvement from 12 to 20 weeks (Figure 1B, 1C). Fewer FMT-treated patients reported loose stool at week 12, specifically 3 out of the initial 9 in the entire cohort and 6 in the "severe FI" cohort. In contrast, the placebo group had an additional two patients reporting watery stool. Over 20-weeks, despite reported changes in FI and stool consistency, patients did not perceive a corresponding improvement in their quality of life, consistently rating themselves as "about the same" on the FIQL scale. <h3>Conclusion:</h3> While the ReSScue trial showed no efficacy of FMT on bloating and diarrhea in SSc patients, the current analyses show that FMT significantly relieved FI symptoms, with consistent improvement over 20 weeks. A possible explanation might be the improved stool consistency leading to a decreased frequency of bowel loss. However, the positive results should be interpreted with caution given the wide 95% confidence intervals, limited number of participants, and short study duration. <h3>REFERENCES:</h3> [1] Hoffmann-Vold AM, Fretheim HH, Sarna VK, Barua I, Carstens MN, Distler O, et al. Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial. BMJ Open. 2021 Jun;11(6): e048541. [2] Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the university of california, los angeles scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis Rheum. 2009 Sep 15;61(9):1257–63. [3] 'T Hoen LA, Utomo E, Schouten WR, Blok BFM, Korfage IJ. The fecal incontinence quality of life scale (FIQL) and fecal incontinence severity index (FISI): Validation of the Dutch versions. Neurourology and Urodynamics. 2017 Mar;36(3):710–5. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Cristina Nita: None declared, Håvard Fretheim Boehringer Ingelheim, Bayer, Torhild Garen: None declared, Imon Barua: None declared, Maylen N Carstens: None declared, Henriette Didriksen: None declared, Vikas K. Sarna: None declared, Knut EA Lundin Takeda and Thermofisher, Takeda, Topas, Chugai, Alimentiv and GSK, Oliver Distler Boehringer Ingelheim, Janssen, Medscape, CITUS AG, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB, Dinesh Khanna: None declared, Elizabeth Volkmann Boehringer Ingelheim, GSK, Boehringer Ingelheim, Prometheus, Horizon, Øyvind Midtvedt: None declared, Tore Midtvedt: None declared, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge C. Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp &amp; Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp &amp; Dohme and Roche, Boehringer Ingelheim, Janssen.