Deep clinical renal response in lupus nephritis treated with belimumab: a real-world cohort study

Abstract Objectives Lupus nephritis (LN) often progresses despite therapy, and current complete renal response (CRR) definitions tolerate residual proteinuria deemed suboptimal in other glomerulopathies. Belimumab, the first biologic approved for active LN, may enable deeper remission, but its real-world effectiveness is unknown. Methods We retrospectively studied a single-centre cohort of biopsy-proven LN receiving add-on belimumab (2015–2025), with follow-up to 24 months and a paired-biopsy subgroup. We explored a study-specific stringent composite endpoint, deep clinical renal response (DCRR): urine protein-to-creatinine ratio (uPCR) <200 mg/g, absence of active glomerular haematuria and stable renal function, benchmarked against conventional CRR (uPCR <500 mg/g, stable renal function). Results Of 51 patients, 43 not in CRR at initiation were analysed. DCRR was achieved by 38.5% at 12 and 53.8% at 24 months, versus 66.7% and 76.9% for CRR, in available-case analysis; deep responses accrued gradually (median 17.7 vs 7.5 months), still increasing during the second year. Baseline uPCR was the only variable consistently associated with 12-month response. Renal response occurred alongside improvements in systemic activity, serological markers, and glucocorticoid exposure (SLEDAI-2K 13 to 2; anti-dsDNA 205 to 54 IU/mL and glucocorticoid reduction in 72%). In eight paired biopsies, activity index fell from 5.5 to 2 (p = 0.016) with attenuated glomerular C3 deposition (3+ to 1+, p = 0.031), whereas chronicity indices rose; these findings are exploratory given the small, uncontrolled sample. Conclusion Deep renal response, accompanied by regression of histological activity, appears achievable in a growing proportion of patients. However, its impact on long-term renal protection remains to be established.