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Rheumatoid arthritis
Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study
  1. Danielle M Gerlag1,2,
  2. Mary Safy1,
  3. Karen I Maijer1,
  4. Man Wai Tang1,
  5. Sander W Tas1,
  6. Mirian J F Starmans-Kool3,
  7. Astrid van Tubergen4,
  8. Matthijs Janssen5,
  9. Maria de Hair1,
  10. Monika Hansson6,
  11. Niek de Vries1,
  12. Aeilko H Zwinderman,
  13. Paul P Tak1
  1. 1 Department of Clinical immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands
  2. 2 Department of Epidemiology and Bioinformatics, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centre, Amsterdam, The Netherlands
  3. 3 Department of Rheumatology, Zuyderland Medical Centre, Heerlen, The Netherlands
  4. 4 Division of Rheumatology, Department of Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, The Netherlands
  5. 5 Department of Rheumatology, Rijnstate Hospital, Arnhem, The Netherlands
  6. 6 Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Professor Paul P Tak, Division of Clinical Immunology and Rheumatology, Academic Medical Centre, Amsterdam 1105 AZ, The Netherlands; p.p.tak{at}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.

  • prevention
  • cure
  • rheumatoid arthritis
  • rituximab
  • pre-rheumatoid arthritis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/annrheumdis-2017-212763

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    Footnotes

    • Handling editor Josef S Smolen

    • Presented at This work was previously presented at ACR 2016.

    • Correction notice This article has been corrected since it published Online First. The competing interest statement, abstract conlcusion and reference 20 have been updated.

    • Contributors PPT was the principal investigator, and was responsible for the study design, data interpretation and writing of the report. DMG and KIM contributed to the study design, data collection, data analysis, data interpretation and writing of the report. MS contributed to the data collection, data analysis, data interpretation and writing of the report. MWT, SWT, MdH, MJFSK, AvT, MJ, MH and NdV contributed to data collection and writing of the report. AHZ was responsible for data analysis, interpretation of the data and writing of the report.

    • Funding Funding was received from the Dutch Arthritis Foundation (grant number 11-1-407); Netherlands Organisation for Health Research and Development (ZonMw; grant number 200310003); European Union Seventh Framework Programme (project EuroTEAM; grant number FP7-HEALTHF2-2012-305549); IMI EU-funded project BeTheCure (grant number 115142).

    • 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.

    • Patient consent for publication Not required.

    • Ethics approval The Medical Ethics Research Committee of the Academic Medical Centre of the University of Amsterdam, The Netherlands.

    • Provenance and peer review Not commissioned; externally peer reviewed.