The Sterling Research Group, Cincinnati, OH, USA.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
J Clin Lipidol. 2020 Sep-Oct;14(5):707-719. doi: 10.1016/j.jacl.2020.07.009. Epub 2020 Jul 25.
The ODYSSEY CHOICE I study (NCT01926782) evaluated alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia receiving maximally tolerated statin or no statin.
The objective of the study was to assess the relationship between alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein cholesterol (LDL-C) concentrations with the CHOICE I alirocumab dosing regimen.
This analysis included 803 patients (547 statin-treated, 256 without statin) who were randomized to alirocumab 300 mg Q4W, alirocumab 75 mg every 2 weeks (Q2W), or placebo. 300 mg Q4W and 75 mg Q2W doses were adjusted to 150 mg Q2W at Week 12 if Week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline.
Most patients remained on 300 mg Q4W without dose adjustment as they achieved study-defined LDL-C goals at Week 8 (statin-treated: 80.7%; no statin: 85.3%). LDL-C was reduced by 60.5%-71.9% over Weeks 20-24 in patients on 300 mg Q4W and 57.2%-63.0% in patients with dose adjustment from 300 mg Q4W to 150 mg Q2W. Statin-treated patients had higher cardiovascular risk as well as higher free PCSK9 and lower alirocumab concentrations (vs no statin), suggesting increased target-mediated clearance. Regardless of statin status, the most common adverse events in alirocumab-treated patients were injection-site reaction and headache.
Data provide further insight on alirocumab's mode of action in terms of relationship between alirocumab, PCSK9, and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions.
ODYSSEY CHOICE I 研究（NCT01926782）评估了在接受最大耐受他汀类药物或未接受他汀类药物治疗的高胆固醇血症患者中，每 4 周（Q4W）给予 300mg 阿利西尤单抗的疗效。
本研究的目的是评估阿利西尤单抗、前蛋白转化酶枯草溶菌素/糜蛋白酶 9（PCSK9）和低密度脂蛋白胆固醇（LDL-C）浓度与 CHOICE I 阿利西尤单抗给药方案之间的关系。
该分析纳入了 803 例患者（547 例接受他汀类药物治疗，256 例未接受他汀类药物治疗），随机分为阿利西尤单抗 300mg Q4W、阿利西尤单抗 75mg Q2W 或安慰剂组。如果第 8 周 LDL-C＞70 或＞100mg/dL（根据心血管风险），或 LDL-C 降幅＜基线值的 30%，则第 12 周将 300mg Q4W 和 75mg Q2W 剂量调整为 150mg Q2W。
大多数患者在第 8 周达到研究定义的 LDL-C 目标后（接受他汀类药物治疗的患者：80.7%；未接受他汀类药物治疗的患者：85.3%），继续接受 300mg Q4W 治疗而无需调整剂量。在接受 300mg Q4W 治疗的患者中，LDL-C 在第 20-24 周降低了 60.5%-71.9%，在剂量从 300mg Q4W 调整为 150mg Q2W 的患者中降低了 57.2%-63.0%。接受他汀类药物治疗的患者具有更高的心血管风险，以及更高的游离 PCSK9 和更低的阿利西尤单抗浓度（与未接受他汀类药物治疗的患者相比），这表明存在更大的靶向清除作用。无论他汀类药物治疗状态如何，阿利西尤单抗治疗患者最常见的不良事件为注射部位反应和头痛。
本研究提供了关于阿利西尤单抗作用模式的进一步见解，包括阿利西尤单抗、PCSK9 和 LDL-C 之间的关系以及疾病严重程度，并支持将阿利西尤单抗 300mg Q4W 作为一种有效的治疗方案，以实现有临床意义的 LDL-C 降低。
