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

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

Author information

1
Department of Clinical immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
2
Department of Epidemiology and Bioinformatics, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
3
Department of Rheumatology, Zuyderland Medical Centre, Heerlen, The Netherlands.
4
Division of Rheumatology, Department of Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, The Netherlands.
5
Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands.
6
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
7
Department of Clinical immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands p.p.tak@amc.nl.

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.

KEYWORDS:

cure; pre-rheumatoid arthritis; prevention; rheumatoid arthritis; rituximab

PMID:
30504445
DOI:
10.1136/annrheumdis-2017-212763
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Conflict of interest statement

Competing interests: PPT is a former employee and DMG a current employee of GlaxoSmithKline, UK. GlaxoSmithKline was not involved in the design and/or execution of the study. NdV reports grants from AbbVie, Janssen Biologics, Ergomed Clinical Research, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, and Roche, as well as personal fees from MSD, UCB, Janssen, non-financial support from Roche, personal fees and non-financial support from Pfizer, all outside the submitted work. In addition, NdV has a patent method for determining the risk of developing arthritis pending. MS reports a research grant from AstraZeneca (received in August 2015). AstraZeneca was not involved in this study.

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