Belimumab plus standard therapy boosts renal outcomes, reduces steroids in lupus nephritis
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Adding belimumab to standard therapy improves renal outcomes, biomarker levels and overall disease activity among patients with lupus nephritis, according to a speaker at ACR Convergence 2020.
“Post-hoc analyses of the previous belimumab phase 3 studies showed improvements in renal parameters in the 15% of patients with systemic lupus who had baseline evidence of kidney involvement, with proteinuria or sediment,” Richard Furie, MD, chief of the division of rheumatology at Northwell Health, in New York, told attendees at the virtual meeting.
To examine to efficacy and safety of belimumab (Benlysta, GlaxoSmithKline) combined with standard therapy among patients with lupus nephritis, Furie and colleagues conducted the BLISS-LN trial, a phase 3, randomized, placebo-controlled, 104-week study. A total of 448 adults with systemic lupus erythematosus and biopsy-confirmed lupus nephritis were randomized 1-to-1 to receive either 10 mg/kg of intravenous belimumab or placebo alongside standard therapy. The researchers stratified the randomization by race and treatment strategy — high-dose corticosteroids plus either cyclophosphamide followed by azathioprine, or mycophenolate mofetil, followed by mycophenolate mofetil.
The primary endpoint was the Primary Efficacy Renal Response — defined as a urine protein-creatinine ratio of 0.7 or less, an estimated glomerular filtration rate of no worse than 20% below pre-flare value, or at least 60 ml/min/1.73m2, with no rescue therapy — at week 104. Key secondary responses included Complete Renal Response at week 104, Ordinal Renal Response at week 104, Primary Efficacy Renal Response at week 52, time to renal-related event or death.
Primary Efficacy Renal Response and Complete Renal Response rates at week 104 were assessed in subgroups, based on treatment regimens, lupus nephritis class and race. Additional week-104 assessments included time to first severe SLEDAI Flair Index flare, proportions of patients with a SLEDAI-S2K score of less than four and a prednisone dose of 7.5/5 mg per day or less, changes from baseline in biomarkers and safety. The efficacy analysis group included 223 participants, while safety was examined in 224 participants.
According to the researchers, the risk for a renal-related event or death was lower over the course of the study among patients who received belimumab compared with placebo (HR= 0.5; 95% CI, 0.3-0.8). In addition, the odds for Primary Efficacy Renal and Complete Renal responses at week 104 with belimumab were numerically greater than those for placebo for the listed subgroups, except pure class V lupus nephritis. However, in class V lupus nephritis, a numerically greater proportion of patients in the belimumab group, compared with placebo, achieved Primary Efficacy Renal Response — 44.4% compared with 33.3% — or Complete Renal Response — 36.1% compared with 27.8% — at week 52.
Among patients with baseline autoantibodies, the median percent changes from baseline, for belimumab compared with placebo, were –74.2 vs. –36.6 respectively, for anti-dsDNA, and –73.2 vs. –57.9, respectively, for anti-C1q. In patients with low baseline complement levels, median percent changes from baseline were 43.8 vs. 30, respectively, for C3, and 115.5 vs. 66.7, respectively, for C4.
Regarding safety, adverse events were reported in 95.5% of those in the belimumab group, compared with 94.2% of those who received a placebo. In all, 12.9% of participants in each group experienced at least one adverse event that resulted in treatment discontinuation. Serious adverse events were reported in 25.9% of those treated with belimumab and in 29.9% of the placebo group, with the most common being infections and infestations. In addition, 1.8% of those in the belimumab group, and 1.3% of the placebo group, developed on-treatment fatal adverse events, mainly due to infections.
“BLISS-LN, the largest lupus nephritis study performed to date, showed that the addition of belimumab to standard therapy, compared with standard therapy alone, resulted in improved renal outcomes, overall lupus disease activity, biomarkers and reduced steroid use, while maintaining an acceptable safety profile,” Furie said. “For further details, I direct you to the New England Journal of Medicine publication in September.”
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Furie R. Abstract 1441. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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