Orally administered fecal microbiota transplantation (FMT) following use of antibiotics was associated with induction of remission in patients with active ulcerative colitis, according to a study in the Lancet Gastroenterology & Hepatology.
The Lyophilized Oral Fecal Microbiota Transplantation in Ulcerative Colitis (LOTUS) study evaluated the efficacy and safety of pretreatment antibiotics followed by oral lyophilized FMT derived from selected donors for treatment of patients with active ulcerative colitis.
The randomized, double-blind, placebo-controlled trial was conducted in Sydney, Australia, and included patients aged 18 to 75 years with a diagnosis of ulcerative colitis for more than 3 months. All patients had clinical and endoscopic active ulcerative colitis.
Participants received a 2-week course of oral pre-FMT antibiotics that included amoxicillin hyclate 500 mg 3 times daily, doxycycline hyclate 100 mg twice daily, and metronidazole hyclate 400 mg twice daily. The patients were then randomly assigned to receive either FMT or placebo.
The primary outcome at week 8 was the combination of corticosteroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2, with all Mayo subscores ≤1, and a ≥1-point reduction in Mayo endoscopic subscore from baseline endoscopy). FMT responders at week 8 were randomly assigned (1:1 ratio, permuted block size of 8) to continue or withdraw FMT for an additional 48 weeks.
A total of 35 patients were assigned randomly to FMT (n=15; median age, 37.1 years; 60% men) or placebo (n=20; median age, 36.7 years; 55% women) from May 20, 2019, to March 24, 2020. In the FMT group, 3 patients (20%) discontinued treatment or had protocol failure before week 8 compared with 5 patients (25%) in the placebo group.
At week 8, 8 patients (53%) in the FMT group and 3 (15%) in the placebo group were in corticosteroid-free clinical remission and either endoscopic remission or response (difference 38.3%; 95% CI, 8.6-68.0; P =.027; odds ratio [OR] 5.0; 95% CI, 1.8-14.1).
Regarding adverse events, 10 patients (67%) in the FMT group and 17 (85%) in the placebo group had at least 1 event in the 8-week induction period, with self-limiting gastrointestinal complaints the most common.
A total of 4 serious adverse events occurred in the blinded study period — 2 in each the FMT and placebo groups. Worsening of ulcerative colitis with objective increased inflammatory activity that required treatment escalation occurred in 2 patients in the FMT group and in 1 patient in the placebo group.
In further analysis, 10 patients in the FMT group who had a clinical or endoscopic response entered the maintenance withdrawal study and were randomly allocated to continue open-label FMT (n=4) or withdraw therapy (n=6). Among those who continued FMT, all 4 patients were in clinical, endoscopic, and histologic remission at week 56 vs none of those in the FMT withdrawal group.
Study limitations included the inability to complete recruitment due to the SARS-CoV-2 pandemic, as well as the limited number of patients who entered into the maintenance phase. Additionally, use of pre-FMT antibiotics was not randomized.
“Our study showed that an all-oral regimen of FMT is a promising therapy for the induction and subsequent maintenance of remission in patients with ulcerative colitis, and builds upon the existing literature surrounding microbial manipulation therapy,” the investigators stated.
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Haifer C, Paramsothy S, Kaakoush NO, et al. Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2022;7(2):141-151. doi: 10.1016/S2468-1253(21)00400-3