Gerlag and fellow researchers1 in the Netherlands have discovered that by targeting B cells with rituximab in patients at increased risk for rheumatoid arthritis (RA) later in life, the signs and symptoms of arthritis can be delayed.
B cells and RA
Antibody-positive RA is often preceded by a phase of systemic autoimmunity characterized by circulating autoantibodies, acute-phase reactants, pro-inflammatory cytokines, and chemokines. IgM rheumatoid factor (IgM-RF), anti-citrullinated peptide antibodies (ACPA), and other RA-specific antibodies can be detected in blood samples of patients who later receive a diagnosis of seropositive RA, with a median of 5 years before arthritis becomes evident.
It is clear that B cells play an important role leading up to clinical RA. The authors sought to determine whether B-cell depletion could alter the development of RA in persons at high risk as well as to identify biomarkers predictive of arthritis development.
The authors conducted the Prevention of Clinically Manifest Rheumatoid Arthritis by B-Cell Directed Therapy In the Earliest Phase of Disease Study (PRAIRI), a phase IIb, randomized, double-blind, placebo-controlled investigation that looked at 82 patients with arthralgia but no evidence of clinical arthritis. Subjects were randomized to receive either rituximab 1000 mg once or placebo.
The participants were adults without inflammatory arthritis or previous antirheumatic drug use who had baseline C-reactive protein levels higher than 0.6 mg/L or subclinical synovitis. They were monitored for clinical arthritis thereafter.
Next: the results and take-home points for clinicians
1. Gerlag DM, Safy M, Maijer KI, et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2018 Dec 1. pii: annrheumdis-2017-212763. doi:10.1136/annrheumdis-2017-212763. [Epub ahead of print]