Rheumatoid Arthritis Research Provides New Insights on Risk Factors, Identification Tools, Intervention

Research is underway to help determine which patients may be most likely to move to the final phase of pathological disease, and what interventions could be most helpful.
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Established wisdom holds that patients with rheumatoid arthritis (RA) will fare better if their disease is diagnosed as early as possible, and treatments with disease-modifying drugs are started before inflammation can do more damage to joints and tissue. Usually, early diagnosis means spotting the clinical signs of disease, but new research tells us more about possible clues that present even earlier.

Individuals at risk for RA move along a spectrum of six phases, potentially triggering factors and events that lead to diagnosed disease, according to a chart created by the European League Against Rheumatism (EULAR) Standing Committee on Investigative Rheumatology.¹ These phases are possible signposts to alert rheumatologists to either track certain patients more closely, or even intervene with therapy, say arthritis researchers Kulveer Mankia, MA, MCRP, and Paul Emery, MA, MD, FRCP, FMedSci, both at the Leeds Institute of Rheumatic and Musculoskeletal Medicine in the United Kingdom.

Prof. Emery

In their paper, “Preclinical Rheumatoid Arthritis: Progress Toward Prevention,” published in Arthritis & Rheumatology in April, they delve into the latest research on genetic and environmental risk factors, events that may set localized autoimmunity in motion, which patients may be most likely to move to the final phase of pathological disease, and what interventions could be most helpful.²

“Preclinical, systemic autoimmunity definitely occurs,” says Prof. Emery. “Identifying individuals with the presence of autoantibodies against citrullinated proteins is the main method of identifying patients in a preclinical phase.”

Not every patient, even those who get to the third phase of the spectrum, systemic autoimmunity, becomes symptomatic or develops clinical arthritis, he adds. Thus, terms like preclinical RA or pre-RA should be used only to look back at earlier signs once disease is confirmed. Recent advances in both diagnostic tools and our understanding of autoimmunity may allow rheumatologists to stop the process before a patient exhibits pathological changes.

“To intervene early, it is necessary to have predictors of imminent RA,” says Prof. Emery. “In a number of papers, we have now identified particular imaging and immunological abnormalities as accurate predictors.”^3,4

Baseline Risk Factors

Individuals who reach the third of the six phases on the road from risk to RA, immune dysregulation or systemic autoimmunity, may be first experiencing those pathological changes, according to Ms. Mankia and Prof. Emery. We can now flag an even wider group of people as having the potential to develop RA because they are in the first phase, those with genes associated with RA susceptibility, or the second, exposure to environmental triggers that could spark localized autoimmunity.