EULAR/American College of Rheumatology Risk Stratification Criteria for Development of Rheumatoid Arthritis in the Risk Stage of Arthralgia

Hanna W van Steenbergen¹, Frank Doornkamp², Stefano Alivernini³, John Backlund⁴, Catalin Codreanu⁵, Stanley B Cohen⁶, Bernard Combe⁷, Andrew P Cope⁸, Kevin D Deane⁹, Bryant R England¹⁰, Marie Falahee¹¹, Pascal H P de Jong¹², Arnd Kleyer¹³, Diane Lacaille¹⁴, Bertha Maat¹⁵, Kulveer Mankia¹⁶, Elise van Mulligen¹⁷, György Nagy¹⁸, Liam J O'Neil¹⁹, Linda Rodamaker²⁰, Ilfita Sahbudin²¹, Dirkjan van Schaardenburg²², Alexandre Sepriano²³, Jose A P da Silva²⁴, Lukas De Smet¹, Jeffrey A Sparks²⁵, Ewout W Steyerberg², Paul Studenic²⁶, Elisabeth Wethington²⁷, Robert L Landewé²⁸, Karim Raza²⁹, Annette H M van der Helm-van Mil¹⁷

Affiliations

¹ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
² Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.
³ Division of Rheumatology, Fondazione Policlinico Universita'rio A. Gemelli Istituto di Ricovero e Cura a Carattere.
⁴ At-risk participant.
⁵ Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania.
⁶ University of Texas Southwestern Medical School, Dallas.
⁷ Montpellier University, Montpellier, France.
⁸ Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
⁹ University of Colorado Anschutz Medical Campus, Aurora.
¹⁰ Veterans Affairs Nebraska-Western Iowa Health Care System & University of Nebraska Medical Center, Omaha.
¹¹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
¹² Department of Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands.
¹³ Department of Rheumatology and Clinical Immunology, Charite'-Universitatsmedizin Berlin, Berlin, Germany, and Department of Internal Medicine 3, Rheumatology and Immunology University Hospital Erlangen and Friedrich Alexander University (FAU), Erlangen, Germany.
¹⁴ Arthritis Research Canada, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Patient Research Partner European Alliance of Associations for Rheumatology People with Arthritis and Rheumatism in Europe and National Association ReumaZorg Nederland, The Netherlands.
¹⁶ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds Teaching Hospitals National Health Services Trust, Leeds, UK.
¹⁷ Department of Rheumatology, Leiden University Medical Centre, Leiden, and Department of Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands.
¹⁸ Department of Rheumatology and Clinical Immunology, Department of Internal Medicine and Oncology, Heart and Vascular Center, Department of Genetics, Cell- and Immunobiology, Semmelweis University, and National Institute of Locomotor Diseases and Disabilities, Budapest, Hungary.
¹⁹ Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
²⁰ Department of Rheumatology, University of Colorado School of Medicine, Aurora.
²¹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, and National Institute for Health and Care Research Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
²² Amsterdam Rheumatology Center, Reade, Amsterdam, The Netherlands.
²³ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands, and Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
²⁴ Department of Rheumatology, Centro Hospitalar e Universita'rio de Coimbra, Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Portugal.
²⁵ Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
²⁶ Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria, and Department of Medicine (Solna), Division of Rheumatology, Karolinska Institute, Stockholm, Sweden.
²⁷ Patient research partner, Department of Information Services and Technology, National Jewish Health, Denver, Colorado.
²⁸ Rheumatology & Clinical Immunology, Amsterdam University Medical Center, Amsterdam, and Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.
²⁹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, and Department of Rheumatology, Bronglais Hospital, Hywel Dda University Health Board, Aberystwyth, UK.

PMID: 40343380
DOI: 10.1002/art.43218

EULAR/American College of Rheumatology Risk Stratification Criteria for Development of Rheumatoid Arthritis in the Risk Stage of Arthralgia

Hanna W van Steenbergen et al. Arthritis Rheumatol. 2025.

. 2025 May 8.

doi: 10.1002/art.43218. Online ahead of print.

Authors

Affiliations

¹ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
² Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.
³ Division of Rheumatology, Fondazione Policlinico Universita'rio A. Gemelli Istituto di Ricovero e Cura a Carattere.
⁴ At-risk participant.
⁵ Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania.
⁶ University of Texas Southwestern Medical School, Dallas.
⁷ Montpellier University, Montpellier, France.
⁸ Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
⁹ University of Colorado Anschutz Medical Campus, Aurora.
¹⁰ Veterans Affairs Nebraska-Western Iowa Health Care System & University of Nebraska Medical Center, Omaha.
¹¹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
¹² Department of Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands.
¹³ Department of Rheumatology and Clinical Immunology, Charite'-Universitatsmedizin Berlin, Berlin, Germany, and Department of Internal Medicine 3, Rheumatology and Immunology University Hospital Erlangen and Friedrich Alexander University (FAU), Erlangen, Germany.
¹⁴ Arthritis Research Canada, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ Patient Research Partner European Alliance of Associations for Rheumatology People with Arthritis and Rheumatism in Europe and National Association ReumaZorg Nederland, The Netherlands.
¹⁶ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds Teaching Hospitals National Health Services Trust, Leeds, UK.
¹⁷ Department of Rheumatology, Leiden University Medical Centre, Leiden, and Department of Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands.
¹⁸ Department of Rheumatology and Clinical Immunology, Department of Internal Medicine and Oncology, Heart and Vascular Center, Department of Genetics, Cell- and Immunobiology, Semmelweis University, and National Institute of Locomotor Diseases and Disabilities, Budapest, Hungary.
¹⁹ Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
²⁰ Department of Rheumatology, University of Colorado School of Medicine, Aurora.
²¹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, and National Institute for Health and Care Research Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
²² Amsterdam Rheumatology Center, Reade, Amsterdam, The Netherlands.
²³ Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands, and Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
²⁴ Department of Rheumatology, Centro Hospitalar e Universita'rio de Coimbra, Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Portugal.
²⁵ Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
²⁶ Department of Internal Medicine 3, Division of Rheumatology, Medical University of Vienna, Vienna, Austria, and Department of Medicine (Solna), Division of Rheumatology, Karolinska Institute, Stockholm, Sweden.
²⁷ Patient research partner, Department of Information Services and Technology, National Jewish Health, Denver, Colorado.
²⁸ Rheumatology & Clinical Immunology, Amsterdam University Medical Center, Amsterdam, and Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.
²⁹ Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, and Department of Rheumatology, Bronglais Hospital, Hywel Dda University Health Board, Aberystwyth, UK.

PMID: 40343380
DOI: 10.1002/art.43218

Abstract

Objective: The field of rheumatoid arthritis (RA) is moving towards identification of and intervention in people at risk of RA, but a validated risk stratification method is lacking. This work was undertaken to develop a risk stratification method for persons presenting with arthralgia considered to be at risk of RA.

Methods: A joint EULAR/American College of Rheumatology (ACR) expert committee was established. Risk factor and outcome data from 10 arthralgia cohorts (including clinically suspect arthralgia and autoantibody-positive arthralgia) were studied. The work focused on differentiating the risk of progression to clinically apparent inflammatory arthritis (IA) within 1 year, using clinical and serologic variables, without and with subclinical joint inflammation detected by ultrasound (US) or magnetic resonance imaging (MRI). Developing RA according to the 2010 EULAR/ACR criteria within 1 year was a secondary outcome. A set of validated risk stratification criteria was developed.

Results: Using data from 2,293 symptomatic at-risk individuals, a stratification method was derived consisting of 6 clinical and serologic variables (morning stiffness, patient-reported joint swelling, difficulty making a fist, C-reactive protein, rheumatoid factor, and anti-citrullinated peptide antibody) yielding an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.77-0.83) for IA development. The inclusion of US variables did not increase the discriminative ability. When MRI-detected subclinical inflammation variables were included, the AUC was 0.87 (95% CI 0.82-0.90). In the presence of clinical, serologic, and MRI variables, a sensitivity and specificity of >75% was achieved. For RA development, the AUC of the criteria with MRI was 0.93 (95% CI 0.90-0.97).

Conclusions: EULAR/ACR risk stratification criteria have been developed for people with arthralgia in secondary care who are considered at risk for RA. The criteria can be applied in the absence or presence of imaging data and have been developed to define homogeneous risk groups for future prevention trials.

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References

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EULAR/American College of Rheumatology Risk Stratification Criteria for Development of Rheumatoid Arthritis in the Risk Stage of Arthralgia

Affiliations

EULAR/American College of Rheumatology Risk Stratification Criteria for Development of Rheumatoid Arthritis in the Risk Stage of Arthralgia

Authors

Affiliations

Abstract

References

REFERENCES

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials