Fecal microbiota transplantation (FMT) showed disappointing results among patients with active psoriatic arthritis, a small randomized trial found.
During 26 weeks of follow-up, the risk of treatment failure was higher among patients receiving FMT compared with those given a sham treatment, with a hazard ratio of 4.87 (95% CI 1.31-18.18, P=0.018), according to Torkell Ellingsen, MD, of Odense University Hospital in Denmark, and colleagues.
And by the end of the 26 weeks of observation, treatment failure had occurred more frequently among patients in the FMT group than among those receiving the sham transplant (60% vs 19%), for a crude relative risk of 3.20 (95% CI 1.06-9.62, P=0.018), the researchers reported in Annals of the Rheumatic Diseases.
“For a century, the link between enteric infections and reactive arthritis has motivated investigation into the proposed gut-joint axis implicating intestinal micro-organisms in the etiology of immune-mediated arthritic disease,” the team wrote.
Interest has further grown with the increased understanding of intestinal dysbiosis and disease, the investigators noted. Lower bacterial diversity and abnormal microbial patterns have been reported in inflammatory bowel disease, rheumatoid arthritis, and psoriatic arthritis.
“These findings have encouraged research into the host-microbiota interplay in the dysregulated immunological cascade underlying immune-mediated arthritis and the prospects of microbiota-targeted therapies,” Ellingsen and co-authors stated.
While success has been seen with FMT for inflammatory bowel disease, it has not been determined whether extraintestinal immune-mediated disease could be influenced by this approach.
Accordingly, the researchers conducted a proof-of-concept single-center study that included 31 patients with active polyarthritic psoriatic arthritis despite treatment with methotrexate given in dosages of 15 mg/week or higher.
The transplant material was obtained from four healthy donors, and was placed in the third part of the duodenum in doses of 50 g.
The primary endpoint of treatment failure was defined as the need for more than one intra-articular steroid injection or the need for intensified treatment with conventional or biologic antirheumatic agents. Additional secondary endpoints included the change at week 26 in the Health Assessment Questionnaire Disability Index (HAQ-DI) and the number of patients with a 20% improvement on the criteria of the American College of Rheumatology (ACR20).
The two groups were largely similar, with two-thirds being women and a mean age of 51. Disease duration was almost 4 years.
Baseline HAQ-DI was 0.83, and tender and swollen joint counts averaged 16.1 and 7.1, respectively.
By week 12, 53% of patients in the FMT group had started treatment with a biologic compared with 13% of those in the sham group, and the median time to starting biologic treatment was 32 days in the FMT group compared with 99 days in the sham group.
Change in HAQ-DI, representing improved physical function, was greater in the sham group, at -0.30 (95% CI -0.44 to -0.15) than in the FMT group, at -0.07 (95% CI -0.22 to 0.09).
No difference in the rate of ACR20 responses was seen between the FMT and sham groups (47% vs 50%, RR 0.93, 95% CI 0.45-1.94).
The treatment did appear to be safe, with no serious adverse events or deaths occurring in either group, the researchers reported. Most events were gastrointestinal, such as nausea, vomiting, and flatulence.
“Treatment failure occurred very quickly after the procedure in patients receiving FMT. Because of the comparable disease activity between groups at baseline, our findings suggest that FMT from selected donors can worsen the symptoms of psoriatic arthritis,” the investigators noted.
Factors that could have contributed to the high failure rate in the FMT group included the possibility that non-inflammatory factors such as structural damage may have influenced patients’ and providers’ decision to initiate biologic therapy, and the fact that patients had active disease and multiple affected joints.
A limitation of the study, the team said, was the small number of patients included: Larger studies will be needed to further explore the concept of the gut-joint axis in psoriatic arthritis, and such trials should include more participants “combined with exploration of immunological effects and in-depth analyses of the composition and functional potential of the microbiota in donor and recipients,” Ellingsen and co-authors noted.
The study was funded by the Danish Rheumatism Association, the Danish Psoriasis Research Foundation, the University of Southern Denmark Research Fund, the Research Fund of Odense University Hospital, the Danish Regions, the Region of Southern Denmark Research Fund, and Novartis Healthcare.
Ellingsen reported no disclosures; co-authors reported financial relationships with Merck, Janssen, the Oak Foundation, Pfizer, Celgene, Orkla Health, Mundipharma, Novartis, Biogen, and Eli Lilly.