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Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis
  1. R M Thurlings1,
  2. O Teng2,
  3. K Vos1,3,
  4. D M Gerlag1,
  5. L Aarden4,
  6. S O Stapel4,
  7. J M van Laar2,5,
  8. P P Tak1,
  9. G J Wolbink3,4
  1. 1
    Division of Clinical Immunology and Rheumatology, Academic Medical Centre (AMC)/University of Amsterdam, The Netherlands
  2. 2
    Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
  3. 3
    Jan van Breemen Institute, Amsterdam, The Netherlands
  4. 4
    Sanquin Research, Amsterdam, The Netherlands
  5. 5
    Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Professor P P Tak, Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; p.p.tak{at}


Objectives: To analyse whether persistence of synovial B lineage cells and lack of clinical response to rituximab treatment in patients with rheumatoid arthritis (RA) are associated with low rituximab serum levels and anti-rituximab antibody (ARA) formation.

Methods: Fifty-eight patients with RA were treated with rituximab. The clinical response was determined 24 weeks after each treatment course using the Disease Activity Score evaluated in 28 joints (DAS28) and EULAR response criteria. Rituximab serum levels, ARAs and synovial B lineage cell numbers were determined before and after treatment.

Results: Four weeks after treatment rituximab serum levels were highly variable. Low rituximab levels were associated with ARA formation (in five patients (8.6%)) and high baseline erythrocyte sedimentation rate. Interestingly, serum rituximab levels were not related to persistence of synovial B lineage cells or clinical response. Furthermore, response to treatment and re-treatment was similar in ARA-positive and ARA-negative patients.

Conclusion: There is clear variability in serum levels after rituximab treatment, but rituximab levels are not lower in patients with persistence of synovial B lineage cells or lack of clinical response. The current treatment schedule suffices to induce and maintain a clinical response, even when ARAs are formed.

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  • ▸ Additional data are published online only at

  • Funding DMG was supported by the Dutch Arthritis Association (Reumafonds). This research was supported by the European Community’s FP6 funding (Autocure).

  • Competing interests PPT has served as a consultant to Genmab, Genentech, Merck-Serono, and Roche. JMvL has served as a consultant to Encysive and Roche.

  • Ethics approval Approval from the medical ethical committee, Academic Medical Centre, Amsterdam and Leiden University Medical Centre.

  • This publication reflects only the author’s views; the European Community is not liable for any use that may be made of the information herein.

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

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