A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus

Authors

  • Daniel J. Wallace,

    Corresponding author
    1. Cedars-Sinai Medical Center, University of California, Los Angeles
    • 8737 Beverly Boulevard, Suite 302, West Hollywood, CA 90048
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  • William Stohl,

    1. University of Southern California Keck School of Medicine and Los Angeles County-University of Southern California Medical Center, Los Angeles
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    • Dr. Stohl has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences.

  • Richard A. Furie,

    1. North Shore-Long Island Jewish Health System, Lake Success, New York
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    • Dr. Furie has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences.

  • Jeffrey R. Lisse,

    1. The University of Arizona Arthritis Center, Tucson
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  • James D. McKay,

    1. Oklahoma Center for Arthritis Therapy and Research, Tulsa
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    • Dr. McKay owns stock and/or holds stock options in Human Genome Sciences.

  • Joan T. Merrill,

    1. Oklahoma Medical Research Center, Oklahoma City
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    • Dr. Merrill has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences, and has served as a paid investment analyst consultant.

  • Michelle A. Petri,

    1. Johns Hopkins University, Baltimore, Maryland
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    • Dr. Petri has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences, and has served as a paid investment analyst consultant.

  • Ellen M. Ginzler,

    1. State University of New York Downstate Medical Center, Brooklyn
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    • Dr. Ginzler has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences, and has served as a paid investment consultant for Guidepoint Global and Gerson Lehrman Group.

  • W. Winn Chatham,

    1. University of Alabama, Birmingham
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  • W. Joseph McCune,

    1. University of Michigan Medical Center, Ann Arbor
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    • Dr. McCune has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech and Johnson & Johnson/Centocor.

  • Vivian Fernandez,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Ms Fernandez and Drs. Zhong and Freimuth own stock and/or hold stock options in Human Genome Sciences.

  • Marc R. Chevrier,

    1. Human Genome Sciences, Inc., Rockville, Maryland
    Current affiliation:
    1. Centocor, Inc., Horsham, Pennsylvania
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    • Dr. Chevrier holds a patent for the definition of systemic lupus erythematosus serologic activity.

  • Z. John Zhong,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Ms Fernandez and Drs. Zhong and Freimuth own stock and/or hold stock options in Human Genome Sciences.

  • William W. Freimuth

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Ms Fernandez and Drs. Zhong and Freimuth own stock and/or hold stock options in Human Genome Sciences.


  • ClinicalTrials.gov identifier: NCT00071487.

Abstract

Objective

To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE).

Methods

Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA–SLEDAI score at week 24 and the time to first SLE flare.

Results

Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA–SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24–52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti–double-stranded DNA [anti-dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA–SLEDAI score (−28.8% versus −14.2%; P = 0.0435), physician's global assessment (−32.7% versus −10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63–71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups.

Conclusion

Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

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