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Ann Rheum Dis 2009;68:216-221 doi:10.1136/ard.2007.085787
  • Clinical and epidemiological research

Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies

  1. E Keystone1,
  2. P Emery2,
  3. C G Peterfy3,
  4. P P Tak4,
  5. S Cohen5,
  6. M C Genovese6,
  7. M Dougados7,
  8. G R Burmester8,
  9. M Greenwald9,
  10. T K Kvien10,
  11. S Williams11,
  12. D Hagerty12,
  13. M W Cravets12,
  14. T Shaw11
  1. 1
    Division of Rheumatology, University of Toronto, Toronto, Canada
  2. 2
    Department of Rheumatology, Leeds General Infirmary, Leeds, UK
  3. 3
    Synarc Inc., San Francisco, California, USA
  4. 4
    Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  5. 5
    St. Paul University Hospital, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  6. 6
    Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA
  7. 7
    Hôpital Cochin, Paris, France
  8. 8
    Charité – University of Medicine Berlin, Berlin, Germany
  9. 9
    Desert Medical Advances, Palm Desert, California, USA
  10. 10
    Diakonhjemmet Hospital, Oslo, Norway
  11. 11
    Roche Products Ltd., Welwyn Garden City, UK
  12. 12
    Biogen Idec Inc., San Diego, California, USA
  1. Professor E Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario, M5G 1X5, Canada; edkeystone{at}mtsinai.on.ca
  • Accepted 24 March 2008
  • Published Online First 3 April 2008

Abstract

Objective: To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors.

Methods: In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56.

Results: Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001).

Conclusions: This study provides the first evidence that a B cell-targeted therapy—rituximab—can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.

Footnotes

  • Competing interests: EK has received consulting and speaker fees from Roche and Genentech and research grants from Roche. PE, PPT, GRB and TKK have received consulting and speaker fees and research grants from Roche. MCG has received speaker fees and research grant support from Roche and has served as a consultant for Roche, Biogen Idec and Genentech. MG has received research funds and consultancy fees from Biogen Idec, Genentech and Roche. DH and MWC are employees of Biogen Idec. SW and TS are employees and own shares in Roche Products Ltd. CGP, SC and MD have not declared any competing interests.

  • Funding: This study was sponsored by F Hoffmann-La Roche Ltd. and Biogen Idec, Inc. A portion of this work (Stanford University) was supported in part by a grant (5 M01 RR000070) from the National Center for Research Resources, National Institutes of Health. The authors are also grateful to the following from Roche Products Ltd: F Magrini, P Lehane, S Safa-Leathers, J Kalsi, A Donohoe, J Smith, K Rowe and B Mistry and the following from Biogen Idec: T Kheoh, K Gilder, J-W Wan, J Torrington and M Weaver.

  • Ethics approval: The study was performed in accordance with the Declaration of Helsinki. All participating sites received approval from their governing institutional review board (or equivalent) and all patients provided written informed consent.

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