From the Division of Rheumatology, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, Great Neck, NY (R.F.); the Division of Nephrology, Ohio State University, Columbus (B.H.R.); Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, and Service de Rhumatologie, Cliniques Universitaires Saint-Luc - both in Brussels (F.H.); Organización Médica de Investigación, Buenos Aires (A.M.); the Department of Internal Medicine, Section of Nephrology, Leiden University Medical Center, Leiden, the Netherlands (Y.K.O.T.); the Division of Nephrology, Division of Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami (G.C.); Sorbonne Université, INSERM Unité 1135 (Z.A.), and Assistance Publique-Hôpitaux de Paris Sorbonne Université, Service de Médecine Interne 2, Institut Endocrinologie, Maladies Métaboliques et Médecine Interne, Centre de Référence National du Lupus et Syndrome des Antiphospholipides, Hôpital Pitié-Salpêtrière (Z.A.) - both in Paris; the Department of Nephrology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou (X.Y.), and the Department of Medicine, Tuen Mun Hospital, Hong Kong (C.C.M.) - both in China; Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (M.B.S.); the Division of Rheumatology, New York University School of Medicine, New York (A.S.); GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (Y.G., B.J.); Parexel, Durham, NC (C.K.); and GlaxoSmithKline, Collegeville, PA (S.W.B., C.B., D.A.R.).
N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180.
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.
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 m 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 m, and no use of rescue therapy). The time to a renal-related event or death was assessed.
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.
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.).
在患有活动性狼疮肾炎的成人中，贝鲁单抗静脉注射联合标准治疗（霉酚酸酯或环磷酰胺-硫唑嘌呤）与安慰剂相比的疗效和安全性尚不清楚。
在一项在 21 个国家的 107 个地点进行的、有 104 周随访的 3 期、多国、多中心、随机、双盲、安慰剂对照试验中，我们将活检证实的、有活动性狼疮肾炎的成人按照 1:1 的比例随机分配，接受贝鲁单抗（10mg/kg 体重）或匹配的安慰剂，同时接受标准治疗。第 104 周的主要终点是主要疗效性肾脏应答（尿蛋白/肌酐比值≤0.7，估计肾小球滤过率[eGFR]比肾脏发作前（预发作值）不下降超过 20%或≥60ml/min/1.73m2 且不使用挽救性治疗），主要次要终点是完全肾脏应答（尿蛋白/肌酐比值<0.5，eGFR 比预发作值不下降超过 10%或≥90ml/min/1.73m2 且不使用挽救性治疗）。评估肾脏相关事件或死亡的时间。
共有 448 名患者接受了随机分组（贝鲁单抗组 224 例，安慰剂组 224 例）。第 104 周时，贝鲁单抗组较安慰剂组有更多患者达到主要疗效性肾脏应答（43% vs. 32%；比值比，1.6；95%置信区间[CI]，1.0 至 2.3；P=0.03）和完全肾脏应答（30% vs. 20%；比值比，1.7；95%CI，1.1 至 2.7；P=0.02）。接受贝鲁单抗治疗的患者发生肾脏相关事件或死亡的风险低于接受安慰剂治疗的患者（风险比，0.51；95%CI，0.34 至 0.77；P=0.001）。贝鲁单抗的安全性与之前的试验一致。
在这项涉及活动性狼疮肾炎患者的试验中，接受贝鲁单抗联合标准治疗的患者比单独接受标准治疗的患者有更多的主要疗效性肾脏应答。（由葛兰素史克公司资助；BLISS-LN 临床试验.gov 编号，NCT01639339。）
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