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Responsiveness to anti-tumour necrosis factor α therapy is related to pre-treatment tissue inflammation levels in rheumatoid arthritis patients
  1. T C van der Pouw Kraan1,
  2. C A Wijbrandts2,
  3. L G van Baarsen1,
  4. F Rustenburg1,
  5. J M Baggen1,
  6. C L Verweij1,
  7. P P Tak2
  1. 1
    VU University Medical Center, Department of Molecular Cell Biology & Immunology, Amsterdam, The Netherlands
  2. 2
    Academic Medical Center/University of Amsterdam, Division of Clinical Immunology and Rheumatology, Amsterdam, The Netherlands
  1. C T M van der Pouw Kraan, VU University Medical Centre, Department of Molecular and Cellular Biology & Immunology, C262, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; t.vanderpouwkraan{at}vumc.nl

Abstract

Objective: The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor α (TNFα) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab.

Methods: Synovial biopsies were obtained by arthroscopy from 18 RA patients with active disease (28 joint count Disease Activity Score (DAS28)⩾3.2) before initiation of treatment with infliximab. All patients were on stable methotrexate treatment. Clinical response at 16 weeks was defined as a reduction in DAS28 of ⩾1.2, non-response as reduction in DAS28 <1.2. Large-scale gene expression profiling using microarrays was performed on synovial tissue samples. To identify biological processes in synovial biopsies that could discriminate between responders and non-responders, we performed pathway analysis on the expression profiles.

Results: A total of 12 patients responded to therapy, while 6 patients failed to fulfil the response criteria. We identified several biological processes, related to inflammation, which were up-regulated in patients who responded to therapy, compared to those who did not show clinical improvement.

Conclusion: These results indicate that patients with a high level of tissue inflammation are more likely to benefit from anti-TNFα treatment.

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Footnotes

  • Funding: This study was supported by a grant from The Netherlands Organization for Health Research and Development (ZonMw) in assignment of The Netherlands Organization for Scientific Research (NWO) (grant number 945-02-029), the European Community’s FP6 funding (Autocure), and the Innovation Oriented research Program (IOP) on Genomics and Centre for Medical Systems Biology (a centre of excellence approved by The Netherlands Genomics Initiative/Netherlands Organization for Scientific Research). This publication reflects only the authors’ views. The European Community is not liable for any use that may be made of the information herein.

  • Competing interests: None.

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