From the Journals

Anaerobically prepared donor FMT led to steroid-free remission of ulcerative colitis

Publish date: January 15, 2019
By
Amy Karon

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Next step: Large multicenter trials

This is the fourth randomized clinical trial of fecal microbiota transplantation (FMT) in ulcerative colitis, and despite their differing methodologies, all four trials reported remission rates of 24%-32%, wrote Colleen R. Kelly, MD, and Ashwin N. Ananthakrishnan, MD, in an editorial accompanying the study.

Using pooled stool from multiple donors increases bacterial diversity and the likelihood that the sample will include a donor with optimal bacterial composition in the stool, the experts said. Based on studies to date, this approach works in about one-third of patients with ulcerative colitis, which resembles the rate of efficacy of systemic immunosuppression. Thus, FMT is likely to work best in combination with therapies such as immunomodulators and biologics, which target underlying immune dysregulation, they said.

Large multicenter trials are needed to answer questions on mechanism of action, optimal patient population and delivery methods, durability, and the use of FMT monotherapy versus combination regimens in patients with mild or severe ulcerative colitis, the experts wrote. “Finally, regulatory agencies must provide a reasonable pathway for approval of microbial-based therapeutics,” they added. “[The] therapeutic manipulation of the intestinal microbiota, whether by full-spectrum FMT or a more targeted approach using synthetic cultured consortia of bacterial species, is likely to be a component of therapy for [inflammatory bowel disease] and others in the not-so-distant future.”

Dr. Kelly is with Brown University in Providence, R.I. She disclosed ties to Finch Therapeutics and Openbiome. Dr. Ananthakrishnan is with Harvard Medical School, Boston. He disclosed ties to Pfizer and Gilead (JAMA. 2019;321[2]:151-2).


 

FROM JAMA

For patients with mild to moderate ulcerative colitis, a three-dose, 1-week induction course of anaerobically prepared donor fecal microbiota transplantation (FMT) produced steroid-free remission in 32% of patients, compared with 9% of those who received autologous aerobically prepared FMT in a randomized, double-blind, clinical trial.

Eight weeks after FMT, the odds of steroid-free remission were fivefold higher with anaerobically prepared donor versus aerobically prepared autologous FMT (odds ratio, 5; 95% confidence interval, 1.2-20.1; P = .03), reported Samuel P. Costello, MD, of the Queen Elizabeth Hospital in Woodville, Australia, and his associates. Donor FMT also significantly increased the likelihood of clinical remission and clinical response, the researchers said. “Further research is needed to assess longer-term maintenance of remission and safety,” they wrote in JAMA.

In prior studies, high-intensity FMT with aerobically prepared donor material remitted some cases of mild to moderate ulcerative colitis. However, anaerobic processing has been found to improve microbial viability, which might allow patients to remit with less intensive FMT, the researchers wrote. In their multicenter study, 73 adults with mildly to moderately active ulcerative colitis (total Mayo score, 3-10 points, with endoscopic subscore of at least 2) received either anaerobically prepared stool pooled from three to four highly screened donors or aerobically processed autologous stool. Patients in both arms received two enemas in the 7 days after FMT – a less dose-intensive treatment protocol than in prior FMT trials of patients with ulcerative colitis.

Among 38 patients in the intervention group, 12 (32%) achieved remission, defined as total Mayo score no greater than 2 with an endoscopic score no greater than 1. Strikingly, five (42%) of these patients remained in remission at 12 months, the researchers said. Additionally, 55% of the intervention group but only 23% of the comparator group (P = .007) achieved clinical response at 8 weeks, defined as at least a 3-point decrease in total Mayo score. Rates of clinical remission (Simple Colitis Activity Index score no greater than 2) were 47% and 17%, respectively (P = .01).

The study population averaged 39 years of age, 45% were women, and 95% completed the trial. Serious adverse events included one case each of worsening colitis, Clostridium difficile colitis requiring colectomy, and pneumonia in the donor FMT group, and two cases of worsening colitis in the comparator group. However, the study “was not powered to assess safety, and and thus further larger studies are required to assess this,” the researchers said. The study also suffered from a significant loss to follow-up at 12 months, so additional studies should assess long-term remission, they added.

The National Health and Medical Research Council and the Gutsy Foundation provided funding. Dr. Costello disclosed ties to Janssen, Shire, Ferring, Microbiotica, and Pfizer.

SOURCE: Costello SP et al. JAMA. 2019;321(2):156-64. doi: 10.1001/jama.2018.20046.

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