Rheumatoid Arthritis Clinical Studies

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Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial†

  1. Clifton O. Bingham III1,‡,*,
  2. R. John Looney2,§,
  3. Atul Deodhar3,
  4. Neal Halsey4,¶,
  5. Maria Greenwald5,
  6. Christine Codding6,
  7. Benjamin Trzaskoma7,
  8. Flavius Martin7,‖,
  9. Sunil Agarwal7,‖,
  10. Ariella Kelman7,‖

Article first published online: 28 DEC 2009

DOI: 10.1002/art.25034

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 62, Issue 1, pages 64–74, January 2010

Additional Information

How to Cite

Bingham, C. O., Looney, R. J., Deodhar, A., Halsey, N., Greenwald, M., Codding, C., Trzaskoma, B., Martin, F., Agarwal, S. and Kelman, A. (2010), Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial. Arthritis & Rheumatism, 62: 64–74. doi: 10.1002/art.25034

Author Information

  1. 1

    Johns Hopkins University, Baltimore, Maryland

  2. 2

    University of Rochester School of Medicine, Rochester, New York

  3. 3

    Oregon Health & Science University, Portland

  4. 4

    Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

  5. 5

    Desert Medical Advances, Palm Desert, California

  6. 6

    Health Research of Oklahoma, Oklahoma City

  7. 7

    Genentech, South San Francisco, California

  1. ‡

    Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from Genentech and Roche (less than $10,000 each) and grant support from Genentech.

  2. §

    Dr. Looney has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000).

  3. Dr. Halsey has received consulting fees, speaking fees, and/or honoraria from Merck (less than $10,000) and has served on Merck's Data and Safety Monitoring Board.

  4. ‖

    Drs. Martin, Agarwal, and Kelman own stock or stock options in Genentech.

*Division of Rheumatology, Johns Hopkins University, Mason F. Lord Center Tower, Room 404, 5200 Eastern Avenue, Baltimore, MD 21224

  1. †

    ClinicalTrials.gov identifier: NCT00282308.

  2. ‡

    Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from Genentech and Roche (less than $10,000 each) and grant support from Genentech.

  3. §

    Dr. Looney has received consulting fees, speaking fees, and/or honoraria from Genentech (less than $10,000).

  4. Dr. Halsey has received consulting fees, speaking fees, and/or honoraria from Merck (less than $10,000) and has served on Merck's Data and Safety Monitoring Board.

  5. ‖

    Drs. Martin, Agarwal, and Kelman own stock or stock options in Genentech.

Publication History

  1. Issue published online: 28 DEC 2009
  2. Article first published online: 28 DEC 2009
  3. Manuscript Accepted: 8 SEP 2009
  4. Manuscript Received: 4 MAR 2009

Funded by

  • Genentech

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Abstract

Objective

To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab-induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell–dependent antigen), pneumococcal polysaccharide (T cell–independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity (DTH).

Methods

In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a ≥4-fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to C albicans was measured 2–3 days following placement.

Results

Responses to tetanus toxoid vaccine (≥4-fold rise) were similar in both groups (39.1% of rituximab-treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the C albicans skin test was comparable in both groups (77.4% of rituximab-treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab-treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2-fold rise in titer in response to ≥1 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti-KLH IgG, compared with 93% of patients treated with MTX alone).

Conclusion

Recall responses to the T cell–dependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab-treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell–independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses.

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