FMT workshop covers recent advances, regulations, future therapies

Monika Fischer

LAS VEGAS — In this exclusive guest commentary, Monika Fischer, MD, associate professor of medicine in the division of gastroenterology and hepatology at Indiana University School of Medicine, discusses the workshop on fecal microbiota transplantation (FMT) held at the Crohn’s & Colitis Congress, which covered the current state of the science, regulations, and future therapeutics.

I participated in the AGA’s fecal transplant workshop for the clinician. We learned during this workshop that testing for Clostridium difficile is quite controversial, and the polymerase chain reaction (PCR) used at most centers is over-sensitive, thus we probably over-diagnose C. difficile. The current recommendation now includes toxin testing, or two-step testing, which is more likely to identify patients who have a clinically relevant C. diff infection vs. those colonized with C. diff. New European guidelines recommend that testing should either include a PCR-based or a glutamate dehydrogenase (GDH)-based initial step, and if that’s positive, then toxin testing by ELISA.

We also learned about new formulations for fecal transplant, including frozen capsules. A recent study by Dina Kao, MD, of University of Alberta, and colleagues, published in JAMA showed a 96% success rate with 40 capsules using frozen fecal transplant, and the success rate was equivalent to the success rate achieved by FMT via colonoscopy. Alexander Khoruts, MD, of the University of Minnesota, and colleagues also published data on a new formulation with freeze-dried capsules, and his group was able to achieve nearly 90% success with only giving two to three capsules of freeze-dried fecal microbiota without any bowel preparation.

Further talks concerned how to manage FMT non-responders. To confirm the diagnosis of FMT failures, we must ensure that these patients actually have C. diff and do not have an alternative diagnosis that actually causes their diarrhea, such as underlying inflammatory bowel disease, celiac disease, or usual mimics of C. diff. Our current recommendation is, after confirming the failure, to repeat the fecal transplant at least two or three more times, if the patient is willing, preferably going the colonoscopy route if the first two FMTs were administered via a different route. One could also consider alternative therapies such as Zinplava (bezlotoxumab, Merck), repeating vancomycin or using fidaxomicin for at least a month.

We also discussed that for patients who are elderly and frail or at the end of their life, we could consider low-dose suppressive vancomycin therapy and not fecal transplant.

Additionally, we talked about the potential role of fecal transplant in other diseases, including IBD. The studies are promising for ulcerative colitis. We had a speaker, Max Nieuwdorp, MD, PhD, of the University of Amsterdam, who performed pioneering work in using fecal transplant in metabolic syndrome or insulin resistance. There are possibilities for treatment of autism, and even depression with fecal transplant.

Finally, we discussed whether regulatory oversight is necessary, whether it would help the patients by improving safety, or if it might even hamper the process, because it would prohibit the physicians from providing fecal transplant or make the logistics of fecal transplant more complicated. That was a very interesting discussion. There were pros and cons to the argument and we could not reach a consensus. The FDA currently allows physicians to use fecal transplant but only for the indication of therapy refractory C. diff.

I found this workshop to be very useful and I recommend that my peers look up the details if they are interested in the latest developments in FMT.

Reference:

A Clinician’s Guide to Fecal Microbiota Transplant (FMT). Presented at: Crohn’s & Colitis Congress; Jan. 19-20, 2018; Las Vegas, NV.

Disclosures: Fischer reports she is a research consultant for OpenBiome and Finch Therapeutics.