Systemic Lupus Erythematosus

You have free access to this content

Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus†

  1. William Stohl1,*,
  2. Falk Hiepe2,‡,
  3. Kevin M. Latinis3,§,
  4. Mathew Thomas4,
  5. Morton A. Scheinberg5,
  6. Ann Clarke6,¶,
  7. Cynthia Aranow7,‖,
  8. Frank R. Wellborne8,††,
  9. Carlos Abud-Mendoza9,
  10. Douglas R. Hough10,‡‡,
  11. Lilia Pineda10,‡‡,
  12. Thi-Sau Migone10,‡‡,
  13. Z. John Zhong10,‡‡,
  14. William W. Freimuth10,‡‡,
  15. W. Winn Chatham11,
  16. on behalf of the BLISS-52 and BLISS-76 Study Groups

Article first published online: 26 JUN 2012

DOI: 10.1002/art.34400

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 64, Issue 7, pages 2328–2337, July 2012

Additional Information

How to Cite

Stohl, W., Hiepe, F., Latinis, K. M., Thomas, M., Scheinberg, M. A., Clarke, A., Aranow, C., Wellborne, F. R., Abud-Mendoza, C., Hough, D. R., Pineda, L., Migone, T.-S., Zhong, Z. J., Freimuth, W. W., Chatham, W. W. and on behalf of the BLISS-52 and BLISS-76 Study Groups (2012), Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis & Rheumatism, 64: 2328–2337. doi: 10.1002/art.34400

Author Information

  1. 1

    Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, Los Angeles

  2. 2

    Charité–Universitätsmedizin Berlin, Berlin, Germany

  3. 3

    University of Kansas Medical Center, Kansas City

  4. 4

    Kerala Institute of Medical Sciences, Trivandrum, Kerala, India

  5. 5

    Hospital Abreu Sodré Pesquisa Clínica, São Paulo, Brazil

  6. 6

    McGill University Health Centre–Montreal General Hospital, Montreal, Quebec, Canada

  7. 7

    The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, New York

  8. 8

    Houston Institute for Clinical Research, Houston, Texas

  9. 9

    Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosi, Mexico

  10. 10

    Human Genome Sciences, Inc., Rockville, Maryland

  11. 11

    University of Alabama at Birmingham

  1. ‡

    Dr. Hiepe has received consulting fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each).

  2. §

    Dr. Latinis has received consulting fees and speaking fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each).

  3. Dr. Clarke has received consulting fees from Human Genome Sciences, Inc. (less than $10,000) and GlaxoSmithKline (more than $10,000).

  4. ‖

    Dr. Aranow has received an honorarium from Human Genome Sciences, Inc. (less than $10,000) for teaching a session at a professional meeting.

  5. ††

    Dr. Wellborne has received consulting fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each) and research support from Human Genome Sciences.

  6. ‡‡

    Drs. Hough, Pineda, Migone, Zhong, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

*Division of Rheumatology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033

  1. †

    ClinicalTrials.gov identifiers: NCT00424476 and NCT00410384.

  2. ‡

    Dr. Hiepe has received consulting fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each).

  3. §

    Dr. Latinis has received consulting fees and speaking fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each).

  4. Dr. Clarke has received consulting fees from Human Genome Sciences, Inc. (less than $10,000) and GlaxoSmithKline (more than $10,000).

  5. ‖

    Dr. Aranow has received an honorarium from Human Genome Sciences, Inc. (less than $10,000) for teaching a session at a professional meeting.

  6. ††

    Dr. Wellborne has received consulting fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each) and research support from Human Genome Sciences.

  7. ‡‡

    Drs. Hough, Pineda, Migone, Zhong, and Freimuth own stock or stock options in Human Genome Sciences, Inc.

Publication History

  1. Issue published online: 26 JUN 2012
  2. Article first published online: 26 JUN 2012
  3. Accepted manuscript online: 24 JAN 2012 03:52PM EST
  4. Manuscript Accepted: 19 JAN 2012
  5. Manuscript Received: 27 SEP 2011

Funded by

  • Human Genome Sciences, Inc. (Rockville, MD)
  • GlaxoSmithKline (Uxbridge, UK)
  • NIH. Grant Number: M01-RR-00043
  • General Clinical Research Center at the University of Southern California Keck School of Medicine

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (460K)

Abstract

Objective

To assess the effects of the B lymphocyte stimulator (BLyS)–specific inhibitor belimumab on immunologic biomarkers, including B cell and T cell populations, and maintenance of antibody titers to prior vaccines in autoantibody-positive systemic lupus erythematosus (SLE) patients.

Methods

Pooled data from 2 phase III trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76-week (BLISS-76) trials, comparing belimumab 1 mg/kg or 10 mg/kg versus placebo (plus standard SLE therapy for each group) were analyzed for changes in autoantibody, immunoglobulin, and complement levels. BLISS-76 patients were also analyzed for changes in B cell and T cell populations and effects on prior vaccine-induced antibody levels.

Results

Belimumab-treated patients experienced significant sustained reductions in IgG and autoantibodies and improvement in C3/C4 levels, resulting in greater positive-to-negative conversion rates for IgG anti–double-stranded DNA (anti-dsDNA), anti-Sm, anticardiolipin, and anti–ribosomal P autoantibodies and normalization of hypergammaglobulinemia and low C3/C4 levels. Belimumab-treated patients experienced significant decreases in the numbers of naive and activated B cells, as well as plasma cells, whereas memory B cells and T cell populations did not decrease. Belimumab did not substantially affect preexisting antipneumococcal or anti–tetanus toxoid antibody levels. Post hoc analysis showed greater reductions in SLE disease activity and the risk of severe flares in patients treated with belimumab 10 mg/kg (P ≤ 0.01) who were anti-dsDNA positive and had low C3/C4 levels at baseline. Normalization of the C3 or anti-dsDNA level by 8 weeks, irrespective of therapy, was predictive of a reduced risk of severe flare over 52 weeks.

Conclusion

Belimumab appears to promote normalization of serologic activity and reduce BLyS-dependent B cell subsets in serologically and clinically active SLE. Greater serologic activity may predict a better treatment response to belimumab.

View Full Article (HTML) Get PDF (460K)