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506 Belimumab (BEL) improves renal outcomes in active Lupus Nephritis (LN): a phase 3 randomized, Placebo (PBO)-controlled trial
  1. Brad H Rovin1,
  2. Frédéric Houssiau2,
  3. Richard Furie3,
  4. Ana Malvar4,
  5. YK Onno Teng5,
  6. Gabriel Contreras6,
  7. Xueqing Yu7,
  8. Beulah Ji8,
  9. David Roth9,
  10. Christi Kleoudis10†,
  11. Susan Makowiak9,
  12. Anuradha Madan9,
  13. Jennifer Gilbride11 and
  14. Yulia Green8
  1. 1The Ohio State University, Columbus, OH, USA
  2. 2Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  3. 3Northwell Health, Great Neck, NY, USA
  4. 4Organizacion Medica de Investigacion, Buenos Aires, Argentina
  5. 5Leiden University Medical Center, Leiden, the Netherlands
  6. 6University of Miami Miller School of Medicine, Miami, FL, USA
  7. 7Guangdong Provincial People’s Hospital, Guangzhou, China
  8. 8GlaxoSmithKline, Stockley Park, Uxbridge, UK
  9. 9GlaxoSmithKline, Collegeville, PA, USA
  10. 10Parexel, Durham, NC, USA
  11. 11GlaxoSmithKline, Stevenage, UK
  12. †At the time of study


Background BEL is approved for patients (pts) with systemic lupus erythematosus (SLE). We evaluated intravenous (IV) BEL in active LN.

Methods This 104-week trial (GSK Study BEL114054; NCT01639339) randomized adults with active LN (class III, IV, and/or V) 1:1 to monthly BEL 10 mg/kg IV or PBO, plus standard therapy (ST) with high-dose corticosteroids + either cyclophosphamide (CyC) or mycophenolate mofetil (MMF) for induction at the investigator’s discretion. CyC was followed by azathioprine (AZA), and MMF by MMF maintenance. The primary endpoint was Primary Efficacy Renal Response (PERR = urine protein:creatinine ratio [uPCR] ≤0.7; estimated glomerular filtration rate [eGFR] no more than 20% below pre-flare value or ≥60 ml/min/1.73m2; no rescue therapy) at Week 104. Other endpoints were Complete Renal Response (CRR = uPCR <0.5; eGFR no more than 10% below pre-flare value or ≥90 ml/min/1.73 m2; no rescue therapy) at Week 104; time to renal event (end-stage kidney disease, doubling of serum creatinine, increased proteinuria and/or impaired renal function, renal disease-related treatment failure) or death. Endpoints were analyzed by ST regimen.

Results 224 pts were randomized to each arm. At Week 104, there were significantly more PERR and CRR responders on BEL vs PBO: (43.0% vs 32.3%, OR [95% CI] 1.6 [1.0, 2.3]; p=0.03) and (30.0% vs 19.7%, OR [95% CI] 1.7 [1.1, 2.7]; p=0.02), respectively. Risk of renal event or death was lower in BEL pts relative to PBO (HR [95% CI] 0.5 [0.3, 0.8]; p<0.01). Week 104 PERR response rates in pts on CyC/AZA were 33.9% with BEL and 27.1% with PBO, and 46.3% with BEL vs 34.1% with PBO in those on MMF. BEL reduced risk of renal event or death on background of CYC/AZA (HR [95% CI] 0.5 [0.2, 1.0]) and MMF (HR [95% CI] 0.5 [0.3, 0.8]) relative to PBO. Adverse events (AEs; ≥1) occurred in 95.5% of BEL and 94.2% of PBO pts, and 25.9% of BEL and 29.9% of PBO pts had ≥1 serious AE.

Conclusions The addition of BEL to commonly used ST for the treatment of LN significantly improved renal responses with no unexpected safety signals.


  1. Brad H Rovin, Frédéric Houssiau, Richard Furie, Ana Malvar, Y K Onno Teng, Gabriel Contreras, Xueqing Yu, Beulah Ji, David Roth, Christi Kleoudis, Susan Makowiak, Anuradha Madan, Jennifer Gilbride, Yulia Green. Belimumab (BEL) improves renal outcomes in active lupus nephritis (LN): a phase 3 randomized, placebo (PBO)-controlled trial. J Am Soc Nephrol. 2020;31:54.

Acknowledgments Abstract1 reprinted from ASN Kidney Week, held October 22–25, 2020. Reprinted by GSK on behalf of the original authors with their permission.

Funded by GSK. Editorial support: Paragon, UK (funded by GSK)

Trial Registration NCT0163933. GSK Study BEL114054

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