阿利西尤单抗和依洛尤单抗在最大耐受胆固醇降低治疗基础上的疗效、安全性、低密度脂蛋白胆固醇降低作用及计算得出的10年心血管风险降低情况：一项上市后研究
Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study.
作者信息
Shah Parth, Glueck Charles J, Goldenberg Naila, Min Sarah, Mahida Chris, Schlam Ilana, Rothschild Matan, Huda Ali, Wang Ping
机构信息
Graduate Medical Education Department, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
The Jewish Hospital Internal Medicine Residency Program, 4777 E Galbraith Rd, Cincinnati, Ohio, 45236, USA.
出版信息
Lipids Health Dis. 2017 Jan 23;16(1):19. doi: 10.1186/s12944-017-0416-7.
BACKGROUND
Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO.
METHODS
Post-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO.
RESULTS
Of 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins. At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (-54%), on ALI 150 mg from 175 to 57 mg/dL (-63%), and on EVO 140 mg from 165 to 69 mg/dL (-63%), p <0.0001 for all. Absolute and percent LDLC reduction did not differ (p >.05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05). Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg -22 and -44%, ALI 150 mg -31 and -50%, and EVO 140 mg -29 and -56%, p ≤.002 for all. The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%.
CONCLUSION
In patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.
背景
此前已通过针对特定患者群体的对照临床试验对前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂阿利西尤单抗（ALI）和依洛尤单抗（EVO）的疗效和安全性进行了评估。在上市后，对于杂合子家族性高胆固醇血症（HeFH）患者和/或患有心血管疾病（CVD）且在最大耐受的降胆固醇治疗下低密度脂蛋白胆固醇（LDLC）降低未达最佳水平的患者，我们评估了ALI和EVO的疗效和安全性。
方法
在上市后，我们让25名患者开始使用75毫克的ALI，15名患者使用150毫克的ALI，32名患者每两周使用140毫克的EVO，并将其添加到初始LDLC降低方案中，随访时间中位数为24周。收集病史、体格检查、人口统计学和不良事件数据。评估了ALI和EVO治疗后LDLC以及美国心脏协会（AHA）和美国国立卫生研究院（NIH）计算的10年心血管疾病风险的变化。
结果
72名患者中，25名仅患有HeFH，25名仅患有CVD，22名两者都有，中位年龄为65岁，女性占63%，男性占38%，86%为白种人，11%为非裔美国人，17%为糖尿病患者，63%正在服用抗高血压药物，7%为吸烟者。入组时，30名（42%）正在服用他汀类药物，42名（58%）无法耐受任何他汀类药物。在24周时，75毫克ALI组的LDLC中位数从117降至62毫克/分升（-54%），150毫克ALI组从175降至57毫克/分升（-63%），140毫克EVO组从165降至69毫克/分升（-63%），所有组p均<0.0001。150毫克ALI组和140毫克EVO组之间LDLC的绝对降低值和降低百分比无差异（p>0.05），但75毫克ALI组低于150毫克ALI组和140毫克EVO组（p<0.05）。AHA和NIH计算器计算的10年心血管疾病风险降低百分比分别为：75毫克ALI组为-22%和-44%，150毫克ALI组为-31%和-50%，140毫克EVO组为-29%和-56%，所有组p≤0.002。三种最常见的不良事件包括类流感性肌炎10%、呼吸道症状8%和注射部位反应6%。
结论
在HeFH和/或CVD患者中，140毫克EVO组和150毫克ALI组的LDLC降低了63%，75毫克ALI组降低了54%。不良事件极少且可耐受。ALI和EVO代表了LDLC降低方面的范式转变。长期来看，上市后的安全性和疗效仍有待确定。
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