Post-hoc analysis of data from phase III clinical trials of belimumab (Benlysta) suggests factors that predict flares among patients taking conventional treatment for lupus.
Petri MA, van Vollenhoven RF, Buyon J, et al. on behalf of the BLISS-52 and BLISS-76 Study Groups. Baseline Predictors of Systemic Lupus Erythematosus Flares: Data From the Combined Placebo Groups in the Phase III Belimumab Trials. Arthritis & Rheumatism. (2013) 65:2143–2153
Post-hoc analysis of two phase III clinical trials of belimumab (Benlysta), now FDA-approved for systemic lupus erythematosus (SLE), hints at the factors that predict flares among patients with active SLE on conventional treatment -- and that none of those therapies appears to affect flare risk more than another.
Predictors of moderate to severe flares at 24 and 52 weeks include renal, neurologic, or vasculitic involvement. However, conventional therapies do not appear to affect flare risk.
In the original trials 1,684 patients -- 865 in the 52-week trial (BLISS-52) and 819 in the 76-week trial (BLISS-76) -- were randomized to standard SLE therapy (e.g., corticosteroids, immunosuppressives, antimalarials) plus placebo or to belimumab at 1 or 10 mg/kg.
For the post-hoc analysis, baseline characteristics, disease activity, demographics, and biomarkers were analyzed for their value at predicting flares among the 564 patients assigned to standard therapies plus placebo. Severe flare was defined according to the modified SLE Flare Index (SFI) and the development of any new British Isles Lupus Assessment Group (BILAG) A domain score. Severe and moderate flares were defined as development of one new BILAG A domain score or two new BILAG B domain scores.
Judging by these standards, the frequencies of flares over a year of treatment were as follows:
• SFI: 23.7%
• any new BILAG A domain score: 23.1%
• one new BILAG A domain score or two new BILAG B domain scores: 32.0%.
No demographic marker (e.g., race, age, sex, body mass index) proved predictive of flares. Clinically meaningful biomarkers of flares at 52 weeks included elevated anti–double-stranded DNA (anti-dsDNA) ≥30 IU/ml and B lymphocyte Stimulator (BLyS) >0.5ng/ml, with low C3 (<900 mg/L) being an independent predictor.
In the multivariate analysis, anti-dsDNA titer >200 IU/ml and renal involvement as judged by the SELENA-SLEDAI score independenty predicted severe flares as defined by any of these measures. But no class of conventional SLE treatment was more likely than another to be associated with flares.