Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial

Abstract

ObjectivesAlthough causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).MethodsIn this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.ResultsOf 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).ConclusionsIn this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.Trial registration numberNCT03058900.

Response to: ‘Correspondence on ‘Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial’’ by McGonagleet al

“…We thank McGonagle et al 1 for their insightful comments on our manuscript on faecal microbiota transplantation (FMT) in active peripheral psoriatic arthritis (PsA), known as the FLORA trial. 2 We agree that the clinical findings of this first doubleblind, randomised, trial of FMT in immune-mediated arthritis warrant further investigation into the underlying biological mechanisms coupling gut composition, the intestinal barriermicrobiotal interaction, and systemic inflammation in PsA and related chronic inflammatory diseases. Indeed, evidence linking the composition of the gut microbiota and initiation/progression of immune-mediated disease is limited and is primarily derived from animal models.…”

Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response

“…However, a recent experiment seems to disagree. This is a double-blind, parallelgroup, placebo-controlled, superiority trial (141), showing that FMT from selected donors can worsen psoriatic arthritis (PsA) symptoms. The failure rate (i.e., patients requiring intensive treatment) was significantly higher in the FMT group than in the control group.…”

“…The failure rate (i.e., patients requiring intensive treatment) was significantly higher in the FMT group than in the control group. Therefore, other mechanisms, such as the degree and persistence of donor microbiota implantation, and some external factors related to FMT, such as aerobic and anaerobic environment (141), need to be further attended in the future.…”

Correspondence on ‘Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial’

“…5 Kragsnaes et al employed the Spondyloarthritis Research Consortium of Canada (SPARCC) index where a mean 4.3 unit improvement was noted in the FMT sham group versus 1.9 units in the FMT group. 1 This raises the novel concept that FMT might be transiently disturbing the intestinal homeostasis and favours a flare in disease before later restoration of immune homeostasis, although this was not studied in their report.…”

“…We read with great interest the report by Kragsnaes et al on faecal microbiota transplantation (FMT) in active psoriatic arthritis (PsA). 1 The authors cited the example of reactive arthritis (ReA) as an exemplar of how dysregulation of the intestinal microbiome may contribute to the immunopathogenesis of human arthritis by disturbance of the gut-joint axis. We appreciate that limitations in word count may have constrained Kragsnaes et al on commenting further on gut dysbiosis in arthritis.…”