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

Ann Rheum Dis. 2019 Feb;78(2):179-185. doi: 10.1136/annrheumdis-2017-212763. Epub 2018 Dec 1.


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.

Keywords: cure; pre-rheumatoid arthritis; prevention; rheumatoid arthritis; rituximab.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / 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


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