Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus

Authors

  • Joan T. Merrill,

    Corresponding author
    1. Oklahoma Medical Research Foundation, Oklahoma City
    • Clinical Pharmacology Research Program, MS 22, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104
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    • Drs. Merrill and Wallace have received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline and Human Genome Sciences, Inc. (less than $10,000 each).

  • Ellen M. Ginzler,

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

  • Daniel J. Wallace,

    1. Cedars-Sinai Medical Center and David Geffen School of Medicine, University of California, Los Angeles
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    • Drs. Merrill and Wallace have received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline and Human Genome Sciences, Inc. (less than $10,000 each).

  • James D. McKay,

    1. Oklahoma Center for Arthritis Therapy and Research, Tulsa
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    • Dr. McKay has received consulting fees, speaking fees, and/or honoraria from Human Genome Sciences, Inc. (less than $10,000) and owns stock or stock options in the company.

  • Jeffrey R. Lisse,

    1. Arizona Arthritis Center, University of Arizona, Tucson
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  • Cynthia Aranow,

    1. Feinstein Institute for Medical Research, North Shore–LIJ Health System, Manhasset, New York
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    • Dr. Aranow has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10,000).

  • Frank R. Wellborne,

    1. Houston Institute for Clinical Research, Houston, Texas
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    • Dr. Wellborne has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline and Human Genome Sciences, Inc. (less than $10,000 each) and has received research grants from GlaxoSmithKline and Human Genome Sciences, Inc. for belimumab clinical trials.

  • Michael Burnette,

    1. Tampa Medical Group, Tampa, Florida
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  • John Condemi,

    1. University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Z. John Zhong,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Drs. Zhong, Pineda, Klein, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

  • Lilia Pineda,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Drs. Zhong, Pineda, Klein, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

  • Jerry Klein,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Drs. Zhong, Pineda, Klein, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

  • William W. Freimuth,

    1. Human Genome Sciences, Inc., Rockville, Maryland
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    • Drs. Zhong, Pineda, Klein, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

  • on behalf of the LBSL02/99 Study Group


  • ClinicalTrials.gov identifiers: NCT00071487 and NCT00583362.

Abstract

Objective

To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease.

Methods

Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals.

Results

Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated.

Conclusion

Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile.

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