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Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease
  1. Kevin D Deane1,
  2. V Michael Holers1,
  3. Paul Emery2,3,
  4. Kulveer Mankia2,3,
  5. Hani El-Gabalawy4,
  6. Jeffrey A Sparks5,
  7. Karen H Costenbader5,6,
  8. Georg Schett7,
  9. Annette van der Helm-van Mil8,9,
  10. Dirkjan van Schaardenburg10,
  11. Ranjeny Thomas11,
  12. Andrew P Cope12
  1. 1Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  2. 2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  3. 3NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  4. 4Departments of Medicine and Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  5. 5Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  6. 6Medicine, Harvard Medical School, Boston, Massachusetts, USA
  7. 7Rheumatology, University of Erlangen, Erlangen, Germany
  8. 8Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  9. 9Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands
  10. 10Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands
  11. 11Frazer Institute, University of Queensland, Woolloongabba, Queensland, Australia
  12. 12Academic Department of Rheumatology, Kings College London, London, UK
  1. Correspondence to Professor Andrew P Cope; andrew.cope@kcl.ac.uk

Abstract

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials. Individuals at risk of RA can be identified through population screening, referrals to musculoskeletal programmes and by recognition of arthralgia suspicious for RA. Clinical trials in individuals at risk for future clinical RA have demonstrated that limited courses of corticosteroids, atorvastatin and hydroxychloroquine do not alter incidence rates of clinical RA; however, rituximab delays clinical RA onset, and methotrexate has transient effects in individuals who are anticitrullinated protein antibody-positive with subclinical joint inflammation identified by imaging. Abatacept delays clinical RA onset but does not fully prevent onset of RA after treatment cessation. Additionally, subclinical joint inflammation and symptoms appear responsive to interventions such as methotrexate and abatacept. To advance prevention, next steps include building networks of individuals at risk for RA, to improve risk stratification for future RA and to understand the biological mechanisms of RA development, including potential endotypes of disease, which can be targeted for prevention, thus adopting a more precision-based approach. Future trials should focus on interceptions aimed at preventing clinical RA onset and which treat existing symptoms and imaging-defined subclinical inflammation. These trials may include advanced designs (eg, adaptive) and should be combined with mechanistic studies to further define pathophysiological drivers of disease development.

  • Arthritis, Rheumatoid
  • Autoantibodies
  • Risk Factors
  • Anti-Citrullinated Protein Antibodies
  • Antirheumatic Agents
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/ard-2023-224211

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    Footnotes

    • Handling editor Josef S Smolen

    • X @jeffsparks

    • KDD and VMH contributed equally.

    • Correction notice This article has been corrected since it published Online First. The author's name, Hani El-Gabalawy, has been updated.

    • Contributors KDD, VMH and APC co-wrote the initial version of the manuscript and approved the final version. All other coauthors (PE, KM, HEG, JAS, KHC, GS, AvdH-vM, DvS and RT) contributed to the text of the manuscript and reviewed and approved the final version. KDD is the guarantor of this statement.

    • Funding KDD and VMH work on this manuscript was supported by the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P30 AR07936 and the University of Colorado Autoimmune Disease Prevention Center.

    • Competing interests KDD has received honoraria from BMS, ThermoFisher and Werfen, and in-kind research supplies from Inova Diagnostics; VMH has received equity and funds from Q32 Bio unrelated to this work; PE has received funds for consulting from AnaptysisBio, BMS, Boehringer Ingelheim, Galapagos, Gilead, Janssen, MSD, Lilly, Novartis and support for clinical trials from Abbvie, BMS, Lilly, Novartis and Samsung; KM has received honoraria and/or consulting fees from Abbvie, Lilly, Galapagos, Serac Healthcare, Deepcure, UCB, Zura Bio and research grants from Astra Zeneca, Lilly, Gilead, Serac Healthcare and Deepcure. GS has received funds for consulting from BMS, Janssen and Novartis; JAS has received research support from Boehringer Ingelheim and Bristol Myers Squibb unrelated to this work. He has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer, ReCor, Sobi and UCB unrelated to this work; RT has received funds for consulting from CSL, AbbVie, Nextera, Sandoz, Viela Bio and Janssen-Cilag and received research contracts from CSL and Viela Bio; APC has received consulting and speaker bureau fees from Abbvie, BMS, Galapagos, UCB, Galvani, Janssen, Roche and Arthrogen, and research grant support from BMS, UCB and Janssen, with funds administered by King’s College London.

    • Provenance and peer review Commissioned; externally peer reviewed.