Belimumab Plus Standard Therapy Improves Renal Outcomes in Patients With Active Lupus Nephritis

The addition of belimumab to standard therapy is associated with improved renal outcomes, systemic lupus erythematosus (SLE) disease activity, and biomarker levels in patients with active lupus nephritis, according to study results presented at the American College of Rheumatology (ACR) Convergence 2020, held virtually from November 5 to 9, 2020.

The current phase 3, double-blind, placebo-controlled study (ClinicalTrials.gov Identifier: NCT01639339) included adults with SLE and active lupus nephritis who were randomly assigned to receive monthly intravenous belimumab 10 mg/kg or monthly intravenous placebo, with standard therapy. The outcome of interest was Primary Efficacy Renal Response (PERR) at week 104, defined by protein-creatinine ratio (uPCR) of 0.7 or less; estimated glomerular filtration rate (eGFR) not less than 20% below preflare value or 60 mL/min/1.73m² or greater; and no rescue therapy. Investigators also assessed the percentage of patients with Complete Renal Response (CRR) at week 104, defined by uPCR less than 0.5 and eGFR no less than 10% below preflare level or 90 mL/min/1.73m² or greater. Biomarker levels and adverse events were monitored throughout the study.

The study cohort included 448 patients, among whom 223 received placebo and 223 received belimumab. A significantly greater proportion of the belimumab vs placebo group achieved PERR at week 52 (46.6% vs 35.4%; P =.025) and week 104 (43.0% vs 32.3%; P =.031). The CRR at week 104 was also more common in the belimumab vs placebo group (30.0% vs 19.7%; P =.017). The percentage of patients achieving PERR and CRR at weeks 52 and 104 remained higher with belimumab across subgroups defined by lupus nephritis severity. The only exception was among patients with class 5 lupus nephritis; in this group, belimumab vs placebo was associated with nominally higher odds of PERR and CRR at week 104, though the difference was not significant (PERR, 44.4% vs 33.3%; CRR, 36.1% vs 27.8%, respectively). 

In patients with baseline autoantibodies, improvements were more significant with belimumab compared to placebo. At week 104, median percent change in baseline anti-dsDNA was -74.2 (interquartile range [IQR], -85.1 to -49.5) in patients who received belimumab compared with -36.6 (IQR, -69.7 to 28.6) in those who received placebo. Median percent change in anticomplement component 1q at week 104 was also greater with belimumab vs placebo (-73.2 [-84.1 to -59.0] vs -57.9 [-76.1 to -33.2], respectively). Among patients with low baseline complement levels, median percent change from baseline in C3 and C4 was greater with belimumab vs placebo.

Adverse events were reported by 95.5% and 94.2% of the belimumab and placebo groups, respectively. Overall, 12.9% of patients in each group discontinued treatment due to adverse events. Serious adverse events were reported by 25.9% of the belimumab group and 29.9% of the placebo group. The most common serious adverse events in the belimumab and placebo group were infections and infestations (13.8% and 17.0%, respectively). Adverse events leading to death (due to infections) were observed in 1.8% and 1.3% of the belimumab and placebo groups, respectively.

“In this large 2-year [lupus nephritis] study, compared with [standard treatment] alone, [belimumab] plus standard care improved renal outcomes, overall SLE disease activity, and biomarker levels, while reducing steroid use,” the investigators wrote. The belimumab safety profile was comparable to that of placebo, supporting the long-term safety of belimumab.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Furie R, Rovin B, Houssiau F, et al. Effects of belimumab on renal outcomes, overall SLE control and biomarkers: findings from a phase 3, randomized, placebo-controlled 104-week study in patients with active lupus nephritis. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 1441.