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Safety of Alirocumab (A PCSK9 Monoclonal Antibody) from 14 Randomized Trials
Journal article   Open access   Peer reviewed

Safety of Alirocumab (A PCSK9 Monoclonal Antibody) from 14 Randomized Trials

Peter H Jones, Harold E Bays, Umesh Chaudhari, Robert Pordy, Christelle Lorenzato, Kathryn Miller and Jennifer G Robinson
The American journal of cardiology, Vol.118(12), pp.1805-1811
12/15/2016
DOI: 10.1016/j.amjcard.2016.08.072
PMID: 27729106
url
https://doi.org/10.1016/j.amjcard.2016.08.072View
Published (Version of record) Open Access

Abstract

Previous individual trials of alirocumab (a PCSK9 monoclonal antibody) showed significant low-density lipoprotein cholesterol reductions with overall treatment-emergent adverse event (TEAE) rates comparable with controls. This analysis evaluated safety data from 14 trials (4 phase 2 and 10 phase 3, 8 to 104 weeks; n = 5,234), in 2 pools according to control (placebo/ezetimibe). Overall, 3,340 patients received alirocumab (4,029 patient-years' exposure), 1,276 received placebo, and 618 received ezetimibe. Incidence of deaths, serious TEAEs, discontinuations because of TEAEs, and overall TEAEs were similar between alirocumab and control groups. Alirocumab was associated with a higher incidence of local injection site reactions (7.4% vs 5.3% with placebo; 3.1% vs 2.3% with ezetimibe), pruritus (1.3% vs 0.4% placebo; 0.9% vs 0.5% ezetimibe), and upper respiratory tract infection signs and symptoms (2.1% vs 1.1% placebo; 1.3% vs 0.8% ezetimibe). Incidence of musculoskeletal, neurologic, neurocognitive, ophthalmologic, hepatic events, and TEAEs related to diabetes/diabetes complications was similar between alirocumab and control groups. In a prespecified analysis of phase 3 studies, adjudicated major adverse cardiovascular events (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, and unstable angina requiring hospitalization) occurred in 1.8% alirocumab versus 2.6% placebo patients (hazard ratio 0.69, 95% confidence interval 0.43 to 1.11) and 2.8% alirocumab versus 1.5% ezetimibe patients (hazard ratio 1.4, 95% confidence interval 0.65 to 3.02). In conclusion, pooled safety data from 14 trials demonstrate that alirocumab is generally well tolerated with a favorable safety profile.
 Back Pain - chemically induced Myocardial Infarction - epidemiology Humans Middle Aged Nasopharyngitis - chemically induced Antibodies, Monoclonal - adverse effects Coronary Disease - epidemiology Hypercholesterolemia - drug therapy Diabetes Mellitus, Type 2 - epidemiology Clinical Trials, Phase III as Topic Urinary Tract Infections - chemically induced Respiratory Tract Infections - chemically induced Stroke - epidemiology Pruritus - chemically induced Hypercholesterolemia - epidemiology Acute Coronary Syndrome - epidemiology Comorbidity Ezetimibe - adverse effects Angina, Unstable - epidemiology Influenza, Human - chemically induced Anticholesteremic Agents - adverse effects Randomized Controlled Trials as Topic Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Aged Clinical Trials, Phase II as Topic

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