Real-World Studies Offers Insight into Belimumab in Lupus Nephritis at ERA 2025

A pair of real-world studies presented at 62nd European Renal Association (ERA 2025) Congress highlight the potential benefit of belimumab (Benlysta) use among patients with lupus nephritis.

Belimumab was approved for the management of lupus nephritis by the US Food and Drug Administration in 2020 based on data from the BLISS-LN trial. With the approval, the BLyS-specific inhibitor from GlaxoSmithKline became the first agent to be approved by the FDA for both systemic lupus and lupus nephritis.

In the BLISS-LN trial, belimumab met its primary endpoint demonstrating a statistically significant difference in achievement of Primary Efficacy Renal Response (PERR) at 104 weeks relative to placebo therapy when both were added to standard of care (43% vs 32%; Odds Ratio, 1.55; 95% CI, 1.04 to 2.32; P = .0311). Additional data from the trial indicated use was associated with a statistically significant difference in the achievement of Complete Renal Response and time to renal-related event or death.

Study 1

In the study presented at ERA 2025, investigators offered insight into an observational, cross-sectional, retrospective, single-center study of patients with systemic lupus erythematosus (SLE) who received treatment with belimumab. The study itself included 17 patients, but the ERA 2025 analysis focused on 10 patients among this cohort with lupus nephritis.

To evaluate the impact of belimumab use among these patients, investigators planned to assess changes in laboratory parameters for creatinine, proteinuria, and anti-dsDNA at baseline, 6 months, and 12 months.

The 10-patient cohort had a mean of 36 years (range, 21 to 57), mean time with belimumab was 16.9 (SD, 10.69) months, and 5 patients were still receiving treatment at the time of analysis. Investigators noted the criteria to start treatment with belimumab was serological activity associated with musculoskeletal and/or skin symptoms, and it was administered to 7 patients due to lupus nephritis.

Upon analysis, results indicated 5 patients with lupus nephritis had achieved complete renal response at 1 year.

Laboratory Outcomes Over 12 Months:

Serum Creatinine (mg/dL):

Baseline: 0.713 (SD, 0.166)

Month 6: 0.763 (SD, 0.189) mg/dL

Month 12: 0.783 (SD, 0.116) mg/dL
(P = .748)

Proteinuria (g/24h):

Baseline: 0.822 ± 0.567

Month 6: 1.027 ± 0.824

Month 12: 0.796 ± 0.557
(P = .725)

Anti-dsDNA (U/mL):

Baseline: 162.5 (SD, 60.4)

Month 6: 74.3 (SD, 65.3)

Month 12: 72.0 (SD, 54.8) (P = .093)

Investigators pointed out only 1 patient required rituximab as salvage therapy due to persistent proteinuria and another patient was switched to anifrolumab after developing severe skin symptoms despite renal and immunologic response on belimumab. Investigators noted a single case involved tacrolimus coadministration as a steroid-sparing approach. Additionally, investigators highlighted that no major safety concerns were reported.1

“Belimumab, together with the standard immunosuppressive treatment, was seen to be effective against the renal and systemic involvement in the patients in our series, in spite of the limitations caused by the low number of patients,” concluded investigators.1

Study 2

The second, larger study was conducted by investigators from Portugal and leveraged retrospective data from a real-world cohort of patients with lupus nephritis who received belimumab as add-on therapy to standard-of-care treatment.

The study included 19 patients with systemic lupus erythematosus (SLE). biopsy-confirmed lupus nephritis. Of these, 7 met criteria for class III, 11 met criteria for class IV, and 1 met criteria for class V. a Belimumab was initiated either for active LN (53%) or to manage extra-renal disease in patients with coexisting nephritis. Investigators assessed renal parameters, extra-renal symptom response, and treatment tolerability over a mean follow-up of 18 months.2

At belimumab initiation, mean serum creatinine was 0.88 (SD, 0.3) mg/dL and mean proteinuria was 350 (SD, 501) mg/day. By the end of 1 year, proteinuria had decreased to 88.9 (SD, 161) mg/day and by year 2, it fell to 44.2 (SD, 58.3) mg/day. Mean serum creatinine remained stable throughout follow-up.2

Among patients treated for active lupus nephritis, 7 of 8 achieved complete renal remission at one year, and 3 of 4 maintained remission at 2 years.2

Investigators pointed out most patients experienced improvement in complement levels and anti-dsDNA antibodies. Additionally, arthritis, fatigue, rash, and serositis improved in all but 1 patient. Investigators also noted safety data suggested belimumab was generally well tolerated, with 1 patient discontinuing treatment due to infection associated with high-dose glucocorticoids and another due to psychiatric side effects.2

“In our cohort belimumab was well tolerated and clinical and renal response were favorable, although the number of patients and their follow-up is still short to draw significant conclusions,” wrote investigators.

References:

1. GlaxoSmithKline. FDA approves GSK’s BENLYSTA as the first medicine for adult patients with active lupus nephritis in the US | GSK. www.gsk.com. Published December 17, 2020. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-benlysta-as-the-first-medicine-for-adult-patients-with-active-lupus-nephritis-in-the-us/

2. Tudero CR, Calleja CH, Arribas am, et al. Real-world outcomes of belimumab in systemic lupus erythematosus and lupus nephritis. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

3. Da Costa JO, Marchão N, Godinho I, et al. Belimumab use in patients with systemic erythematous lupus and lupus nephritis - cohort of a tertiary center. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.