Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti–tumor necrosis factor therapy

Authors

  • E. Keystone,

    Corresponding author
    1. University of Toronto, Toronto, Ontario, Canada
    • University of Toronto, Attention: Krista Snow, Mount Sinai Hospital, Joseph and Wolf Lebovic, 2nd Floor Room 006, 600 University Avenue, Toronto, ON, Canada M5G 1X5
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    • Dr. Keystone has received consultant fees, speaking fees, and/or honoraria from Abbott Laboratories, Amgen, Hoffman- LaRoche, Schering-Plough, and UCB (>$10,000 each) and from Bristol-Myers Squibb, Centocor, Genentech, GlaxoSmithKline Beecham, and Wyeth (<$10,000 each).

  • G. R. Burmester,

    1. Charite University Hospital, Berlin, Germany
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    • Dr. Burmester has received consultant fees, speaking fees, and honoraria (less than $10,000) from Roche.

  • R. Furie,

    1. North Shore Long Island Jewish Health System, Great Neck, New York
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    • Dr. Furie has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech, Roche, and Biogen Idec.

  • J. E. Loveless,

    1. Intermountain Orthopedics, Boise, Idaho
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    • Dr. Loveless has received consultant fees (less than $10,000) from the advisory board for Genentech and has received speaking fees (more than $10,000 each) from Genentech and Biogen Idec.

  • P. Emery,

    1. Leeds General Infirmary, Leeds, UK
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    • Dr. Emery has received consultant fees and speaking fees (less than $10,000 each) from Schering-Plough/Centocor, Wyeth/Amgen, Abbott, UCB, Roche, and BMS.

  • J. Kremer,

    1. Center for Rheumatology, Albany, New York
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  • P. P. Tak,

    1. Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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    • Dr. Tak has received consultant fees (less than $10,000 each) from Genentech, Genmab, Merck-Serono, and Roche, and speaking fees and honoraria from Roche.

  • M. S. Broder,

    1. Partnership for Health Analytic Research, LLC, Los Angeles, California
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    • Dr. Broder has received consultancy fees (more than $10,000) from Genentech.

  • E. Yu,

    1. Genentech, South San Francisco, California
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    • Dr. Yu owns stock and/or stock options in Genentech.

  • M. Cravets,

    1. Biogen Idec, San Diego, California
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    • Mr. Cravets owns stock and holds stock options in Biogen Idec.

  • F. Magrini,

    1. University of Milan, Milan, Italy
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    • Dr. Magrini owns stock and/or stock options in Roche.

  • F. Jost

    1. F. Hoffmann-La Roche, Basel, Switzerland
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Abstract

Objective

To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti–tumor necrosis factor therapy.

Methods

Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent-to-treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), and Short Form 36 (SF-36) was determined.

Results

Rituximab patients had statistically significantly greater pain relief. The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean ± SD change from baseline for the SF-36 Physical Component Score was 6.64 ± 8.74 for rituximab patients and 1.48 ± 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF-36 Mental Component Score was 5.32 ± 12.41 for rituximab patients and 2.25 ± 12.23 for placebo patients (P = 0.0269).

Conclusion

Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study.

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