EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Kulveer Mankia; Heidi J Siddle; Andreas Kerschbaumer; Deshire Alpizar Rodriguez; Anca Irinel Catrina; Juan D Cañete; Andrew P Cope; Claire Immediato Daien; Kevin D Deane; Hani El Gabalawy; Axel Finckh; V Michael Holers; Marios Koloumas; Francesca Ometto; Karim Raza; Condruta Zabalan; Annette van der Helm-van Mil; Dirkjan van Schaardenburg; Daniel Aletaha; Paul Emery

doi:10.1136/annrheumdis-2021-220884

EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Ann Rheum Dis. 2021 Oct;80(10):1286-1298. doi: 10.1136/annrheumdis-2021-220884. Epub 2021 Aug 6.

Authors

Kulveer Mankia^{1

2}, Heidi J Siddle^{3

2}, Andreas Kerschbaumer⁴, Deshire Alpizar Rodriguez⁵, Anca Irinel Catrina⁶, Juan D Cañete⁷, Andrew P Cope⁸, Claire Immediato Daien⁹, Kevin D Deane¹⁰, Hani El Gabalawy¹¹, Axel Finckh¹², V Michael Holers¹³, Marios Koloumas¹⁴, Francesca Ometto¹⁵, Karim Raza^{16

17}, Condruta Zabalan¹⁴, Annette van der Helm-van Mil^{18

19}, Dirkjan van Schaardenburg^{20

21}, Daniel Aletaha²², Paul Emery^{23

24}

Affiliations

¹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK k.s.mankia@leeds.ac.uk.
² NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds, UK.
³ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
⁴ Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
⁵ Research Unit, Mexican College of Rheumatology, Coyoacan, Mexico.
⁶ Rheumatology Unit, -, Stockholm, Sweden.
⁷ Department of Rheumatology, Arthritis Unit, Hospital Clinic and IDIBAPS, Barcelona, Spain.
⁸ Faculty of Life Sciences and Medicine, Centre for Rheumatic Diseases, King's College London, London, UK.
⁹ Department of Rheumatology, CHU de Montpellier, University of Montpellier, PhyMedExp, INSERM, CNRS UMR, Montpellier, France.
¹⁰ Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
¹² Division of Rheumatology, University of Geneva, Geneva, Switzerland.
¹³ Division of Rheumatology, Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁴ EULAR PARE, Kilchberg, Switzerland.
¹⁵ Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy.
¹⁶ Centre for Musculoskeletal Ageing Research and Research into Inflammatory Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
¹⁷ Department of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
¹⁸ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁹ Department of Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands.
²⁰ Department of Rheumatology, Academic Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
²¹ Department of Rheumatology, Reade, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.
²² Department of Rheumatology, Medical University of Vienna, Vienna, Austria.
²³ Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.
²⁴ NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Abstract

Background: Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).

Methods: An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1-10) for each PTC.

Results: Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants' knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.

Conclusion: These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

Keywords: arthritis; autoantibodies; autoimmunity; rheumatoid.

Publication types

Guideline
Research Support, Non-U.S. Gov't

MeSH terms

Antirheumatic Agents / therapeutic use
Arthritis, Rheumatoid / diagnostic imaging
Arthritis, Rheumatoid / immunology
Arthritis, Rheumatoid / prevention & control*
Arthritis, Rheumatoid / therapy
Asymptomatic Diseases*
Clinical Trials as Topic / methods*
Europe
Humans
Observational Studies as Topic / methods*
Rheumatology
Risk Factors
Severity of Illness Index
Societies, Medical

Substances

Antirheumatic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding