title: Safety of Alirocumab (A PCSK9 Monoclonal Antibody) from 14 Randomized Trials.
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.
authors.affiliation: Baylor College of Medicine, Houston, Texas. Electronic address: jones@bcm.edu.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Jones
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (L-MARC), Louisville, Kentucky.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.affiliation: Sanofi, Bridgewater, New Jersey.
authors.forename: Umesh
authors.initials: U
authors.lastname: Chaudhari
authors.affiliation: Regeneron, Tarrytown, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Pordy
authors.affiliation: Sanofi, Chilly-Mazarin, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lorenzato
authors.affiliation: Regeneron, Basking Ridge, New Jersey.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Miller
authors.affiliation: University of Iowa, Iowa City, Iowa.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
mesh_terms: D054058:Acute Coronary Syndrome / Q000453:epidemiology; D000368:Aged; D000789:Angina, Unstable / Q000453:epidemiology; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects*; D001416:Back Pain / Q000139:chemically induced; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D003327:Coronary Disease / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D000069438:Ezetimibe / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology; D007251:Influenza, Human / Q000139:chemically induced*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009304:Nasopharyngitis / Q000139:chemically induced*; D011537:Pruritus / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000139:chemically induced*; D020521:Stroke / Q000453:epidemiology; D014552:Urinary Tract Infections / Q000139:chemically induced*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe; C571059:alirocumab