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

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

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)179-185
JournalAnnals of the Rheumatic Diseases
Volume78
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019
Externally publishedYes

Cite this

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. / Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: The PRAIRI study. In: Annals of the Rheumatic Diseases. 2019 ; Vol. 78, No. 2. pp. 179-185.
@article{81eb3b9eeb3d46648d4c3e098973768e,
title = "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.",
author = "Gerlag, {Danielle M.} and Mary Safy and Maijer, {Karen I.} and Tang, {Man Wai} and Tas, {Sander W.} and Starmans-Kool, {Mirian J. F.} and {van Tubergen}, Astrid and Matthijs Janssen and {de Hair}, Maria and Monika Hansson and {de Vries}, Niek and Zwinderman, {Aeilko H.} and Tak, {Paul P.}",
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Gerlag, DM, Safy, M, Maijer, KI, Tang, MW, Tas, SW, Starmans-Kool, MJF, van Tubergen, A, Janssen, M, de Hair, M, Hansson, M, de Vries, N, Zwinderman, AH & Tak, PP 2019, 'Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: The PRAIRI study' Annals of the Rheumatic Diseases, vol. 78, no. 2, pp. 179-185. https://doi.org/10.1136/annrheumdis-2017-212763

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

In: Annals of the Rheumatic Diseases, Vol. 78, No. 2, 01.02.2019, p. 179-185.

Research output: Contribution to journalArticleAcademicpeer-review

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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.

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