Early belimumab accelerates renal response and reduces glucocorticoid exposure in lupus nephritis: a multicenter propensity-matched study

Objective: International guidelines recommend early combination of standard therapy with innovative agents in lupus nephritis (LN) to prevent kidney damage. Whether this accelerates renal response is unclear. We aimed to compare renal response trajectories, predictors, glucocorticoid (GC) burden in LN patients receiving early belimumab plus standard-of-care (SoC) vs SoC alone. Methods: Consecutive adult patients with biopsy-proven LN treated with belimumab plus SoC as initial therapy were enrolled from Italian lupus referral centers and compared with a historical SoC cohort (1990-2016). Data were collected at baseline and during follow-up. Propensity score matching based on baseline proteinuria, eGFR, standard initial treatment and histological class led to comparable groups. Complete renal response (CRR) was defined per 2019 EULAR/EDTA. Cox regression was used to assess predictors. Results: 91 belimumab patients were matched to 91 SoC patients. At 6 months, CRR was higher in the belimumab group (35.9% vs 16.5%, OR (95% CI): 2.81 (1.30-6.29), p= 0.005), while response rates at 12 months were similar (p= 0.87). Time-to-CRR was shorter with belimumab (5.64 (4.08-7.80) vs 7.92 (5.28-11.04) months, p< 0.01). At CRR, GC dose was lower in the belimumab group (5 [5-15] vs 15 [10-20] mg/day, p= 0.018). Independent predictors of earlier CRR were baseline proteinuria (hazard ratio (HR) per g/24h increase (95% CI): 0.89 (0.80-0.98), p= 0.019) and belimumab use (1.70 (1.11-2.62), p= 0.016). Conclusions: Early belimumab combination therapy accelerates CRR and reduces GC exposure. Achieving early CRR with lower GC is a key target to limit kidney and GC-related damage, supporting early belimumab integration in LN management.