Fecal microbiota transplantation (FMT) appears safe and effective for treating recurrent Clostridioides difficile infection in patients with inflammatory bowel disease (IBD), according to an ongoing prospective trial.
Most patients were cured of C. difficile after one fecal transplant, reported Jessica Allegretti, MD, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.
“[For patients without IBD], fecal microbiota transplantation has been shown to be very effective for the treatment of recurrent C. diff,” Dr. Allegretti said at the annual Gut Microbiota for Health World Summit.
But similar data for patients with IBD are scarce, and this knowledge gap has high clinical relevance, Dr. Allegretti said. She noted that C. difficile infections are eight times more common among patients with IBD, and risk of recurrence is increased 4.5-fold.
According to Dr. Allegretti, three small clinical trials have tested FMT for treating recurrent C. difficile infections in patients with IBD.
“[These studies were] somewhat prospective, but [data] mainly retrospectively collected, as they relied heavily on chart review for the assessment of IBD disease activity,” she said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility..
Across the trials, C. difficile infection cure rates were comparable with non-IBD cohorts; but disease flare rates ranged from 17.9% to 54%, which raised concern that FMT may trigger inflammation.
To investigate further, Dr. Allegretti and her colleagues designed a prospective trial that is set to enroll 50 patients with IBD. Among 37 patients treated to date, a slight majority were women (56.8%), about one-third had Crohn’s disease (37.8%), and two-thirds had ulcerative colitis (62.2%). The average baseline calprotectin level, which measures inflammation in the intestines, was 1,804.8 microg/g of feces, which is far above the upper limit of 50 microg/g.
“This is a very inflamed patient population,” Dr. Allegretti said.
Out of these 37 patients, 34 (92%) were cured of C. difficile infection after only one fecal transplant, and the remaining three patients were cured after a second FMT.
“They all did very well,” Dr. Allegretti said.
Concerning IBD clinical scores, all patients with Crohn’s disease either had unchanged or improved disease. Among those with ulcerative colitis, almost all had unchanged or improved disease, except for one patient who had a de novo flare.
Early microbiome analyses showed patients had increased alpha diversity and richness after FMT that was sustained through week 12. Because only three patients had recurrence, numbers were too small to generate predictive data based on relative abundance.
Dr. Allegretti continued her presentation with a review of FMT for IBD in general.
“For Crohn’s disease, the role [of microbiome manipulation] seems a bit more clear,” Dr. Allegretti said, considering multiple effective treatments that alter gut flora, such as antibiotics.
In contrast, the role for microbiome manipulation in treating ulcerative colitis “has remained a bit unclear,” she said. Although some probiotics appear effective for treating mild disease, other microbiome-altering treatments, such as diversion of fecal stream, antibiotics, and bowel rest, have fallen short.
Still, pooled data from four randomized clinical trials showed that FMT led to remission in 28% of patients with ulcerative colitis, compared with 9% who receive placebo.
“You may be thinking that seems a bit underwhelming compared to the 90% or so cure rate we get for C. diff trials,” Dr. Allegretti said. “However, if you look at our other biologic trials in IBD, 28% puts FMT on par with our other IBD therapies.”
According to Dr. Allegretti, at least three stool-based, FMT-like therapeutics are poised to become commercially available in the next few years for the treatment of C. difficile infection, including broad- and narrow-spectrum enema bags and oral capsules.
“I certainly think we will start to see off-label usage in our IBD patients, and we will start to have an easier and more systemic way of utilizing these microbiome-based therapies,” Dr. Allegretti said. “They will be coming to market, and when they do, whether or not we are allowed to still do traditional FMT in its current form remains unseen. The FDA may not allow us to do that in the future when we have an FDA-approved product.”Dr. Allegretti disclosed relationships with Merck, Openbiome, Finch Therapeutics, and others.
