Belimumab With MMF Attenuates eGFR Decline in Lupus Nephritis

Belimumab added to mycophenolate mofetil (MMF) standard therapy was associated with substantially less decline in estimated glomerular filtration rate (eGFR) and greater improvements in proteinuria and biomarkers compared with placebo over 2 years in people with lupus nephritis, according to a post hoc analysis of the BLISS-LN phase 3 trial presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdom.

RheumatologyLive spoke with Richard A. Furie, MD, Marilyn and Barry Rubenstein Chair in Rheumatology, Chief of the Division of Rheumatology at Northwell Health, and Professor of Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, a co-author on the analysis. BLISS-LN (NCT01639339) was a 104-week phase 3 trial enrolling patients with ISN/RPS class III or IV ± V or pure class V lupus nephritis (LN) receiving either MMF or cyclophosphamide (CYC) as background therapy. To align the BLISS-LN population more closely with other B-cell therapy LN trials, investigators analyzed an MMF subgroup restricted to class III or IV ± V (excluding pure class V) receiving only MMF standard therapy — representing approximately 60% of the original cohort (belimumab, n = 135; placebo, n = 136).

The primary focus of this analysis was eGFR slope, assessed from month 6 to week 104 to allow sufficient time for treatment effect. Per data reported in the transcript, the eGFR slope in the belimumab group was −1.4 mL/min/1.73 m² per year compared with −6.6 mL/min/1.73 m² per year in the placebo arm — a difference Furie described as clinically meaningful given that healthy individuals lose approximately 1 mL/min/1.73 m² of GFR per year with normal aging. Accelerated nephron loss in the setting of LN represents a trajectory toward chronic kidney disease, and attenuation of that loss represents a meaningful treatment goal.

Additional outcomes in the MMF subgroup at week 104 favored belimumab over placebo across multiple measures. Urine protein-to-creatinine ratio (uPCR) <0.5 responder rates were greater with belimumab, with the MMF subgroup showing larger benefits than the BLISS-LN overall population on this endpoint. Improvements in eGFR change from baseline and in biomarkers — including anti-dsDNA, anti-C1q, C3, and C4 — were also greater with belimumab. Risk of kidney-related events or death through week 104 was lower in the belimumab arm. Results for endpoints other than uPCR response were consistent between the MMF subgroup and the overall BLISS-LN population. The authors note that data are descriptive and findings should be interpreted accordingly.

"The name of the game with any part of your body is to maintain integrity of that particular organ, especially the kidney," Furie said. "This speaks to eGFR slope — perhaps one day it will be a primary endpoint for our studies, just like it is in non-lupus nephritis conditions."

The authors note that design differences across LN trials make cross-study comparisons challenging, and that this analysis was undertaken in part to enable better alignment with other phase 3 LN trial populations. The ongoing OBSErve-LN observational study (NCT06527872) will provide further real-world kidney function maintenance data with belimumab.

Furie’s disclosures include GSK.

References

1. Rovin BH, Anders H-J, Bertsias G, et al. Kidney function preservation with belimumab in patients with lupus nephritis receiving MMF standard therapy in BLISS-LN: improved proteinuria, clinical outcomes and biomarkers for belimumab versus placebo [abstract AB1167]. Ann Rheum Dis. 2026;85(suppl 1):s2187. doi:annrheumdis-2026-eular.B.604

2. Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020;383(12):1117–1128. doi:10.1056/NEJMoa2001180