News from the AGA

Mixed results for fecal transplants in ulcerative colitis

Publish date: July 1, 2015
By
Bianca Nogrady
MDedge News

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Larger clinical trials needed

Though it has not yet been established whether dysbiosis is a cause or consequence of inflammation in inflammatory bowel disease, excitement among patients and clinicians around fecal microbiota transplantation in IBD has grown rapidly. Online success stories tout the “Power of Poop,” and patients don’t even need to wait for a new drug to come down the pipeline. For those ready to pursue FMT without hard efficacy and safety data, there are DIY guidebooks, YouTube videos, and websites to help them find donors.

Dr. Colleen R. Kelly

Both of these studies were underpowered, but they represent an improvement compared with previous case series and cohort studies, which were limited by small numbers of patients, open-label design, vague FMT protocols, incomplete reporting of IBD-specific data, and poorly defined outcomes. Neither showed FMT to be overwhelmingly beneficial, though there may have been signals of benefit in some subjects, in whom microbiome engraftment led to clinical remission and endoscopic response. Why was one study positive and the other negative, despite enrolling a similar patient population? Perhaps a lower GI route of administration and a more intensive dosing regimen are required to effectively alter the distal gut microbiome. Alternatively, there may be an optimal donor microbial profile. Anti-TNF agents may have impacted response through immunologic factors. Or were Moayeddi’s results only a statistical anomaly, driven by the unusually low 5% response in the placebo group?

What is clear is that these two studies are not game-changers. We have been manipulating the microbiome in IBD with antibiotics and probiotics for decades. Microbiota-based therapies may prove to be beneficial in some patients, but IBD is heterogeneous. If FMT can make some better, can it make others worse? Larger clinical trials to establish both efficacy and safety are critical before FMT can be considered ready for prime time.

Dr. Colleen Kelly is a gastroenterologist at the Women’s Medicine Collaborative and an assistant professor of medicine (clinical) at The Warren Alpert Medical School of Brown University, Providence, R.I. She is a consultant and site investigator for clinical trials at Seres Health, and has received research support from Assembly Biosciences.


 

References

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis (UC); 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the FMTs were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had UC for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor FMTs and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active UC were administered two transplants via nasoduodenal tube, 3 weeks apart, according to the paper published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.03.045).

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = .51), according to the intention-to-treat analysis.

In the per-protocol analysis, the difference between the active and control group was slightly greater but still did not reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor FMTs, but the study did find that, at 12 weeks, those who had received the donor FMTs and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies, and research funding from pharmaceutical companies. The second study was supported by MLDS and NWO-Spinoza, and no conflicts of interest were declared.

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