Objectives To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets.
Methods The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus stand SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect.
Results Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA–SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA–SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits reging severe flares, corticosteroid use and health-related quality of life.
Conclusions These findings suggest that belimumab has greater therapeutic benefit than stand therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline.
ClinicalTrials.gov identifiers NCT00424476 and NCT00410384
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Funding This study was funded by Human Genome Sciences and GlaxoSmithKline.
Ethics approval Ethics approval was granted by the institutional review bos at every clinical study site.
Competing interests RFvV has received consultancy fees and honoraria from Human Genome Sciences and GlaxoSmithKline. MAP and RC have received payment for bo membership and consultancy from Human Genome Sciences and GlaxoSmithKline. DAR, BNJ and CSK are employed by and own stock in GlaxoSmithKline. ZJZ and WF are employed by and own stock in Human Genome Sciences.
Provenance and peer review Not commissioned; externally peer reviewed.