Lipid Clinic, Oslo University Hospital, Aker Sykehus, Bygg 6, Trondheimsveien 235, Postboks 4959 Nydalen, 0424, Oslo, Norway.
Academic Medical Center, Amsterdam, The Netherlands.
Cardiovasc Drugs Ther. 2020 Aug;34(4):515-523. doi: 10.1007/s10557-020-06984-0.
During the alirocumab open-label extension study ODYSSEY OLE (open-label extension; NCT01954394), physicians could adjust alirocumab dosing for enrolled patients, who were diagnosed with heterozygous familial hypercholesterolemia (HeFH) and who had completed previous phase III clinical trials with alirocumab. This post hoc analysis evaluated the differences in physician-patient dosing decisions between the regions of Western Europe, Eastern Europe, North America, and the rest of the world (ROW).
Patients (n = 909) who received starting dose alirocumab 75 mg every 2 weeks (Q2W) during ODYSSEY OLE (patients from FH I, FH II, and LONG TERM parent studies) were included. Low-density lipoprotein cholesterol (LDL-C) levels were blinded until week 8; subsequently, LDL-C values were communicated to physicians. From week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible.
Mean LDL-C values used for the decision to increase dose from 75 to 150 mg Q2W were higher in Eastern Europe (3.7 mmol/L; 144.0 mg/dL) and ROW (3.8 mmol/L; 145.2 mg/dL) compared with Western Europe (3.1 mmol/L; 118.6 mg/dL) and North America (3.3 mmol/L; 126.6 mg/dL). Irrespective of region, the mean LDL-C at the time of decision to maintain at 75 mg Q2W was approximately 1.8 mmol/L (70 mg/dL). During ODYSSEY OLE (median treatment duration of 131.7 weeks), alirocumab was shown to have no unexpected long-term safety concerns.
In this OLE study, the observed variations in clinical treatment decisions suggest that physicians may perceive the severity of HeFH and/or the treatment of HeFH differently depending on their region.
在阿利西尤单抗开放标签扩展研究 ODYSSEY OLE（开放标签扩展；NCT01954394）中，医生可以根据已确诊为杂合子家族性高胆固醇血症（HeFH）并完成了阿利西尤单抗之前的 III 期临床试验的入组患者调整阿利西尤单抗的剂量。本事后分析评估了西欧、东欧、北美和世界其他地区（ROW）之间医生-患者剂量决策的差异。
纳入在 ODYSSEY OLE 中接受起始剂量阿利西尤单抗 75mg，每 2 周（Q2W）治疗的患者（n=909；来自 FH I、FH II 和 LONG TERM 母研究的患者）。低密度脂蛋白胆固醇（LDL-C）水平在第 8 周前处于盲态；此后，医生会获知 LDL-C 值。从第 12 周开始，可以将剂量从 75mg 增加到 Q2W 的 150mg，或者反之亦然。
用于决定将剂量从 75mg 增加到 Q2W 的 150mg 的平均 LDL-C 值在东欧（3.7mmol/L；144.0mg/dL）和 ROW（3.8mmol/L；145.2mg/dL）高于西欧（3.1mmol/L；118.6mg/dL）和北美（3.3mmol/L；126.6mg/dL）。无论区域如何，决定维持 75mg Q2W 时的平均 LDL-C 约为 1.8mmol/L（70mg/dL）。在 ODYSSEY OLE 期间（中位治疗时间为 131.7 周），阿利西尤单抗未显示出任何意外的长期安全性问题。
在这项 OLE 研究中，观察到的临床治疗决策变化表明，医生可能根据其所在地区不同，对 HeFH 的严重程度和/或 HeFH 的治疗方式有不同的看法。
