Belimumab plus standard therapy was more effective for the treatment of patients with lupus nephritis compared with standard therapy alone, according to the results of a 2-year randomized trial.
According to the study recently published in the New England Journal of Medicine, lupus nephritis affects 25% to 60% of patients with SLE and is the most common severe manifestation of SLE and a major cause of illness and death.
“The percentage of patients who have a renal response despite aggressive treatment remains unacceptably low, and in 10% to 30% of patients with lupus nephritis, this condition progresses to end-stage kidney disease,” Richard Furie, MD, from the division of rheumatology at Northwell Health and the Donald and Barbara Zucker School of Medicine at Hofstra–Northwell and colleagues wrote in the study. “This risk has remained unchanged during the past three decades.”
To compare the efficacy and safety of adding intravenous belimumab as compared with placebo, researchers conducted a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries.
Adults with biopsy-proven, active lupus nephritis were assigned 1:1 to receive intravenous belimumab or placebo in addition to standard therapy. A total of 448 patients were randomized evenly with 224 patients in each of the groups.
The primary endpoint of the study was primary efficacy renal response defined as urinary protein to creatinine ratio ≤0.7, an estimated glomerular filtration rate within 20% of the pre-flare value, or 60 mL/min/1.73m2 or greater, and no rescue therapy at 104 weeks. The major secondary end point was a complete renal response, defined as a urinary-protein-to-creatinine ratio of less and 0.5, an eGFR that was no worse than 10% below the pre-flare value or at least 90 mL per minute per 1.73 m2, and no use of rescue therapy.
According to the results of the study, a larger number of patients in the belimumab group had a primary efficacy renal response (43% vs. 32%; OR, 1.6; 95% CI, 1.0 to 2.3; P = .03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = .02) when compared to those in the placebo group.
Patients who received combined belimumab and standard therapy had a lower risk of a renal-related event or death when compared to patients who received a placebo (HR: 0.51; 95% CI, 0.34 to 0.77; P = .001).
“Despite aggressive treatment, approximately 60% of patients with lupus nephritis do not have complete remission, and these patients have poor long-term outcomes. Furthermore, 27% to 66% of patients with lupus nephritis that is in remission have subsequent flares,” the researchers wrote. “Thus, safer therapies that reduce kidney inflammation, prevent flares, and preserve kidney function are needed.”
Disclosure: Furie reports advisory board fees and travel support from GlaxoSmithKline, AbbVie, AstraZeneca (MedImmune), Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly & Co., EMD Serono, Equillium, Galápagos, Genentech, Glenmark Pharmaceuticals, Novartis, Reistone Biopharma, Sanofi, Takeda and Union Chimique Belge, as well as consulting fees from Alexion, Aurinia Pharmaceuticals, Daiichi Sankyo, Janssen Pharmaceuticals, Kezar Life Sciences, and MorphoSys.
Please see the study for a full list of author disclosures.