Background:Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel therapeutic option for treatment of extra-intestinal inflammatory diseases.¹Objectives:In this proof-of-concept study, we evaluated efficacy and safety of FMT in psoriatic arthritis (PsA).²Methods:In this double-blind, parallel-group, sham-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. The transplants (50 g faeces) came from one of four healthy, thoroughly screened, anonymous stool donors.3 The primary efficacy endpoint was the proportion of participants experiencing treatment failure (i.e., needing treatment intensification) through 26 weeks. The first key secondary endpoint was change in Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to week 26. Safety was monitored throughout the trial. Trial registration number: NCT03058900, ClinicalTrials.gov.Results:Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT), all received the assigned intervention, and 30 (97%) completed the 26-week clinical evaluation (Table 1). 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). During the entire 26 weeks of observation, the rate of the treatment failures was significantly higher in the FMT than in the sham group, see figure 1. Improvement in HAQ-DI score 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. No serious adverse events were observed.Conclusion:In this first interventional randomised controlled trial of FMT in immune-mediated arthritis, FMT was inferior to sham in treating active peripheral PsA. FMT did not appear to result in serious adverse events.Figure 1.Time-to-event curves by intervention group from baseline to week 26. FMT, faecal microbiota transplantation.Table 1.Baseline demographics and disease characteristics.CharacteristicFMT(n=15)Sham(n=16)Female sex, no. (%)8 (53%)12 (75%)Age, yr.48.9 (16.1)52.4 (11.0)Height, cm175.2 (7.0)169.8 (8.6)Weight, kg93.6 (15.4)92.4 (24.8)Time since diagnosis, yr.^a2.6 (0.3 to 5.8)5.6 (0.5 to 8.8)Rheumatoid factor IgM negative, no. (%)^b13 (93%)15 (94%)Anti-citrullinated peptide antibody negative, no. (%)^b14 (100%)16 (100%)HLA-B27 negative, no. (%)15 (100%)13 (81%)C-reactive protein, mg/L4.98 (7.18)5.54 (5.87)HAQ-DI0.89 (0.51)0.78 (0.50)Swollen joint 66 count7.5 (3.0)6.7 (2.7)Tender joint 68 count14.9 (8.9)17.3 (8.8)SPARCC enthesitis index Score ≥1, no. (%)13 (87%)15 (94%) Score in patients with a score ≥18.1 (4.3)7.2 (3.3)Data are mean (SD) or n (%) unless otherwise stated. FMT, faecal microbiota transplantation. ^a Time since diagnosis of psoriatic arthritis is presented as median and interquartile range (IQR). ^b Presence of rheumatoid factor (IgM) and anti-citrullinated peptide antibody was not accessed in one patient from the FMT group.References:[1]Manasson J, Blank RB, Scher JU. The microbiome in rheumatology: Where are we and where should we go? Ann Rheum Dis 2020;79:727-33.[2]Kragsnaes MS, Kjeldsen J, Horn HC, et al. Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial. BMJ Open 2018;8:e019231.[3]Kragsnaes MS, Nilsson AC, Kjeldsen J, et al. How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service? Transfusion 2020;60:1135-41.Acknowledgements:We thank all participants for their contribution. We thank CS Klinkby, trial nurse, for assistance in relation to the conduct of the trial visits. We also thank L Albjerg, biomedical laboratory technologist, AC Nilsson, consultant, KF Rasmussen, consultant, and J Georgsen, consultant, at the Department of Clinical Immunology, Odense University Hospital, Denmark, for assisting in the implementation of the FMT stool bank.Disclosure of Interests:Maja Skov Kragsnaes Grant/research support from: Novartis 2017 (unrestricted research grant) to support 3 months PhD salary related to the conduct of the trial., Jens Kjeldsen: None declared, Hans Christian Horn: None declared, Heidi Lausten Munk: None declared, Jens Kristian Pedersen: None declared, Søren Andreas Just: None declared, Palle Ahlquist: None declared, Finn Moeller Pedersen: None declared, Maarten de Wit: None declared, Sören Möller: None declared, Vibeke Andersen: None declared, Karsten Kristiansen: None declared, Hanne Marie Holt: None declared, Dorte Kinggaard Holm: None declared, Robin Christensen: None declared, Torkell Ellingsen Grant/research support from: Novartis 2017 (unrestricted research grant)