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

被引:526
|
作者
Furie, Richard [1 ]
Rovin, Brad H. [2 ]
Houssiau, Frederic [3 ,4 ]
Malvar, Ana [5 ]
Teng, Y. K. Onno [6 ]
Contreras, Gabriel [7 ]
Amoura, Zahir [8 ,9 ]
Yu, Xueqing [10 ,11 ]
Mok, Chi-Chiu [12 ]
Santiago, Mittermayer B. [13 ]
Saxena, Amit [14 ]
Green, Yulia [15 ]
Ji, Beulah [15 ]
Kleoudis, Christi [16 ]
Burriss, Susan W. [17 ]
Barnett, Carly [17 ]
Roth, David A. [17 ]
机构
[1] Donald & Barbara Zucker Sch Med Hofstra Northwell, Div Rheumatol, Northwell Hlth, 865 Northern Blvd,Suite 302, Great Neck, NY 11021 USA
[2] Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA
[3] Catholic Univ Louvain, Pole Pathol Rhumatism Inflammatoires & Syst, Inst Rech Expt & Clin, Brussels, Belgium
[4] Clin Univ St Luc, Serv Rhumatol, Brussels, Belgium
[5] Org Med Invest, Buenos Aires, DF, Argentina
[6] Leiden Univ, Med Ctr, Dept Internal Med, Nephrol Sect, Leiden, Netherlands
[7] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol,Div Hypertens, Miami, FL 33136 USA
[8] Sorbonne Univ, INSERM, Unite 1135, Paris, France
[9] Sorbonne Univ, Hop Pitie Salpetriere, Assistance Publ Hop Paris,Ctr Reference Natl Lupu, Inst Endocrinol Malad Metab & Med Interne,Serv Me, Paris, France
[10] Guangdong Prov Peoples Hosp, Dept Nephrol, Guangzhou, Peoples R China
[11] Guangdong Acad Med Sci, Guangzhou, Peoples R China
[12] Tuen Mun Hosp, Dept Med, Hong Kong, Peoples R China
[13] Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil
[14] NYU, Sch Med, Div Rheumatol, New York, NY USA
[15] GlaxoSmithKline, Stockley Pk, Uxbridge, Middx, England
[16] Parexel, Durham, NC USA
[17] GlaxoSmithKline, Collegeville, PA USA
来源
NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 383卷 / 12期
关键词
MYCOPHENOLATE-MOFETIL; RENAL OUTCOMES; AZATHIOPRINE; DEFINITIONS; GUIDELINES; MANAGEMENT; ABATACEPT; EFFICACY; THERAPY; SAFETY;
D O I
10.1056/NEJMoa2001180
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundIn 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. MethodsIn 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 m(2) 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 <greater than or equal to>90 ml per minute per 1.73 m(2), and no use of rescue therapy). The time to a renal-related event or death was assessed. ResultsA 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. ConclusionsIn 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.) This phase 3 multicenter, randomized, double-blind, placebo-controlled 2-year trial compared the efficacy and safety of intravenous belimumab with those of placebo, plus standard therapy, in patients with active lupus nephritis. More patients who received belimumab had a primary efficacy renal response than those who received placebo.
引用
收藏
页码:1117 / 1128
页数:12
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