A post hoc analysis of BLISS-LN found Belimumab plus mycophenolate mofetil improves kidney outcomes versus placebo plus mycophenolate mofetil in active lupus nephritis.

Abstract

Belimumab, approved for systemic lupus erythematosus (SLE) and lupus nephritis (LN) treatment, is a B-cell-modulating monoclonal antibody that selectively inhibits B-lymphocyte stimulator (BLyS) and downregulates autoreactive B-cells. Comparing belimumab's results from BLISS-LN (phase 3, NCT01639339) with other LN trial outcomes pose challenges because, unlike other trials, BLISS-LN included patients with pure class V LN (membranous) and patients receiving cyclophosphamide as standard therapy (ST). This post hoc analysis of BLISS-LN investigated kidney outcomes in patients with proliferative (class III or IV) or proliferative plus membranous LN (class III or IV with/without class V) treated with mycophenolate mofetil (MMF)-based ST to more closely align with those of other phase 3 LN trials and current practice. Only patients with active class III or IV LN with/without class V who received MMF ST in BLISS-LN were included. Kidney responses (complete renal response [CRR]; primary efficacy renal response [PERR]), urine protein to creatinine ratio (uPCR) under 0.5 g/g responders, estimated glomerular filtration rate (eGFR) slope, and changes from baseline in uPCR, eGFR, and biomarkers were assessed up to Week 104. Safety outcomes were assessed through Week 104. The MMF subgroup comprised 271 patients (60.5% of overall BLISS-LN population; with 135 receiving belimumab; 136 receiving placebo. Baseline demographics and characteristics were balanced. CRR treatment differences between belimumab and placebo were higher in the MMF subgroup (14.9%) versus the overall BLISS-LN population (10.3%). Treatment differences were greater for PERR, uPCR under 0.5 responders and eGFR slope with belimumab versus placebo in the MMF subgroup, and versus the overall population. Other endpoints showed a similar trend. Safety outcomes were consistent with belimumab's known safety profile. Fewer serious adverse events were reported for belimumab vs placebo in the MMF subgroup. The improvements in kidney outcomes with belimumab in patients with LN receiving MMF highlight the benefit of belimumab in a population more closely aligned with recent phase 3 LN trials and underlines kidney function preservation.