Jessica R. Allegretti
SAN DIEGO — Results from the ICON study presented at DDW demonstrated that fecal microbiota transplantation was safe and effective in patients with inflammatory bowel disease and Clostridioides difficile infection.
“C. diff is a huge problem,” Jessica R. Allegretti, MD, director of the FMT program at Brigham and Women’s Hospital, said during her presentation. “It is the most common cause of health care associated infection in the U.S. still with an estimated half a million new cases annually.”
However, as Allegretti highlighted, the incidence is even higher in patients with inflammatory bowel disease.
“The scope of the problem in IBD patients is even more significant with a prevalence up to eightfold higher than their non-IBD cohorts,” she said. “These patients have a 10% lifetime risk contracting the infection and once they do have it, they have almost a fivefold higher risk of recurrent disease and we know that our patients with colitis are at the highest risk.”
Additionally, Allegretti noted, one of the biggest questions involved how to position fecal microbiota transplantation in the population.
“What we know is, there really is a lack of prospective data assessing these patients,” she said.
According to Allegretti, there have been three retrospective studies to date assessing the safety and efficacy of FMT for CDI in patients with IBD.
The CDI cure rates across those three studies were 79%, 85.7% and 97%.
Based on the lack of prospective data, Allegretti and colleagues aimed to assess the efficacy of FMT at eradicating CDI in patients with IBD-CDI and IBD clinical outcomes post-FMT.
The researchers conducted the open-label, multi-center trial across four sites in the U.S.
Patients were included in the ICON study if they had a confirmed recurrent CDI (two episodes or more) confirmed diagnosis of IBD with colonic involvement.
Patients underwent follow-up at weeks 1, 8 and 12 post-FMT and researchers collected blood samples and assessed clinical data such as diarrheal symptoms and IBD activity scores.
The efficacy of FMT at curing CDI in patients with IBD at week 8 served as the primary endpoint.
Secondary outcomes included adverse events related or possibly related to FMT, a de novo IBD flare (defined as a Mayo or HBI score 4 at week 12) and either worsening or improved IBD.
Thirty-seven patients (56.8% women; average age, 37.6 years; 37.8% Crohn’s disease; 62.2% ulcerative colitis) were included in the study and only three initially failed initial FMT but all were cured of CDI with an additional FMT.
Outcomes, as defined by the Harvey Bradshaw Index, either improved or there was no change in patients with CD. The same was true for ulcerative colitis outcomes defined by partial Mayo score, except for one de novo flare.
Allegretti did acknowledge that there were limitations to the study.
“This was an open-label study, so we don’t have a comparison arm, but we did feel it was an important first step in getting some prospective data in this really vulnerable patient population,” she said. “We unfortunately were not able to do follow-up colonoscopies to do a second mucosal assessment, but we were able to use fecal calprotectins as a surrogate for disease activity.”
Overall diversity improved after FTM and was sustained through 12 weeks and there were no significant microbial differences between patients who experienced a recurrence and those who did not.
“These data suggest that the efficacy and safety profile of FMT in IBD and C. diff is better than previously reported in retrospective studies,” Allegretti concluded. – by Ryan McDonald
Allegretti J, et al. Abstract 7. Presented at: Digestive Disease Week 2019. May 18-21; San Diego, California.
Disclosure: Allegretti reports she has ties to Finch Therapeutics, Janssen and Merck.