FMT Appears Ineffective for Treatment of IBD

Issue: February 2015

ORLANDO, Fla. — Mounting evidence shows that while fecal microbiota transplant appears to be a highly effective therapy for Clostridium difficile infection, it does not appear to be efficacious for treating inflammatory bowel disease, according to a presenter here.

In his presentation, Edward V. Loftus, MD, FACG, AGAF, from Mayo Clinic in Rochester, Minn., demonstrated that data on fecal microbiota transplant (FMT) for C. diff infection (CDI) is well established. A 2013 systematic review and meta-analysis of 11 studies including 273 patients with CDI demonstrated a pooled resolution rate of 89%, and in a randomized trial of FMT vs. vancomycin for CDI, he said, “the patients who were receiving the fecal transplant were doing so well that they terminated the study early.

Edward V. Loftus

“So we have clear cut evidence that FMT works for recurrent C. diff,” Loftus said. “But what about FMT for IBD?”

Early data was “encouraging,” he said. A 2012 systematic review and meta-analysis, for example, showed that 13 out of 17 patients who received FMT for IBD were able to stop IBD medication within 6 weeks, 16 patients had symptom reduction or resolution within 4 months. Of 24 patients, 63% had no evidence of active disease 3 to 36 months after FMT.

Loftus warned, however, “now that we are seeing more rigorous studies, we are not seeing quite the same effect.” A recent systematic review and meta-analysis of 18 studies, including 122 patients, showed an overall response rate of 45% (22% UC, 61% Crohn’s disease), demonstrating that FMT for IBD is safe, but the effectiveness is highly variable, he said.

An additional systematic review of 31 studies of 133 patients showed resolution or reduction of symptoms in 71%, but that dropped to 62% when an objective score was used, and similarly the endoscopic improvement rate of 57% dropped to 20% when an objective score was used.

“So as more objectivity and reality is being infused into this area, the results are not nearly as glowing as they were initially described,” Loftus said.

Punctuating this point were results from a randomized control trial of 53 UC patients that demonstrated no difference in remission between FMT and placebo at week 6 (IBDQ, P=.82; Mayo Score, P=.52). “This study has been criticized by some because of the small sample size and short duration, but there’s not even a signal of a benefit in this study,” he said.

When it comes to IBD patients with CDI, however, “the theme seems to be that it works for eradicating the recurrent C. diff but is maybe not effective for treating the IBD,” Loftus said.

In a multicenter retrospective analysis of 80 CDI patients, for example, the 36 patients with IBD had a 94% overall CDI cure rate with a serious adverse event rate similar to those without IBD (11%), but 14% had a disease flare after FMT. Another study from the Mayo Clinic demonstrated 92% clinical improvement after FMT for the treatment of CDI in patients with IBD, “however none of these patients stopped their IBD therapies,” Loftus said. “In fact 46% of them required escalation of their IBD therapy at some point in follow-up.

“FMT does appear to be highly effective in eradicating recurrent C. diff. In the subset of IBD patients with recurrent C. diff it also appears to be highly effective and reasonably safe, including patients on immunomodulators and biologics. But it is far from certain that FMT itself will be effective for treatment of IBD in the absence of recurrent C. diff, and I think we need additional placebo controlled trial to answer this. The one placebo controlled trial that we do have right now has been negative.” – by Adam Leitenberger

For more information:

Loftus EV. Presented at: 2014 Advances in Inflammatory Bowel Diseases, Dec. 4-6; Orlando, Fla.

Disclosure: Loftus reports numerous financial disclosures.