Dr. van Vollenhoven has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Inc., MSD, Pfizer, Roche, and UCB (less than $10,000 each) and was an investigator in the BLISS-52 and BLISS-76 trials.
Systemic Lupus Erythematosus
Baseline Predictors of Systemic Lupus Erythematosus Flares: Data From the Combined Placebo Groups in the Phase III Belimumab Trials†
Version of Record online: 26 JUL 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 8, pages 2143–2153, August 2013
How to Cite
Petri, M. A., van Vollenhoven, R. F., Buyon, J., Levy, R. A., Navarra, S. V., Cervera, R., Zhong, Z. J., Freimuth, W. W. and on behalf of the BLISS-52 and BLISS-76 Study Groups (2013), Baseline Predictors of Systemic Lupus Erythematosus Flares: Data From the Combined Placebo Groups in the Phase III Belimumab Trials. Arthritis & Rheumatism, 65: 2143–2153. doi: 10.1002/art.37995
ClinicalTrials.gov identifiers: NCT00424476 and NCT00410384.
- Issue online: 26 JUL 2013
- Version of Record online: 26 JUL 2013
- Accepted manuscript online: 10 JUN 2013 08:53AM EST
- Manuscript Accepted: 24 APR 2013
- Manuscript Received: 14 NOV 2012
- Human Genome Sciences, Inc.
To identify predictors of moderate-to-severe systemic lupus erythematosus (SLE) flare in 562 patients treated with standard therapy alone in phase III belimumab trials, and to evaluate the impact of standard therapies on preventing flares.
Post hoc analysis assessed baseline demographics, disease activity, and biomarkers in patients with and those without flare at treatment weeks 24 and 52. Severe flare was defined by the modified SLE Flare Index (SFI) and the development of any new British Isles Lupus Assessment Group (BILAG) A domain score. Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores. Baseline characteristics associated with a ≥10% absolute difference or a ≥50% increase in flare rates were considered predictive.
Frequencies of flares over 52 weeks according to the SFI, any new BILAG A domain score, and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7%, 23.1%, and 32.0%, respectively. Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA–SLEDAI); anti–double-stranded DNA (anti-dsDNA) positivity; proteinuria (≥0.5 gm/24 hours); BILAG renal, vasculitic, and hematologic scores; elevated C-reactive protein levels; and B lymphocyte stimulator (BLyS) levels ≥2 ng/ml. Independent predictors by multivariate analysis at week 52 were SELENA–SLEDAI and/or BILAG renal involvement and anti-dsDNA ≥200 IU/ml (on all 3 indices); SELENA–SLEDAI and/or BILAG neurologic and vasculitic involvement (on 2 indices: any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores); BLyS levels ≥2 ng/ml (on 2 indices: the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores); and low C3 level (on the SFI). Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk.
Patients who were receiving standard SLE therapy and had renal, neurologic, or vasculitic involvement, elevated anti-dsDNA or BLyS levels, or low C3 had increased risk of clinically meaningful flare over 1 year. Hydroxychloroquine use was not predictive.