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

Annals of the Rheumatic Diseases - Tập 78 Số 2 - Trang 179-185 - 2019
Daniëlle M. Gerlag1,2, M. Safy1, Karen I. Maijer1, Man Tang1, Sander W. Tas1, Mirian Starmans‐Kool3, Astrid van Tubergen4, M. Janssen5, M. De Hair1, Monika Hansson6, Niek de Vries1, Aeilko H. Zwinderman7, Paul P. Tak7
1Department of Clinical immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands
2Department of Epidemiology and Bioinformatics, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands
3Department of Rheumatology, Zuyderland Medical Centre, Heerlen, The Netherlands
4Division of Rheumatology, Department of Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, The Netherlands
5Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands
6Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
7Division of Clinical immunology and Rheumatology, academic Medical Centre, amsterdam 1105 aZ, The netherlands;

Tóm tắt

ObjectivesWe 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.MethodsIndividuals 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.ResultsEighty-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.ConclusionsA 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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Annals of the Rheumatic Diseases

Tập 78 Số 2

179-185

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