Targeting B cells may delay RA development in those at risk
medwireNews: B-cell directed therapy with a single infusion of rituximab significantly delays the development of rheumatoid arthritis (RA) in people at high risk for developing the condition, exploratory study data show.
Paul Tak (Academic Medical Centre, Amsterdam, the Netherlands) and co-authors say their findings “support the view that it may be easier to control the disease process by targeted intervention before signs and symptoms of arthritis have developed, which suggests the existence of a ‘preventive window of opportunity’.”
During a mean follow-up period of 29.0 months, RA developed in 34% of 41 individuals positive for both anti-citrullinated peptide antibodies and rheumatoid factor but without evidence of clinical arthritis who were randomly assigned to receive a single infusion of rituximab 1000 mg as part of the phase IIb PRAIRI study.
This was not significantly lower than the 40% incidence rate observed among 40 participants randomly assigned to receive placebo.
However, the researchers say that although the study did not meet their initial goal of a reduction in RA incidence from 40% to 10%, “the treatment resulted in markedly delayed onset of disease rather than cure.”
Specifically, the point at which 25% of participants had developed RA was delayed significantly from 12 months in the placebo group to 24 months in the rituximab group.
The effect rituximab had on delaying RA development reduced over the course of the study, which Tak and colleagues suggest may be due to “persistence of autoreactive B-cell clones in the tissues and subsequent repopulation over time.”
“It is tempting to speculate that repeated treatment, perhaps with a single infusion of rituximab once a year, might be sufficient to control B-cell numbers and prevent clinically manifest disease in a population at high risk of developing RA, whereas a more sophisticated approach would be to specifically target the autoreactive B cells that drive autoimmunity during the preclinical stage of the disease,” they add.
An analysis of clinical and serologic biomarkers showed that the only significant predictors of RA developments were erythrocyte sedimentation rate and the presence at baseline of anti-citrullinated α-enolase peptide 1.
Tak et al conclude in the Annals of the Rheumatic Diseases that their results “are clearly consistent with the critical role of B cells in the pathogenesis of RA during the earliest stages of the disease and support future studies aimed at secondary prevention of RA, including by the use of targeted treatments.”
By Laura Cowen
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