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CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial
  1. Arno W R van Kuijk1,
  2. Clarissa E Vergunst1,
  3. Danielle M Gerlag1,
  4. Barry Bresnihan2,
  5. Juan J Gomez-Reino3,
  6. Rouzier, Regine4,
  7. Patrick C Verschueren5,
  8. Christiaan van de Leij6,
  9. Mario Maas6,
  10. Maarten C Kraan7,
  11. Paul P Tak1
  1. 1Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland
  3. 3Hospital Clinico Universitario, University of Santiago de Compostela, Santiago, Spain
  4. 4Centre CAP, Montpellier, France
  5. 5Division of Rheumatology, Katholieke Universiteit Leuven, Leuven, Belgium
  6. 6Department of Radiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  7. 7Schering-Plough Research Institute, Kenilworth, New Jersey, USA
  1. Correspondence to Paul P Tak, Division of Clinical Immunology and Rheumatology, F4-105, Academic Medical Center/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands; p.p.tak{at}amc.uva.nl

Abstract

Objective C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored.

Methods In this phase Ib randomised, placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in patients with active RA was evaluated. Clinical efficacy was assessed using European League Against Rheumatism and American College of Rheumatology response criteria. ST biopsies were taken before and after 28 days of treatment, and analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were obtained before and after treatment.

Results In all, 32 patients were included; 20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did not complete the study due to adverse events; none of these were serious. No improvement was observed in the active treatment group compared to placebo. Results were consistent for clinical evaluation, ST analysis and MRI.

Conclusion This proof of concept study does not support the use of CCR5 blockade as a therapeutic strategy in patients with active RA.

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Footnotes

  • AWRvK and CEV contributed equally to this work

  • Funding The clinical study was supported by Schering-Plough. DMG was supported by the Dutch Arthritis Association (‘Reumafonds’). This research was also supported by the European Community's FP6 funding (‘Autocure’). This publication reflects only the views of the authors; the European Community is not liable for any use that may be made of the information herein.

  • Competing interests MCK was employed by Schering-Plough. The study was sponsored by Schering-Plough.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committees of all participating centres.

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

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  • Correction
    BMJ Publishing Group Ltd and European League Against Rheumatism