TY - JOUR
T1 - Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: The PRAIRI study
AU - Gerlag, Danielle M.
AU - Safy, Mary
AU - Maijer, Karen I.
AU - Tang, Man Wai
AU - Tas, Sander W.
AU - Starmans-Kool, Mirian J. F.
AU - van Tubergen, Astrid
AU - Janssen, Matthijs
AU - de Hair, Maria
AU - Hansson, Monika
AU - de Vries, Niek
AU - Zwinderman, Aeilko H.
AU - Tak, Paul P.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85057836982&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30504445
U2 - https://doi.org/10.1136/annrheumdis-2017-212763
DO - https://doi.org/10.1136/annrheumdis-2017-212763
M3 - Article
C2 - 30504445
SN - 0003-4967
VL - 78
SP - 179
EP - 185
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 2
ER -