Windows of Opportunity for Preclinical Rheumatoid Arthritis

Rheumatoid arthritis (RA) affects more than 1.5% of the world’s population.¹ One forecast suggests that practitioner-diagnosed rheumatoid arthritis will increase by 49% by 2040 due to an aging population—that’s over one quarter of adults diagnosed.² One in four US adults are forecast to have rheumatoid arthritis by 2040.²

Genetic and environmental factors play a role in the development and the progression of the disease. Before the condition emerges, patients enter a pro-inflammatory state. Heritability estimates for RA range from 53-65%.^3-4 There are close to 60 genetic loci associated with susceptibility to RA across multiple populations.⁴ These loci are at least partially shared across ethnicities.³ Several changes in the synovial fluid of RA patients seem to increase cytokines and promote a pro-inflammatory state.⁵

Preclinical autoantibodies

The preclinical phase of RA often involves increased production of autoantibodies, which are detectable more than 10 years before RA can be diagnosed.^6-7 In one study of patients with musculoskeletal complaints, those patients with the highest levels of antibodies at baseline had a 62% increased likelihood of RA diagnosis at five years.⁸ In a cohort study of healthy relatives of those suffering from arthritis, anticyclic citrullinated peptide (anti-CCP) antibody levels at baseline had positive predictive value of 68% for RA diagnosis at five years.⁹ This “preclinical” stage¹⁰ offers opportunities to intervene early.¹¹

One review article has emphasized that early intervention may at least delay and might sometimes prevent the onset of rheumatoid arthritis.¹² This highlights the need to help susceptible patients modify their lifestyle to reduce the risk of disease progression.¹³ As an inflammatory-mediated disease, rheumatoid arthritis is preceded by systemic autoimmunity, and then, the hypothesis goes, a trigger causes synovial inflammation that begins the RA-specific disease process.¹⁴

What factors tip the scale to cause or prevent RA? In the following video, IFM Executive Director of Medical Education Robert Luby, MD, describes some of the known precursors to the development of RA.