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Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial
  1. Maja Skov Kragsnaes1,2,
  2. Jens Kjeldsen3,
  3. Hans Christian Horn1,
  4. Heidi Lausten Munk1,
  5. Jens Kristian Pedersen4,
  6. Søren Andreas Just4,
  7. Palle Ahlquist5,
  8. Finn Moeller Pedersen3,
  9. Maarten de Wit6,
  10. Sören Möller2,7,
  11. Vibeke Andersen8,9,
  12. Karsten Kristiansen10,11,
  13. Dorte Kinggaard Holm12,
  14. Hanne Marie Holt13,
  15. Robin Christensen2,14,
  16. Torkell Ellingsen1,2
  1. 1Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital, Odense, Denmark
  2. 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  3. 3Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
  4. 4Section of Rheumatology, Department of Medicine, Svendborg Hospital, Svendborg, Denmark
  5. 5Reumaklinik Fyn, Odense, Denmark
  6. 6Patient Research Partner, Amsterdam, The Netherlands
  7. 7OPEN – Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark
  8. 8IRS-Center Sønderjylland, University Hospital of Southern Denmark, Aabenraa, Denmark
  9. 9Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
  10. 10Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  11. 11Institute of Metagenomics, BGI-Shenzhen, Shenzhen, China
  12. 12Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
  13. 13Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
  14. 14Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
  1. Correspondence to Professor Torkell Ellingsen, Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital, Odense, Denmark; torkell.ellingsen{at}rsyd.dk

Abstract

Objectives Although 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).

Methods In 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.

Results Of 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%)).

Conclusions In 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 number NCT03058900.

  • arthritis
  • psoriatic
  • therapeutics
  • inflammation

Data availability statement

Data are available upon reasonable request. Requests on data sharing can be made by contacting the corresponding author. Data will be shared after review and approval by the trial scientific board, and terms of collaboration will be reached together with a signed data access agreement.

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Data availability statement

Data are available upon reasonable request. Requests on data sharing can be made by contacting the corresponding author. Data will be shared after review and approval by the trial scientific board, and terms of collaboration will be reached together with a signed data access agreement.

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Footnotes

  • Handling editor Josef S Smolen

  • Twitter @JustSoren

  • Contributors TE, MSK, RC and JK designed the study. MSK and TE were responsible for funding. MSK, DKH and HMH were responsible for donor recruitment, screening and FMT product manufacture. JK and FMP were responsible for the FMT procedure. MSK, TE, HCH, HLM, JKP, PA and SAJ were responsible for patient recruitment. TE, HCH and HLM acquired the clinical data. MSK, SM and RC analysed the clinical data. TE, MSK, RC, JK, HLM, HCH, KK and MW interpreted the results. MSK, TE and RC drafted the report. All authors critically reviewed the report and approved the final version. MSK and TE are guarantors. The corresponding author (TE) attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted.

  • Funding This study was supported 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 (Medicinpuljen), the Region of Southern Denmark Research Fund and Novartis Healthcare (unrestricted grant).

  • Competing interests VA declares personal fees from Merck (MSD) and personal fees from Janssen, outside the submitted work. RC declares a core grant to his institution (Parker Institute, Bispebjerg and Frederiksberg Hospital) from the Oak Foundation (OCAY-18-774-OFIL) and honorariums paid to his institution in relation to the following activities: lecture, research methods (Pfizer, DK; 2017); lecture, GRADE lecture (Celgene, DK; 2017); ad board lecture, CAM (Orkla Health, DK; 2017); project grant: 'GreenWhistle' (Mundipharma, 2019); lecture: diet in RMD (Novartis, DK; 2019); consultancy report, Network MA’s (Biogen, DK; 2017); ad board lecture, GRADE (Lilly, DK; 2017); consultancy report, GRADE (Celgene, 2018); and lecture, Network MA’s (LEO; 2020).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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