Rheumatoid Arthritis


Identifying Patients at Risk of Developing Rheumatoid Arthritis

patient care perspectives


Interest in understanding the earliest pathophysiology of rheumatoid arthritis (RA) and the risk factors that drive the development of disease is expanding. Our featured expert discusses the key risk factors for the development of RA and examines the proper management of patients with preclinical RA.

Expert Commentary

James O’Dell, MD, MACR, MACP

Stokes Shackleford Distinguished Professor
Chief, Division of Rheumatology and Vice Chair for Education, Department of Internal Medicine
Director, Internal Medicine Residency Program
University of Nebraska Medical Center
Founder and Director, Rheumatoid Arthritis Investigational Network
Omaha, NE

“Data from SERA and from other cohorts indicate that the development of positive anti-CCP antibody titers may precede the onset of clinical disease by many, many years.” 

James O’Dell, MD, MACR, MACP

There has been a growing interest in identifying patients earlier in the course of RA because early intervention may be a more effective approach for slowing disease progression than waiting until later in the disease course. Preclinical RA can be defined retrospectively as the presence of serologic evidence of RA in the absence of clinical symptoms of RA. Currently, the most reliable screening tool to identify people at risk for RA is anti-cyclic citrullinated peptide (anti-CCP) antibody testing. Data from the Studies of the Etiology of Rheumatoid Arthritis (SERA) have shown that patients with elevated anti-CCP antibodies (ACPAs) have a significant increased risk of developing RA at some point in the future. Individuals with preclinical RA also develop a broader spectrum of ACPAs, a phenomenon referred to as epitope spreading, which more closely anticipates the clinical onset of RA. Data from SERA and from other cohorts indicate that the the development of positive anti-CCP antibody titers may precede the onset of clinical disease by many, many years. This begs the question of how best to manage preclinical RA. We have some indications that, particularly related to the development of RA, encouraging a healthy lifestyle is appropriate. Data, including those from the Brigham and Women’s Hospital and Harvard Medical School, suggest that an inflammatory dietary pattern is associated with an increased risk of developing RA. We also know that cigarette smoking is a risk factor for the development of RA, so we can encourage our patients to adopt healthier diets and to stop smoking. In addition, the ongoing Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA) trial is evaluating whether the use of hydroxychloroquine is safe and effective for the prevention of future-onset RA in individuals who have elevated ACPAs. We do not yet know how to intervene effectively, so, while widespread screening and treatment of populations at risk for developing clinical RA is not currently practical, we hope that future research will identify effective preventive strategies such that we will be able to screen appropriate individuals (eg, first-degree relatives of patients with RA) and to offer a safe and effective treatment regimen that prevents or slows disease onset.


ClinicalTrials.gov. Strategies to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA). Available at https://clinicaltrials.gov/ct2/show/NCT02603146. Accessed September 15, 2018.

Demoruelle MK, Parish MC, Derber LA, et al. Anti-cyclic citrullinated peptide assays differ in subjects at elevated risk for rheumatoid arthritis and subjects with established disease. Arthritis Rheum. 2013;65(9):2243-2252.

Hughes-Austin JM, Deane KD, Derber LA, et al. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA). Ann Rheum Dis. 2013;72(6):901-907.

Karlson EW, van Schaardenburg D, van der Helm-van Mil AH. Strategies to predict rheumatoid arthritis development in at-risk populations. Rheumatology (Oxford). 2016;55(1):6-15.

Nielen MM, van Schaardenburg D, Reesink HW, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004;50(2):380-386.

Sparks JA, Barbhaiya M, Tedeschi SK, et al. Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women. Clin Rheumatol. 2018;Aug 14: doi: 10.1007/s10067-018-4261-5. [Epub ahead of print]

van Zanten A, Arends S, Roozendaal C, et al. Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands. Ann Rheum Dis. 2017;76(7):1184-1190.