19 May 2021
FMT falls flat in first PsA trial
A small Danish study finds stool transplants are generally safe but it remains to be seen whether FMT is effective for treating active psoriatic arthritis.
The proof-of-concept study was the first randomised placebo-controlled trial to test the safety and efficacy of faecal microbiota transplantation (FMT) as a treatment of immune-related arthritis.
The Danish trial, published in Annals of Rheumatic Disease, randomised 31 patients with active PsA on methotrexate to receive either one gastroscopic-guided, single-donor FMT or a sham transplant.
No serious adverse events were reported in the 26-week trial, which had a primary focus on safety, and adverse events were mostly gastrointestinal, such as nausea, vomiting and flatulence. But the trial was neither large enough nor long enough to evaluate uncommon side effects and long-term risks, the study authors noted.
More patients in the FMT group needed additional treatments for their PsA symptoms compared to the control group, who had better physical function measured by HAQ-DI.
“While previous case reports have shown the potential of FMT, this study finds no evidence of treatment success and suggests FMT may worsen symptoms in some patients,” said Dr Sam Forster, a microbiome and bacteriotherapy researcher at the Hudson Institute of Medical Research in Melbourne, who was not involved in the study.
One such case report, from the Queen Elizabeth Hospital in South Australia, detailed the case of a woman with PsA who reported a dramatic improvement in joint symptoms and reduced disease activity for at least 10 months after receiving a stool transplant for a Clostridioides difficile infection.
Although there is sound clinical evidence that FMT is an effective treatment for recurrent C. diff infections, it has been less effective for treating more complex conditions such as inflammatory bowel disease.
However, it still remains an attractive treatment strategy for rheumatic diseases, and the study authors noted that the presence of an effect – even though negative – added evidence for the suggestion that intestinal microbiota play a role in the immune effects of PsA.
Despite the results, a small group of trial participants who were involved in a parallel study (published in BMJ Open) to document their perceptions of FMT, said they maintained a strong belief in its therapeutic potential. They also deemed FMT to be acceptable and safe at the end of the trial, after initial concerns, and were supportive of more research.
Dr Forster told Rheumatology Republic that the trial has provided important first insights into FMT as a possible treatment for arthritis. However, he noted some flaws regarding treatment preparation in the study that may have affected sample viability.
Stool samples need to be protected from oxygen exposure, Dr Forster said, and multiple treatments may also be required to appropriately disrupt a person’s existing bacterial community in complex conditions such as arthritis.
He said research into FMT is in its very early stages and holds “enormous potential” for treating inflammatory disease but requires further investigation to examine its therapeutic benefit for specific conditions and to refine transplant protocols.
“This study provides initial evidence for safety but further work will be required to determine if, with the right pre-treatments and selection of appropriately matched donors, FMT has potential for the treatment of arthritis,” Dr Forster said.