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

Abstract

OBJECTIVES:

We 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.

METHODS:

Individuals 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.

RESULTS:

Eighty-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.

CONCLUSIONS:

A 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.

• Authors: Danielle M Gerlag, Mary Safy, Karen I Maijer, Man Wai Tang, Sander W Tas, Mirian J F Starmans-Kool, Astrid van Tubergen, Matthijs Janssen, Maria de Hair, Monika Hansson, Niek de Vries, Aeilko H Zwinderman, Paul P Tak
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 78 Issue 2 Pg. 179-185 (02 2019) ISSN: 1468-2060 [Electronic] England
• PMID: 30504445 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antirheumatic Agents
• Autoantibodies
• Biomarkers
• Biomarkers, Tumor
• DNA-Binding Proteins
• Tumor Suppressor Proteins
• Rituximab
• ENO1 protein, human
• Phosphopyruvate Hydratase

Topics

• Adult
• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (immunology, prevention & control)
• Autoantibodies (blood)
• B-Lymphocytes (drug effects)
• Biomarkers (blood)
• Biomarkers, Tumor (blood)
• Blood Sedimentation (drug effects)
• DNA-Binding Proteins (blood)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Phosphopyruvate Hydratase (blood)
• Risk Factors
• Rituximab (administration & dosage)
• Treatment Outcome
• Tumor Suppressor Proteins (blood)