Real-world experience with belimumab in lupus nephritis: insights from the Spanish cohort

Abstract

OBJECTIVES: Belimumab has emerged as a therapeutic option for lupus nephritis (LN); however, real-world evidence on its effectiveness remains limited. This study aimed to evaluate the effectiveness and safety of belimumab and to identify renal and immunological predictors of response in Spanish patients with LN. METHODS: We conducted a retrospective, multicenter study including patients with biopsy-confirmed LN treated with belimumab between 2012 and 2024. Outcomes included primary efficacy renal response (PERR), complete renal response (CRR), changes in proteinuria, estimated glomerular filtration rate (eGFR), urinary sediment, histological parameters, and immunological serologic markers, including anti-double-stranded DNA antibodies (anti-dsDNA), complement components C3 and C4, and erythrocyte sedimentation rate(ESR). Renal flares were defined according to the BLISS-LN criteria. Data on disease activity (SLEDAI-2K), adverse events, and concomitant immunosuppressive therapies were also collected. RESULTS: The study included 202 patients, predominantly women (87.5%), with mainly proliferative LN (79.7%). At 6, 12, and 24 months, PERR was achieved in 70.7%, 71.1%, and 72.7% of patients, respectively, while CRR rates were 52.4%, 47.6%, and 49.1%. These outcomes were consistent with those reported in the BLISS-LN and BeRLiSS-LN trials. Early initiation of belimumab was associated with greater improvement in renal and immunological serologic markers. A ?50% reduction in anti-dsDNA levels at 12 months was associated with higher odds of achieving PERR (OR 3.91, 95%CI 1.00-15.30; p = 0.050). In a small subgroup undergoing repeat biopsy, histological activity index improved after treatment initiation. SLEDAI-2K score significantly decreased (p<0.001), accompanied by a low rate of renal flares. Prednisone and mycophenolate mofetil (MMF) doses decreased significantly during follow-up. Belimumab was well tolerated, with few discontinuations due to adverse events. CONCLUSIONS: Belimumab use was associated with maintenance or improvement of renal response in a real-world cohort of patients with LN. The apparent benefits of early initiation, together with the observed reductions in corticosteroid and MMF doses, the favorable safety profile, and the low rate of renal flares, suggest that belimumab may be an effective option both in early disease and for long-term management. Furthermore, a ?50% reduction in anti-dsDNA antibody titers may represent a useful prognostic biomarker of renal response in patients with predominantly proliferative LN treated with belimumab.