Abstract
Abstract
Background and Aims
Lupus nephritis (LN) is the most common severe manifestation of systemic lupus erythematosus (SLE), occurring in up to 40% of patients (pts) with SLE over their disease course, and resulting in 10–20% of pts progressing to end-stage kidney disease.1-3 The BLISS-LN (GSK Study BEL114054; NCT01639339) study demonstrated that the addition of intravenous (IV) belimumab (BEL) to standard therapy (ST) in pts with active LN significantly improved renal responses over 2 years compared with ST alone.4 Here we present additional safety and efficacy data from the 6-month open-label (OL) extension phase of BLISS-LN.
Method
In this OL phase, eligible completers of the Phase 3 BLISS-LN study (those who received BEL or placebo [PBO] through Week 100 and completed Week 104 assessments) received BEL 10 mg/kg IV plus ST every 28 days for 24 weeks. Endpoints at OL Week 28 included: safety; Primary Efficacy Renal Response (PERR; defined as urine protein:creatinine ratio [uPCR] ≤0.7; eGFR no more than 20% below OL baseline value or ≥60 ml/min/1.73m2; no rescue therapy); Complete Renal Response (CRR; defined as uPCR <0.5; eGFR no more than 10% below OL baseline value or ≥90 ml/min/1.73m2; no rescue therapy); uPCR; eGFR; the proportion of pts with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score <4; Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI); and corticosteroid use. Analyses were based on observed data and summarised relative to the OL baseline (last available value measured prior to dosing on or before the date of the first OL treatment dose).
Results
Of 257 pts (57.4 % of pts in BLISS-LN double-blind [DB] study) screened and enrolled, 255 pts were treated (safety population: 123 pts switched from PBO to BEL; 132 pts remained on BEL). In total, 254 pts were included in the efficacy analyses (PBO to BEL: 122 pts; BEL to BEL: 132 pts). Mean (standard deviation) age was 35.9 (10.3) years.
In total, 3.5% of pts withdrew from the OL phase, mainly due to adverse events (AE; 2.0%). Overall, 168/255 (65.9%) pts experienced ≥1 AE (76/123 [61.8%] PBO to BEL pts; 92/132 [69.7%] BEL to BEL pts); 49/255 (19.2%) pts had ≥1 treatment-related AE (25/123 [20.3%] PBO to BEL pts; 24/132 [18.2% ] BEL to BEL pts); 15/255 (5.9%) pts had ≥1 serious AE (5/123 [4.1%] PBO to BEL pts; 10/132 [7.6%] BEL to BEL pts); and 1 death was reported in the PBO to BEL group.
The proportion of patients achieving PERR and CRR increased from OL baseline to OL Week 28 in both groups (Table). The median (interquartile range [IQR]) for uPCR and eGFR were maintained from OL baseline through to OL Week 28 (Table).
The proportion of SLEDAI score <4 responders in BEL to BEL group tended to increase from OL baseline to OL Week 28, and decrease in the PBO to BEL group (Table). SDI worsening (change >0) was experienced by 7 (2.9%) pts (4 [3.3%] PBO to BEL; 3 [2.5%] BEL to BEL) compared with OL baseline.
There was no appreciable change in the number of patients receiving average daily prednisone-equivalent doses of ≤5 mg or ≤7.5 mg from OL baseline to OL Week 28 (Table).
Conclusion
BEL was well tolerated as an add-on to ST, with no new safety signals. Efficacy among pts with LN randomised to BEL during the DB phase was maintained during the OL phase.
Study funding
GSK. Editorial assistance (GSK-funded): Olga Conn, PhD, Fishawack Indicia Ltd., part of Fishawack Health, UK.