Jacksonville Center for Clinical Research, Jacksonville, Florida.
Thrombolysis In Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
J Am Coll Cardiol. 2019 Oct 29;74(17):2132-2146. doi: 10.1016/j.jacc.2019.08.1024.
Evolocumab and other anti-PCSK9 antibodies reduced adverse cardiovascular outcomes in clinical trials of high-risk patients over <3 years median treatment duration.
The OSLER-1 trial (Open Label Study of Long Term Evaluation Against LDL-C Trial) evaluated longer-term effects of evolocumab during open-label hypercholesterolemia treatment for up to 5 years.
Patients randomized to standard of care (SOC) or evolocumab 420 mg monthly (evolocumab + SOC) for year 1. After year 1, patients could enter the all-evolocumab period and receive evolocumab + SOC for an additional 4 years. The authors analyzed the persistence of lipid effects and exposure-dependent safety focusing on yearly rates of adverse events (AEs) and anti-drug antibodies over 4.951 patient-years of observation.
A total of 1,255 patients (safety analysis population) randomized into the year 1 SOC-controlled period and received ≥1 evolocumab dose (mean ± SD age 57 ± 12 years; 53% female). A total of 1,151 patients (efficacy analysis population) progressed to the all-evolocumab period (year 2 and beyond). Evolocumab + SOC persistently lowered mean ± SE low-density lipoprotein cholesterol (LDL-C) by 56% ± 0.6% (n = 1,071), 57% ± 0.8% (n = 1,001), 56% ± 0.8% (n = 943), and 56% ± 0.8% (n = 803) after approximately 2, 3, 4, and 5 years, respectively, from randomization. Mean baseline LDL-C decreased from 140 to 61 mg/dl on treatment. Yearly serious AE rates during evolocumab + SOC ranged from 6.9% to 7.9%, comparable to the 6.8% rate in SOC patients during year 1. Evolocumab discontinuation due to AEs occurred in 5.7% of patients. Two SOC and 2 evolocumab + SOC patients developed new, transient, binding anti-drug antibodies; no neutralizing antibodies were observed.
The OSLER-1 trial demonstrated consistently excellent LDL-C-lowering efficacy, tolerance, and safety of evolocumab, with no neutralizing antibodies detected, throughout the longest-duration study of a PCSK9 inhibitor reported to date. (Open Label Study of Long Term Evaluation Against LDL-C Trial [OSLER-1]; NCT01439880).
依洛尤单抗和其他抗 PCSK9 抗体在高危患者的临床试验中降低了心血管不良结局，中位治疗时间<3 年。
OSLER-1 试验（Open Label Study of Long Term Evaluation Against LDL-C Trial）评估了依洛尤单抗在长达 5 年的开放性高胆固醇血症治疗中的长期效果。
患者随机分为标准治疗（SOC）或依洛尤单抗 420mg 每月（依洛尤单抗+SOC）治疗 1 年。1 年后，患者可以进入全依洛尤单抗治疗期，并额外接受依洛尤单抗+SOC 治疗 4 年。作者分析了脂质作用的持久性和暴露依赖性安全性，重点关注了 4.951 患者年观察期间每年不良事件（AE）和抗药物抗体的发生率。
共有 1255 名患者（安全性分析人群）随机进入第 1 年的 SOC 对照期，并接受了≥1 剂依洛尤单抗（平均年龄为 57 ± 12 岁；53%为女性）。共有 1151 名患者（疗效分析人群）进入全依洛尤单抗治疗期（第 2 年及以后）。依洛尤单抗+SOC 持续降低平均±SE 低密度脂蛋白胆固醇（LDL-C）56%±0.6%（n=1071）、57%±0.8%（n=1001）、56%±0.8%（n=943）和 56%±0.8%（n=803），分别在随机分组后大约 2、3、4 和 5 年。治疗前平均基线 LDL-C 从 140 降至 61mg/dl。依洛尤单抗+SOC 每年严重 AE 发生率为 6.9%至 7.9%，与第 1 年 SOC 患者的 6.8%相似。因 AE 导致的依洛尤单抗停药发生率为 5.7%。2 名 SOC 患者和 2 名依洛尤单抗+SOC 患者出现新的、短暂的、结合性抗药物抗体；未观察到中和抗体。
OSLER-1 试验表明，依洛尤单抗在最长时间的 PCSK9 抑制剂研究中，持续具有优异的 LDL-C 降低效果、耐受性和安全性，未检测到中和抗体。（Open Label Study of Long Term Evaluation Against LDL-C Trial [OSLER-1]；NCT01439880）。
