Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis

N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180.


Background: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown.

Methods: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed.

Results: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials.

Conclusions: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN number, NCT01639339.).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Azathioprine / therapeutic use
  • Creatinine / urine
  • Cyclophosphamide / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Infusions, Intravenous
  • Intention to Treat Analysis
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / mortality
  • Male
  • Mycophenolic Acid / therapeutic use
  • Remission Induction


  • Antibodies, Monoclonal, Humanized
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • belimumab
  • Cyclophosphamide
  • Creatinine
  • Mycophenolic Acid
  • Azathioprine

Associated data