TY - JOUR
T1 - Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis
AU - Furie, Richard
AU - Rovin, Brad H.
AU - Houssiau, Frederic
AU - Malvar, Ana
AU - Teng, Y. K.Onno
AU - Contreras, Gabriel
AU - Amoura, Zahir
AU - Yu, Xueqing
AU - Mok, Chi Chiu
AU - Santiago, Mittermayer B.
AU - Saxena, Amit
AU - Green, Yulia
AU - Ji, Beulah
AU - Kleoudis, Christi
AU - Burriss, Susan W.
AU - Barnett, Carly
AU - Roth, David A.
N1 - Funding Information:
The sponsor (GlaxoSmithKline) — which contributed to the design of the trial, the collection, analysis, and interpretation of the data, and the decision to submit the manuscript for publication — supported the authors in the development of the manuscript. All the authors, including those employed by the sponsor, approved the content of the submitted manuscript. Medical writing support was funded by the sponsor. All the authors vouch for the accuracy and completeness of the data and the reporting of adverse events and for the fidelity of the trial to the protocol, available with the full text of this article at NEJM.org.
Publisher Copyright:
© 2020 Massachusetts Medical Society.
PY - 2020/9/17
Y1 - 2020/9/17
N2 - 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, placebocontrolled, 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 ClinicalTrials.gov number, NCT01639339.).
AB - 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, placebocontrolled, 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 ClinicalTrials.gov number, NCT01639339.).
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U2 - 10.1056/NEJMoa2001180
DO - 10.1056/NEJMoa2001180
M3 - Article
C2 - 32937045
AN - SCOPUS:85091129798
VL - 383
SP - 1117
EP - 1128
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 12
ER -