Dr. Hiepe has received consulting fees from Human Genome Sciences, Inc. and GlaxoSmithKline (less than $10,000 each).
Systemic Lupus Erythematosus
Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus†
Version of Record online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2328–2337, July 2012
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
ClinicalTrials.gov identifiers: NCT00424476 and NCT00410384.
- Issue online: 26 JUN 2012
- Version of Record online: 26 JUN 2012
- Accepted manuscript online: 24 JAN 2012 03:52PM EST
- Manuscript Accepted: 19 JAN 2012
- Manuscript Received: 27 SEP 2011
- 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
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.
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.
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.
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.