A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
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DOI：
10.1002/art.24699
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发表时间：
2009-09-15
影响因子：
--
通讯作者：
Freimuth, William W.
中科院分区：
文献类型：
--
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.
目的：评价贝利单抗联合标准护理疗法(SOC)治疗活动期系统性红斑狼疮(SLE)的安全性、耐受性、生物活性和疗效。在一项为期52周的研究中，赛琳娜-SLEDAI评分为≥4的患者被随机分配到Belimumab(1，4，10 mg/kg)或安慰剂。共同的主要终点是：1)24周时Selena-SLEDAI评分的百分比变化；2)到第一次SLE发作的时间。治疗组和安慰剂组之间在两个主要终点都没有达到显著差异，也没有观察到剂量反应。Belimumab联合组的Selena-SLEDAI评分较基线下降19.5%，而安慰剂组为17.2%。联合贝利单抗组首次出现系统性红斑狼疮发作的中位时间为67天，而安慰剂组为83天。然而，贝利单抗治疗24-52周的首次系统性红斑狼疮发作的中位时间显著延长(154vs108d；P=0.0361)。在血清学活动性患者亚组(71.5%)中(抗核抗体≥1：80和/或抗ds-DNA≥30IU/mL)，Belimumab治疗52周时的疗效显著优于安慰剂组(−28.8%对−14.2%；P=0.0435)；PGA(−32.7%对−10.7%；P=0.0011)；SF-36 PCS(+3.0vs+1.2分；P=0.0410)。在52周时，Belimumab治疗导致63-71%的原始、激活的和浆细胞样CD20+B细胞耗尽，抗双链DNA滴度下降29.4%(P≤0.0017)。Belimumab组和安慰剂组的不良事件(AEs)和严重AEs的发生率相似。Belimumab具有生物活性和良好的耐受性。Belimumab对SLE疾病活动性或红斑点的减少作用不明显。然而，血清活动性SLE患者对belimumab治疗加SOC的反应明显好于单独使用SOC。
To assess the safety, tolerability, biological activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Patients with SELENA-SLEDAI score≥4 (N=449) were randomly assigned to belimumab (1, 4, 10 mg/kg) or placebo in a 52-week study. Co-primary endpoints were: 1) percentage change in the SELENA-SLEDAI score at week 24; 2) time to the first SLE flare. Significant differences between the treatment and placebo groups were not attained for either primary endpoint and no dose response was observed. Reduction in SELENA-SLEDAI score from baseline was 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24–52 was significantly longer with belimumab treatment (154 versus 108 days; P=0.0361). In the subgroup (71.5%) of serologically active patients (ANA ≥1:80 and/or anti-dsDNA ≥30 IU/mL), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI (−28.8% versus −14.2%; P=0.0435); PGA (−32.7% versus −10.7%; P=0.0011); and SF-36 PCS (+3.0 versus +1.2 points; P=0.0410). Treatment with belimumab resulted in 63–71% depletion of naive, activated, and plasmacytoid CD20+ B cells and a 29.4% reduction in anti-dsDNA titers (P ≤0.0017) by week 52. The rates of adverse events (AEs) and serious AEs were similar in the belimumab and placebo groups. Belimumab was biologically active and well tolerated. Belimumab effect on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than SOC alone.
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DOI：
10.1084/jem.20031330
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Connor BP;Raman VS;Erickson LD;Cook WJ;Weaver LK;Ahonen C;Lin LL;Mantchev GT;Bram RJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
4.9
作者：
Collins CE;Gavin AL;Migone TS;Hilbert DM;Nemazee D;Stohl W
通讯作者：
Stohl W
影响因子：
--
作者：
Baker, KP;Edwards, BM;Albert, VR
通讯作者：
Albert, VR
影响因子：
4.4
作者：
Jacob, Chaim O.;Pricop, Luminita;Stohl, William
通讯作者：
Stohl, William
影响因子：
2.6
作者：
Petri, M;Buyon, J;Kim, M
通讯作者：
Kim, M