Ingrid Hein
June 18, 2018

AMSTERDAM — A blood test for people at risk for rheumatoid arthritis can identify those who will develop the disease within 3 years, new research shows.

“Our data support a new biomarker that demonstrates better predictive power than other biomarkers evaluated so far,” said investigator Anne Musters, MD, from the Amsterdam Rheumatology and Immunology Center.

The findings confirm results from a study of 21 people with autoantibodies indicating risk for rheumatoid arthritis (Ann Rheum Dis. 2017;76:1924-1930). The presence of at least five dominant B-cell receptor (BCR) clones in peripheral blood predicted the short-term onset of rheumatoid arthritis.

“We think that peripheral BCR clones can be used to identify at-risk individuals who will go on to develop arthritis,” Musters said in a statement. This information could be used to evaluate “early interventions to prevent the onset of disease.”

In their study, Musters and her colleagues used next-generation sequencing to evaluate BCR clones in 129 people with joint pain and rheumatoid arthritis-specific antibodies.

Of these, 45 people tested positive— defined as at least five dominant BCR clones — and 84 tested negative.

During the 104-month follow-up period, patients in the positive group were more likely to develop rheumatoid arthritis than those in the negative group (76% vs 13%; relative risk, 5.8; 95% confidence interval, 3.2 – 10.3; P < .0001).

“This test works perfectly in helping us predict who will develop rheumatoid arthritis and might need treatment,” said investigator Niek de Vries, MD, PhD, also from the Amsterdam Rheumatology and Immunology Center, who presented the study results here at the European League Against Rheumatism Congress 2018.

In addition, the more BCR clones, “the higher the risk of imminent-onset arthritis,” he reported. Having nine or more dominant BCR clones in the blood corresponded with a positive predictive value of 91% for development within 3 years.

In about half the patients with at least nine clones, the disease developed in a little more than 1 year, and practically all had rheumatoid arthritis after 3.5 years, de Vries said.

Studies have shown that early treatment is more effective than delayed treatment and that treatment can delay disease onset. “If you know a patient is going to get rheumatoid arthritis, why not start treating them early?” he asked.

“The best way to treat seropositive rheumatoid arthritis is to prevent it,” he told Medscape Medical News.

But not everyone thinks treatment before disease onset is a good idea.

There are definitely psychological risks to the patient.
“If you could prevent rheumatoid arthritis, this would be splendid,” said Berit Jensen Grandaunet, MD, PhD, from St. Olavs Hospital in Trondheim, Norway. “But this is not a treatment that will prevent the onset of disease.”

“There are definitely psychological risks to the patient,” including distress at the imminent onset of disease, she explained. There are also possible adverse effects related to treatment, such as an increased risk for infection.

And sequencing is not a standard method of testing in most hospitals. “You probably wouldn’t have access in publicly funded hospitals because of the cost,” so the test would only be available in private clinics, Grandaunet pointed out.

This kind of testing could theoretically get patients on treatment early, but would that really be possible, she wondered.

“If you could get them immediately after they experience swollen joints, that would be nice,” she said. “Still, I’m not sure it’s the right thing to do because of the possible psychological stress.”

Musters and Grandaunet have disclosed no relevant financial relationships. de Vries reports receiving grant or research support from the Innovative Medicines Initiative, the Center for Translational Molecular Medicine, LSH, Pfizer, Roche, Janssen, GSK, and has worked as a consultant for UCB and MSD.

European League Against Rheumatism (EULAR) Congress 2018: Abstract OP0204. Presented June 14, 2018.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein

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