Efficacy and Safety of Belimumab in Patients With Lupus Nephritis: Subgroup Analyses of a Phase 3 Randomized Trial in the East Asian Population.

RATIONALE & OBJECTIVE: Belimumab improved kidney outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the United States and the European Union. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup. STUDY DESIGN: Prespecified subgroup analysis of BLISS-LN, a phase 3, placebo-controlled, randomized 104-week trial. SETTING & PARTICIPANTS: Adults with biopsy-proven, active LN were randomized (1:1) to belimumab or placebo, plus standard therapy. INTERVENTION: Patients were administered intravenous belimumab 10mg/kg, or placebo, plus standard therapy (oral glucocorticoids and either cyclophosphamide for induction followed by azathioprine for maintenance, or mycophenolate mofetil for both induction and maintenance). At the investigator's discretion, 1-3 intravenous pulses of methylprednisolone, 500-1,000mg each, could be administered during induction. OUTCOMES: The primary end point was primary efficacy renal response (PERR; ie, urinary protein-creatinine ratio≤0.7g/g, estimated glomerular filtration rate no more than 20% below preflare value or≥60mL/min/1.73m2, and no treatment failure) at week 104. Key secondary end points included complete renal response (CRR; urinary protein-creatinine ratio<0.5g/g, estimated glomerular filtration rate no more than 10% below preflare value or≥90mL/min/1.73m2, and no treatment failure) at week 104; PERR at week 52; time to kidney-related event or death; and safety. ANALYTICAL APPROACH: PERR and CRR were analyzed using a logistic regression model, and time to a kidney-related event or death was analyzed using a Cox proportional hazards regression model. RESULTS: 142 patients from mainland China, Hong Kong, South Korea, and Taiwan were included (belimumab, n=74; placebo, n=68). At week 104, more belimumab than placebo patients achieved PERR (53% vs 37%; OR, 1.76 [95% CI, 0.88-3.51]) and CRR (35% vs 25%; OR, 1.73 [95% CI, 0.80-3.74]). At week 52, more belimumab than placebo patients achieved PERR (62% vs 37%; OR, 2.74 [95% CI, 1.33-5.64]). Belimumab reduced the risk of a kidney-related event or death compared with placebo at any time (HR, 0.37 [95% CI, 0.15-0.91]). Safety was similar across treatment groups. LIMITATIONS: Small sample size and lack of formal significance testing. CONCLUSIONS: Safety and efficacy profiles were consistent with BLISS-LN overall population, supporting benefits of belimumab treatment in the East Asian subgroup with LN. FUNDING: This study was funded by GSK (GSK study no. BEL114054). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01639339.

Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study.

BACKGROUND AND OBJECTIVES: In the BLISS-LN study, belimumab improved kidney outcomes in adult patients with active lupus nephritis. This 28-week open-label extension of BLISS-LN assessed belimumab's safety and efficacy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eligible patients completing BLISS-LN received monthly intravenous belimumab 10 mg/kg plus standard therapy. End points included safety, open-label week 28 primary efficacy renal response (urine protein-creatinine ratio [UPCR] ≤0.7, eGFR no more than 20% below open-label baseline value or ≥60 ml/min per 1.73 m2, no prohibited medications) and complete renal response (UPCR <0.5, eGFR no more than 10% below open-label baseline value or ≥90 ml/min per 1.73 m2, no prohibited medications), and UPCR and eGFR by visit. Responses were also analyzed post hoc using the double-blind phase criteria. RESULTS: Of 257 enrolled patients, 255 were treated (safety population: n=123 switched from placebo-to-belimumab; n=132 remained on belimumab); 245 (97%) patients completed the study. Adverse events and serious adverse events were experienced by 62% and 4% of placebo-to-belimumab patients, respectively, and by 70% and 8% of belimumab-to-belimumab patients, respectively. One death occurred in the placebo-to-belimumab group. From open-label baseline to week 28, increases occurred in the proportions of patients achieving primary efficacy renal response (placebo-to-belimumab: from 60% to 67%; belimumab-to-belimumab: from 70% to 75%) and complete renal response (placebo-to-belimumab: from 36% to 48%; belimumab-to-belimumab: from 48% to 62%). Based on double-blind phase criteria, changes also occurred in the proportions achieving primary efficacy renal response (placebo-to-belimumab: from 54% to 53%; belimumab-to-belimumab: from 66% to 52%) and complete renal response (placebo-to-belimumab: from 34% to 35%; belimumab-to-belimumab: from 46% to 41%). The seeming decrease in response rates in the belimumab-to-belimumab groups was attributed to discontinuations/administration of glucocorticoids for non-SLE reasons as opposed to nephritis. Median UPCR and eGFR values were similar at open-label baseline and week 28. CONCLUSIONS: No new safety signals were identified, and efficacy was generally maintained throughout the open-label phase. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: BLISS-LN, NCT01639339.

Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison.

OBJECTIVE: To assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE). METHODS: We performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score; anti-dsDNA/C3/C4 levels); Week 52 SRI-6 response rate; and time to first severe flare (SELENA-SLEDAI Flare Index) over 52 weeks. Safety data were compared for all aforementioned studies along with adult LBSL02 (phase II) and BLISS-SC (phase III). RESULTS: SRI-4 response rates were similar across the paediatric and adult studies; more belimumab-treated patients achieved SRI-4 responses versus placebo (PLUTO: 52.8% vs 43.6%; BLISS-52: 57.6% vs 43.6%; BLISS-76: 43.2% vs 33.8%; BLISS-NEA: 53.8% vs 40.1%; EMBRACE: 48.7% vs 41.6%). Across all studies, SRI-4 response rates were generally greater in patients with baseline SELENA-SLEDAI scores ≥10 than in patients with baseline SELENA-SLEDAI scores ≤9. A similar proportion of belimumab-treated patients achieved SRI-6 across all studies (PLUTO: 41.2%; BLISS-52: 46.2%; BLISS-76: 33.1%; BLISS-NEA: 43.9%; EMBRACE: 37.5%). Belimumab reduced the risk of severe flare versus placebo in all studies. The incidence of adverse events was similar across all studies. CONCLUSIONS: These analyses demonstrate consistent efficacy and safety of belimumab plus standard therapy across paediatric and adult patients with SLE. TRIAL REGISTRATION NUMBERS: PLUTO (NCT01649765); BLISS-52 (NCT00424476); BLISS-76 (NCT00410384); BLISS-NEA (NCT01345253); EMBRACE (NCT01632241); BLISS-SC (NCT01484496); and LBSL02 (NCT00071487).