Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study

• Published in: Annals of the rheumatic diseases Vol. 78; no. 2; pp. 179 - 185
• Main Authors: Gerlag, Danielle M, Safy, Mary, Maijer, Karen I, Tang, Man Wai, Tas, Sander W, Starmans-Kool, Mirian J F, van Tubergen, Astrid, Janssen, Matthijs, de Hair, Maria, Hansson, Monika, de Vries, Niek, Zwinderman, Aeilko H, Tak, Paul P
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.02.2019; BMJ Publishing Group
• Subjects: Adult; Antigens; Antirheumatic Agents - administration & dosage; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - prevention & control; Autoantibodies; Autoantibodies - blood; Autoimmune diseases; B-Lymphocytes - drug effects; Biomarkers; Biomarkers - blood; Biomarkers, Tumor - blood; Blood Sedimentation - drug effects; Citrulline; Cytokines; Disease prevention; DNA-Binding Proteins - blood; Double-Blind Method; Erythrocyte sedimentation rate; Female; Humans; Immunoglobulins; Immunotherapy; Inflammation; Inflammatory diseases; Intervention; Lymphocytes B; Male; Middle Aged; Monoclonal antibodies; Outpatient care facilities; Pathogenesis; Peptides; Phosphopyruvate hydratase; Phosphopyruvate Hydratase - blood; Rheumatoid Arthritis; Rheumatoid factor; Rheumatology; Risk Factors; Rituximab; Rituximab - administration & dosage; Treatment Outcome; Tumor necrosis factor-TNF; Tumor Suppressor Proteins - blood; Netherlands; cure; pre-rheumatoid arthritis; rheumatoid arthritis; prevention; rituximab
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2017-212763

ObjectivesWe explored the effects of B-cell directed therapy in subjects at risk of developing autoantibodypositive rheumatoid arthritis (RA), who never experienced inflammatory arthritis before, and explored biomarkers predictive of arthritis development.MethodsIndividuals positive for both anti-citrullinated peptide antibodies and rheumatoid factor but without arthritis were included in a randomised, double-blind, placebo-controlled study to receive a single infusion of 1000 mg rituximab or placebo.ResultsEighty-one individuals received treatment and were followed up for a mean of 29.0 (0–54) months, during which 30/81 (37%) individuals developed arthritis. The observed risk of developing arthritis in the placebo-treated group was 40%, which was decreased by 55% (HR 0.45, 95% CI 0.154 to 1.322) in the rituximab-treated group at 12 months. Rituximab treatment caused a delay in arthritis development of 12 months compared with placebo treatment at the point when 25% of the subjects had developed arthritis (p<0.0001). Erythrocyte sedimentation rate and the presence of anti-citrullinated α-enolase peptide 1 at baseline were significant predictors of arthritis development.ConclusionsA single infusion of 1000 mg rituximab significantly delays the development of arthritis in subjects at risk of developing RA, providing evidence for the pathogenetic role of B cells in the earliest, prearthritis stage of autoantibody positive RA.