Department of Vascular Medicine, Academisch Medisch Centrum, Amsterdam, The Netherlands.
Faculty of Health Sciences, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
J Clin Lipidol. 2017 Nov-Dec;11(6):1448-1457. doi: 10.1016/j.jacl.2017.09.003. Epub 2017 Sep 22.
Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3).
The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials.
Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420 mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset of HeFH patients.
Four hundred forty HeFH patients from RUTHERFORD (n = 147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58% male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n = 151). The 48-week period was completed by 425 patients (96.6%). Eight patients discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared to parent study baseline, patients receiving evolocumab plus SOC experienced a mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No patient experienced an adverse event leading to permanent evolocumab discontinuation during the 1-year SOC-controlled period. Serious adverse event rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%).
Continued use of evolocumab added to SOC in patients with HeFH yields persistent and marked low-density lipoprotein cholesterol reductions during 48 weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well tolerated.
在杂合子家族性高胆固醇血症（HeFH）患者中，每周两次（Q2W）或每月一次（QM）给药的依洛尤单抗是安全有效的，这在两项为期 12 周的试验中得到了证实：杂合子家族性高胆固醇血症紊乱中用 PCSK9 抑制剂降低 LDL-C（RUTHERFORD；2 期）和 RUTHERFORD-2（3 期）。
本研究的目的是评估依洛尤单抗在开放标签扩展试验中的长期疗效、安全性和耐受性。
完成主要试验的患者以 2:1 的比例重新随机分配至依洛尤单抗加标准治疗（SOC）或单独 SOC 治疗 52 周（长期 LDL-C 评估的开放标签研究[OSLER-1]）或 48 周（OSLER-2）。依洛尤单抗的剂量为 QM 420mg（OSLER-1）和 Q2W 140mg 或 QM 420mg（OSLER-2）。对来自 HeFH 患者的这部分患者进行了 OSLER 数据的汇总分析。
来自 RUTHERFORD（n=147）和 RUTHERFORD-2（n=293）的 440 名 HeFH 患者（平均[标准差]年龄 51[12]岁，58%为男性，90%为白人）被随机分配至依洛尤单抗加 SOC（n=289）或 SOC（n=151）。425 名患者（96.6%）完成了 48 周的治疗。8 名患者（2.8%）停止使用依洛尤单抗加 SOC，7 名患者（4.6%）停止使用 SOC。与基线相比，接受依洛尤单抗加 SOC 治疗的患者在 48 周后低密度脂蛋白胆固醇平均降低 53.6%。在 1 年 SOC 对照期间，没有患者发生导致依洛尤单抗永久停药的不良事件。两组的严重不良事件发生率相似（依洛尤单抗加 SOC，7.3%；SOC，8.6%）。
在 HeFH 患者中继续使用依洛尤单抗加 SOC 治疗，可在 48 周的随访期间持续显著降低 LDL-C。SOC 长期使用依洛尤单抗是安全且耐受良好的。
