Insights from the BLISS-LN Phase 3 study of biomarker associations with kidney response to belimumab in lupus nephritis.

Abstract

This study evaluated the effects of belimumab versus placebo on biomarker responses and identified predictive biomarkers for kidney response to belimumab in patients with lupus nephritis (LN) receiving different standard therapies. BLISS-LN was a Phase 3 study (NCT01639339) of adults with active LN randomized to intravenous belimumab 10 mg/kg or placebo plus standard therapy (cyclophosphamide [CYC] or mycophenolate mofetil [MMF] as initial therapy followed by azathioprine or MMF). Absolute and percentage changes from baseline in immunoglobulins, anti-dsDNA and anti-C1q antibodies, C3 and C4, CD19⁺ B cells and subsets were assessed through Week 104. Post hoc logistic regression models assessed the association of baseline biomarker levels, and of early changes in biomarkers, with kidney response to belimumab in the overall population at Week 104. Of 446 patients (belimumab: 59 received CYC, 164 received MMF; placebo: 59 received CYC, 164 received MMF), approximately 50-60% had data on treatment at Week 104. At Week 104, numerically greater percentage reductions in IgA, IgM and anti-dsDNA antibodies and plasmablasts, and greater increases in C3 and C4 levels, were observed with belimumab versus placebo. Overall, belimumab reduced total CD19⁺ B cells and naïve B cells versus placebo. These results were generally consistent in the overall population and within each induction group. Predictors of kidney response observed in belimumab-treated patients included high baseline levels of IgA, anti-C1q antibodies and naïve B cells, low baseline plasmablasts and early decreases from baseline in levels of IgA, IgM and urinary protein to creatinine ratio. Similar effects of belimumab on biomarker outcomes were observed within the induction groups. Baseline biomarkers and early changes in biomarkers associated with kidney response to belimumab in LN were identified.