The primary outcome of the study was time to development of clinical arthritis in subjects in both treatment groups. Clinical arthritis was defined as swollen and tender joints observed by two independent, blinded investigators.
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Researchers found that, compared with placebo, a single infusion of rituximab reduced the baseline risk of arthritis development by 55% at 12 months (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.15 to 1.32; P=0.15) and 53% at 18 months (HR 0.48, 95% CI 0.19 to 1.19). In total, 30 participants developed arthritis. At the point in the study when 25% of subjects had developed arthritis, rituximab treatment caused a delay in arthritis development of 12 months compared with placebo.
Based on the inclusion criteria, Dr. Tak says they are able to identify about 40% of individuals at risk of developing seropositive RA.
“We hypothesize this prediction model can be improved by including body mass index, smoking history, vagus nerve tone and, possibly, such biomarkers as anti-citrullinated alpha-enolase peptide 1 levels,” Dr. Tak says. “Our work also generates new hypotheses about the possible benefit of repeated treatment with a single infusion of rituximab once a year or specific targeting of autoreactive B cells during the preclinical stage of the disease.”
For research application, Dr. Tak believes he and his team are “clearly capable of identifying individuals when they are at risk of developing seropositive RA, but before the onset of arthritis.”
He says this work paves the way for further experimental studies during the “preventive window of opportunity” to optimize prediction models and preventative interventions.
Carina Stanton is a freelance science journalist based in Denver.
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