Novel evidence-based systemic lupus erythematosus responder index

Authors

  • Richard A. Furie,

    Corresponding author
    1. North Shore-Long Island Jewish Health System, Lake Success, New York
    • Division of Rheumatology and Allergy-Clinical Immunology, North Shore-Long Island Jewish Health System, 2800 Marcus Avenue, Suite 200, Lake Success, NY 11042
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    • Dr. Furie has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Human Genome Sciences.

  • 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.

  • Daniel J. Wallace,

    1. Cedars-Sinai Medical Center, University of California, Los Angeles
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  • 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.

  • 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.

  • 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.

  • W. Winn Chatham,

    1. University of Alabama, Birmingham
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  • Vibeke Strand,

    1. Stanford University, Palo Alto, California
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    • Dr. Strand has received consultant fees (less than $10,000 each) from Abbott Immunology, Alder, Allergan, Almirall, Amgen Corporation, AstraZeneca, Bexel, BiogenIdec, CanFite, Centocor, Chelsea, Crescendo, Cypress Biosciences, Inc., Euro-Diagnostica, FibroGen, Forest Laboratories, Genentech, Human Genome Sciences, Idera, Incyte, Jazz Pharmaceuticals, Lexicon Genetics, Logical Therapeutics, Lux Biosciences, MedImmune, Merck Serono, Novartis Pharmaceuticals, Novo Nordisk, Nuon, Ono Pharmaceuticals, Pfizer, Procter & Gamble, Rigel, Roche, Sanofi-Aventis, Savient, Schering-Plough, SKK, UCB, Wyeth, and Xdx, and serves on the advisory boards for Abbott, Amgen, BiogenIdec, BMS, CanFite, Centocor, Chelsea, Crescendo, Cypress, Euro-Diagnostica, Fibrogen, Forest, Idera, Incyte, Jazz, Nicox, Novartis, Pfizer, Rigel, Roche, Savient, Schering-Plough, UCB, and Wyeth.

  • Arthur Weinstein,

    1. Washington Hospital Center, Washington, DC
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  • Marc R. Chevrier,

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

  • William W. Freimuth

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


  • ClinicalTrials.gov identifier: NCT00071487.

Abstract

Objective

To describe a new systemic lupus erythematosus (SLE) responder index (SRI) based on a belimumab phase II SLE trial and demonstrate its potential utility in SLE clinical trials.

Methods

Data from a randomized, double-blind, placebo-controlled study in 449 patients of 3 doses of belimumab (1, 4, 10 mg/kg) or placebo plus standard of care therapy (SOC) over a 56-week period were analyzed. The Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG) SLE disease activity instruments, the Short Form 36 health survey, and biomarker analyses were used to create a novel SRI. Response to treatment in a subset of 321 serologically active SLE patients (antinuclear antibodies ≥1:80 and/or anti–double-stranded DNA antibodies ≥30 IU/ml) at baseline was retrospectively evaluated using the SRI.

Results

SRI response is defined as 1) a ≥4-point reduction in SELENA–SLEDAI score, 2) no new BILAG A or no more than 1 new BILAG B domain score, and 3) no deterioration from baseline in the physician's global assessment by ≥0.3 points. In serologically active patients, the addition of belimumab to SOC resulted in a response in 46% of patients at week 52 compared with 29% of the placebo patients (P = 0.006). SRI responses were independent of baseline autoantibody subtype.

Conclusion

This evidence-based evaluation of a large randomized, placebo-controlled trial in SLE resulted in the ability to define a robust responder index based on improvement in disease activity without worsening the overall condition or the development of significant disease activity in new organ systems.

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