Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab
Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab
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DOI：
10.1056/nejmoa1614062
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发表时间：
2017-04-20
影响因子：
158.5
通讯作者：
Yunis, Carla
中科院分区：
文献类型：
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作者：
Ridker, Paul M.;Tardif, Jean-Claude;Yunis, Carla
Bococizumab是一种靶向前蛋白转化酶枯草杆菌蛋白酶-kexin 9型（PCSK 9）的人源化单克隆抗体，可降低低密度脂蛋白（LDL）胆固醇水平。然而，这种效果的变异性和持久性是undetermined. METHODS我们进行了6个平行的，多国降脂试验招募4300例高脂血症谁被随机分配到接受150毫克的bococizumab或安慰剂皮下注射，每2周，谁被随访长达12个月，96%的接受他汀类药物治疗的时间登记。根据在治疗期间检测到的抗药抗体的存在或不存在，对患者随时间的脂质变化进行评估。在12周时，接受bococizumab的患者的LDL胆固醇水平从基线降低了54.2%，相比之下，接受安慰剂的患者增加了1.0%（绝对组间差异，-55.2个百分点）。在总胆固醇、非高密度脂蛋白胆固醇、载脂蛋白B和脂蛋白（a）方面也观察到显著的组间差异（P
BACKGROUNDBococizumab, a humanized monoclonal antibody targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), reduces levels of low-density lipoprotein (LDL) cholesterol. However, the variability and durability of this effect are uncertain.METHODSWe conducted six parallel, multinational lipid-lowering trials enrolling 4300 patients with hyperlipidemia who were randomly assigned to receive 150 mg of bococizumab or placebo subcutaneously every 2 weeks and who were followed for up to 12 months; 96% were receiving statin therapy at the time of enrollment. The patients were assessed for lipid changes over time, stratified according to the presence or absence of antidrug antibodies detected during the treatment period.RESULTSAt 12 weeks, patients who received bococizumab had a reduction of 54.2% in the LDL cholesterol level from baseline, as compared with an increase of 1.0% among those who received placebo (absolute between-group difference, -55.2 percentage points). Significant between-group differences were also observed in total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (P