Background Each lupus nephritis (LN) flare causes nephron loss that equals a decade or more of reduction in renal function lifespan. Identification of readily available signals of imminent flare is therefore expected to improve prognosis. In light of observed cases of de novo LN during belimumab treatment, we evaluated predictors of de novo renal flare occurrence in patients with systemic lupus erythematosus (SLE) and no prior history of renal disease undergoing standard therapy (ST) with or without add-on belimumab in clinical trial settings.
Methods Data from five clinical trials of belimumab in SLE (BLISS-52 NCT00424476; BLISS-76 NCT00410384; BLISS-NEA NCT01345253; BLISS-SC NCT01484496; EMBRACE NCT01632241) were utilised. The study population comprised 1932 patients with a baseline renal British Isles Lupus Assessment Group (BILAG) score E. De novo renal flares were defined as a change from renal BILAG E to A or B within a 52-week follow-up. Predictors of renal flare occurrence were investigated using Cox regression analysis.
Results De novo renal flares were documented in 146 (7.6%) patients. In multivariable Cox regression analysis adjusting for age, sex, ethnicity, serum creatinine, and variables that differed significantly in univariable analysis, Asian ancestry was associated with imminent de novo renal flare (HR: 1.60; 95% CI: 1.03–2.49; p=0.036). Notably, use of belimumab 1 mg/kg by intravenous (IV) infusion yielded a nearly 3 times decreased hazard of renal flare (HR: 0.37; 95% CI: 0.20–0.68; p=0.001), whereas IV belimumab 10 mg/kg and belimumab 200 mg administered subcutaneously (SC) displayed no clear protection.
Conclusions Asian patients appeared particularly susceptible to new-onset renal involvement, corroborating the substantial vulnerability of Asian SLE populations to renal affliction. Discrepant results between low and high/approved belimumab doses warrant in-depth mechanistic exploration of underlying reasons e.g., potential effects of belimumab on B cell subsets that acquire regulatory properties.
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