Rituximab may delay RA onset in at-risk individuals
medwireNews: Findings from the PRAIRI trial suggest that a single infusion of the B-cell directed agent rituximab could delay the development of rheumatoid arthritis (RA) among individuals positive for anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF).
Previous research has demonstrated that these autoantibodies “can be found in the peripheral blood of individuals >10 years before the development of autoantibody positive rheumatoid arthritis”, indicating that there may be “an opportunity to potentially delay the clinical onset of disease by a targeted intervention in this early phase”, explain Paul Tak (Academic Medical Centre, Amsterdam, the Netherlands) and co-investigators.
In their phase IIb trial, the researchers randomly assigned 81 participants with arthralgia and ACPA/RF positivity but with no evidence of clinical arthritis to receive one intravenous infusion of rituximab 1000 mg or placebo. All patients were given methylprednisolone 100 mg prior to receiving the study drug in order to prevent infusion-related adverse events.
As reported in the Annals of the Rheumatic Diseases, 37% of participants developed RA over an average follow-up of 29.0 months. Compared with patients given placebo, those in the rituximab group were 55% less likely to have RA after 12 months of follow-up and 52% less likely to have the disease after 18 months.
Moreover, treatment with rituximab led to a significant delay in the time taken for 25% of patients to develop arthritis, at 2 years versus 1 year in the placebo group.
The investigators note, however, that “[t]he observed effect on delaying arthritis development attenuated over time.”
Indeed, the risk of RA onset over the total study period was not significantly different between the two groups. A total of 34% of rituximab-treated patients developed RA over a median of 16.5 months, whilst 40% of those in the placebo group were diagnosed with the condition over a median of 11.5 months.
The study authors also carried out an exploratory biomarker analysis, demonstrating that erythrocyte sedimentation rate and the presence of anti-citrullinated α-enolase peptide 1 at baseline were significantly associated with the development of RA during follow-up.
Tak and colleagues report that rituximab “was generally well tolerated” in the trial, with no patients requiring hospitalisation due to serious infection. A significantly higher proportion of patients treated with rituximab versus placebo experienced serious adverse events (31.7 vs 7.5%), but all such events were considered unrelated to treatment allocation by the safety monitoring board.
Together, these findings support the existence of “a preventive window of opportunity” before the signs and symptoms of RA develop, say the researchers.
They conclude 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.”
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