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LSO-028 Predictors of de novo renal flares in systemic lupus erythematosus – time to revisit belimumab dose for extra-renal disease? Results from five phase III clinical trials of belimumab
  1. Ioannis Parodis1,2,
  2. Julius Lindblom1,
  3. Nurşen Çetrez1,
  4. Leonardo Palazzo1,
  5. Henri Ala1,
  6. Frédéric Houssiau3,
  7. Christopher Sjöwall4 and
  8. Brad Rovin5
  1. 1Department of Medicine Solna, Karolinska Institutet, Sweden
  2. 2Department of Rheumatology, Örebro University, Sweden
  3. 3Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Belgium
  4. 4Department of Biomedical and Clinical Sciences, Linköping University, Sweden
  5. 5Department of Internal Medicine, The Ohio State University College of Medicine, USA


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.

  • systemic lupus erythematosus
  • lupus nephritis
  • belimumab

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