Researchers Work Toward Early ID & Treatment of Rheumatoid Arthritis

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AMSTERDAM—Early identification and treatment of rheumatoid arthritis (RA) are two of the most pressing concerns in the field, an expert said at EULAR: the Annual European Congress of Rheumatology. He described the latest efforts to identify patients at risk of RA development and insights on quick referral to rheumatologists.

Karim Raza, BM, BCh, PhD, Arthritis Research UK professor of rheumatology at the University of Birmingham in the United Kingdom, said a major challenge is discerning which patients with early, undifferentiated RA or clinically suspect arthralgia will go on to develop RA.

Total IgG Glycosylation

In an analysis of data from the Leiden Early Arthritis Cohort, researchers looked at those who were classified as having undifferentiated RA under the 1987 criteria and then developed RA within one year under those criteria.¹ They asked: Would the 2010 criteria perform better, capturing at baseline those who would have progressed to RA? They found the 2010 criteria tended to capture those who were positive for anti-citrullinated protein antibody (ACPA), rheumatoid factor or both. But it did not tend to capture those patients who were negative for both.

“The issue relates to the seronegative group,” Dr. Raza said. “This is really where the biggest problem arises—for seronegative early undifferentiated arthritis. … This is a group for which there is a need for a better understanding for how to predict who will go on to develop a persistent disease, such as RA.”

Research has found that other RA-associated antibody classes measured at baseline, for example anti-carbamylated protein antibody, do not tend to do well in predicting RA progression for patients who are seronegative for ACPA and RF, he said.²

A hopeful note may be found in the study of sugar residues that coat autoantibodies and antibodies in general. Researchers in China have developed an assay that can detect very low levels of N-glycans on total immunoglobulin. They found that total IgG glycosylation with these glycans is different from RA patients than controls, even among those who are ACPA- and RF-negative.³ This test performs well, with a high predictive value for RA, they said.

Dr. Raza

“This gives us an antibody-based biomarker that’s not dependent upon the traditional RA-associated antibodies,” Dr. Raza said. “I think this is likely to be a space that we need to watch over the next few years.”

Tenosynovitis

In other research, investigators looked systematically to see whether identifying teno­synovitis gave added value over synovitis for the prediction of RA development in patients with very early arthritis. And they found that it does.⁴ Clinicians also struggle with how to proceed with patients who have “clinically suspect arthralgia”—those who don’t have swollen joints, but who have “inflammatory-sounding” joint symptoms that prompt concern about potential RA development.