Key result
Evolocumab sustains ~56% LDL-C reduction over 5 years with adverse event rates comparable to standard care.
Why the study?
Evolocumab and other anti-PCSK9 antibodies reduced cardiovascular outcomes in high-risk patients over less than 3 years, but longer-term effects were unknown.
Does long-term treatment with evolocumab 420 mg monthly safely maintain LDL-C reduction over 5 years in patients with hypercholesterolemia?
RCT (n=1,255)
Open-label
Does long-term treatment with evolocumab 420 mg monthly safely maintain LDL-C reduction over 5 years in patients with hypercholesterolemia?
Evolocumab provides sustained, safe, and well-tolerated LDL-C reduction by approximately 56% over 5 years of treatment in patients with hypercholesterolemia.
Supports long-term evolocumab use in hypercholesterolemia; extends RCT safety data but leaves open real-world outcome benefits.
BACKGROUND: Evolocumab and other anti-PCSK9 antibodies reduced adverse cardiovascular outcomes in clinical trials of high-risk patients over <3 years median treatment duration. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).
No takes yet. Share an insight, caveat, or question.
Koren et al. (2019) conducted an RCT in Hypercholesterolemia (n=1,255). Evolocumab vs. Standard of care was evaluated on Persistence of lipid effects (LDL-C reduction) and exposure-dependent safety. Evolocumab persistently lowered LDL-C by 56% over 5 years with yearly serious adverse event rates of 6.9% to 7.9%, comparable to standard of care, and no neutralizing antibodies detected.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: