Of the 89 volunteers who received the treatment, known as SER-109, 12% had a C. difficile recurrence versus 40% of the 93 patients who received 12 placebo capsules over 3 days (P<0.001).
Side effects, most of which were gastrointestinal, were seen in 88% of spore recipients and 87% of placebo patients. Most of the adverse events were ranked as mild or moderate.
The test, known as ECOSPOR III, was financed by Seres Therapeutics.
"The results are incredibly exciting," chief author Dr. Paul Feuerstadt of the Yale University School of Medicine in New Haven, Connecticut, told Reuters Health in a telephone interview.
The therapy has the potential to make "a massive difference in patients' lives," he said. "The patients that go through recurrent and multiply-recurrent C. difficile infections live with PTSD (post-traumatic stress disorder) worrying that this is going to come back. To have a treatment like this that can really shut this down is huge."
C. difficile and the toxin it produces kill about 20,000 people in the United States each year and make 460,000 people ill with colonic inflammation and debilitating diarrhea. Antibiotic therapy can leave behind C. difficile spores that can cause a recurrence. Other microbes in the gut can keep the disease from taking over, but too many of those healthy microbes can be killed when antibiotic therapy is given for other reasons.
Transplants of fecal material have shown some promise in restoring intestinal health and the SER-109 treatment is designed to restore the balance using beneficial Firmicutes bacteria, without the risk that a pathogen might be inadvertently introduced, as might happen in a transplant.
The treatments were done at 56 centers in the United States and Canada. All the adults had experienced at least three episodes of C. difficile infection during the previous year. The spores used in the treatment were collected and purified from four heavily-screened individuals.
"Within a week, these spores have taken hold and that's why the response rate is so good," said Dr. Feuerstadt, an assistant clinical professor of medicine at Yale and a gastroenterologist at PACT Gastroenterology Center in Hamden, Connecticut.
The Journal study only covers patients eight weeks after treatment, but "the sustained effects were excellent and remained out to about six months," he said. "The majority that responded initially had a sustained clinical response."
At 8 weeks, the treatment seemed slightly more effective in patients under 65. The younger group saw a 76% reduction in recurrence. Symptoms reappeared in 7% of spore recipients compared with 31% of placebo patients.
Among volunteers aged 65 and older, the recurrence rate was 17% with the experimental treatment versus 46% with placebo, a 64% reduction.
The recurrence rate after 8 weeks was also lower among patients initially treated with fidaxomicin compared with vancomycin.
In the fidaxomicin group, the recurrence rate was only 4% with SER-109 therapy compared with 46% with placebo, a 91% reduction. With vancomycin therapy, the respective rates were 16% and 38%, a 59% reduction.
"Most recurrence events occurred rapidly, with onset as early as day 4 after randomization," the researchers reported. "Of the 48 recurrences that occurred in the overall trial population by week 8, a total of 36 (75%) occurred within 2 weeks and 41 (85%) occurred within 4 weeks after administration of SER-109 or placebo."
There were three deaths among the 89 in the treatment group, but the researchers ruled that none were related to the therapy. The causes of death were glioblastoma progression, subdural hematoma after a fall, and recurrent tachycardia with hypotension in a patient with a history of heart problems.
Among other side effects reported in the seven days after treatment completion, gastrointestinal disorders were the most common, occurring in 88% of spore-treated patients and 87% among placebo patients.
Side effects where the rate was at least 5 percentage points higher among SER-109 recipients included constipation (seen in 31% of the treatment group) and urinary tract infections (7%)
Side effects where the rate was at least 5 percentage points higher among placebo recipients included flatulence (seen in 70% of the treatment group), abdominal pain (51%), nausea (18%), vomiting (3%) decreased appetite (29%) and C. difficile colitis (1%).
"The side effect profile was truly minimal," Dr. Feuerstadt said.
SOURCE: https://bit.ly/33ym8MD The New England Journal of Medicine, online January 19, 2022.
By Gene Emery
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