A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus.
A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus.
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DOI：
10.1002/art.30613
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发表时间：
2011-12
影响因子：
--
通讯作者：
van Vollenhoven, Ronald F.
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文献类型：
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作者：
Furie, Richard;Petri, Michelle;Zamani, Omid;Cervera, Ricard;Wallace, Daniel J.;Tegzova, Dana;Sanchez-Guerrero, Jorge;Schwarting, Andreas;Merrill, Joan T.;Chatham, W. Winn;Stohl, William;Ginzler, Ellen M.;Hough, Douglas R.;Zhong, Z. John;Freimuth, William;van Vollenhoven, Ronald F.
评估B淋巴细胞刺激因子抑制剂贝利木单抗/标准治疗（SOC）与安慰剂/SOC治疗活动性系统性红斑狼疮（SLE）的疗效/安全性。在一项多中心、随机、对照、III期试验中，819例抗核抗体或抗dsDNA阳性SLE患者（国家评估-SLE疾病活动指数（SELENA-SLEDAI）≥ 6）随机（1：1：1比例）接受静脉注射贝利木单抗1或10 mg/kg或安慰剂，第0、14和28天，然后每28天一次，持续72周。主要疗效分析：第52周时的SLE应答者指数（SRI）（SELENA-SLEDAI降低≥ 4分;无新的不列颠群岛狼疮评估A组和< 2个新的B器官领域评分;医生总体评估无恶化）。贝利木单抗10 mg/kg + SOC符合主要疗效终点：第52周时的SRI应答显著高于安慰剂（43.2% vs 33.5%; P = 0.017）;贝利木单抗1 mg/kg的应答率为40.6%（P = 0.089）。第76周缓解率：安慰剂组、贝利木单抗1和10 mg/kg组分别为32.4%、39.1%和38.5%。在评价较高的SELENA-SLEDAI阈值的事后敏感性分析中，贝利木单抗10 mg/kg在第52/76周获得了更好的区分。贝利木单抗1 mg/kg（34%; P = 0.023）和10 mg/kg（23%; P = 0.13）组76周内重度SELENA-SLEDAI发作的风险降低。严重和重度不良事件，包括感染、实验室检查异常、恶性肿瘤和死亡，在各组之间相当。贝利木单抗联合SOC显著改善了SRI缓解率，降低了SLE疾病活动度和严重发作，并且在SLE中总体耐受良好。
To assess the efficacy/safety of the B-lymphocyte stimulator inhibitor belimumab/standard-of-care (SOC) versus placebo/SOC in active systemic lupus erythematosus (SLE). In a multicenter, randomized, controlled, phase 3 trial, 819 antinuclear antibody- or anti-dsDNA-positive SLE patients with Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) ≥ 6 were randomized (1:1:1 ratio) to receive intravenous belimumab 1 or 10 mg/kg, or placebo on days 0, 14, and 28, and then every 28 days for 72 weeks. Primary efficacy analyses: SLE Responder Index (SRI) at week 52 (≥ 4-point reduction in SELENA-SLEDAI; no new British Isles Lupus Assessment Group A and < 2 new B organ domain scores; no worsening in Physician’s Global Assessment). Belimumab 10 mg/kg plus SOC met the primary efficacy endpoint: significantly greater SRI response at week 52 than placebo (43.2% versus 33.5%; P = 0.017); the rate with belimumab 1 mg/kg was 40.6% (P = 0.089). Week-76 response rates: 32.4%, 39.1%, and 38.5% with placebo, and belimumab 1 and 10 mg/kg, respectively. In post-hoc sensitivity analyses evaluating higher SELENA-SLEDAI thresholds, belimumab 10 mg/kg achieved better discrimination at weeks 52/76. Risk of severe SELENA-SLEDAI flares over 76 weeks was reduced with belimumab 1 mg/kg (34%; P = 0.023) and 10 mg/kg (23%; P = 0.13). Serious and severe adverse events including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. Belimumab plus SOC significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well-tolerated in SLE.
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影响因子：
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作者：
Petri, Michelle;Stohl, William;Freimuth, William
通讯作者：
Freimuth, William
影响因子：
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作者：
Wallace, Daniel J.;Stohl, William;Furie, Richard A.;Lisse, Jeffrey R.;McKay, James D.;Merrill, Joan T.;Petri, Michelle A.;Ginzler, Ellen M.;Chatham, W. Winn;McCune, W. Joseph;Fernandez, Vivian;Chevrier, Marc R.;Zhong, Z. John;Freimuth, William W.
通讯作者：
Freimuth, William W.
影响因子：
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作者：
Jacobi, Annett M.;Huang, Weiqing;Wang, Tao;Freimuth, William;Sanz, Inaki;Furie, Richard;Mackay, Meggan;Aranow, Cynthia;Diamond, Betty;Davidson, Anne
通讯作者：
Davidson, Anne
影响因子：
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作者：
Bernatsky, S;Boivin, JF;Clarke, A
通讯作者：
Clarke, A
影响因子：
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作者：
Baker, KP;Edwards, BM;Albert, VR
通讯作者：
Albert, VR