title: Effect of alirocumab dose increase on LDL lowering and lipid goal attainment in patients with dyslipidemia.
abstract: The objective of this study is to report the dose response in ODYSSEY phase 3 clinical trials of proprotein convertase subtilisin kexin type 9 inhibition with alirocumab in patients not at prespecified lipid goals who received a per-protocol dose increase from 75 every 2 weeks (Q2W) to 150 mg Q2W.
  
  
  
  Patients (n=2181) receiving statins were enrolled in six phase 3 randomized, double-blind, double-dummy trials (24-104 weeks): alirocumab versus placebo or ezetimibe 10 mg/day. The 75 mg subcutaneous Q2W dose was increased to 150 mg at week 12 if week 8 LDL cholesterol (LDL-C) was greater than or equal to 70 mg/dl (>100 mg/dl in OPTIONS studies for patients without previous coronary heart disease, but with other risk factors). LDL-C percentage reductions from baseline (on-treatment data, n=1291) were compared at week 12 versus week 24.
  
  
  
  Most patients (n=951; 73.7%) with 75 mg Q2W dose plus background statin achieved LDL-C less than 70 or less than 100 mg/dl at week 8. In 340 (26.3%) patients, alirocumab dose was increased to 150 mg Q2W at week 12, and 60.9% of these patients achieved LDL-C goals at week 24, with an additional 14.2% reduction in LDL-C from week 12 to week 24. Adverse event rates were comparable in patients with versus without a dose increase (72.4 vs. 71.8% in placebo-controlled trials; 67.0 vs. 67.6% in ezetimibe-controlled trials).
  
  
  
  Most patients achieved LDL-C goals with alirocumab 75 mg Q2W plus statins. Of those (26.3%) receiving a dose increase, 60.9% achieved LDL-C goals at week 24 with an additional 14.2% reduction in LDL-C.
authors.affiliation: aDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands bThe Christ Hospital, Heart and Vascular Center/The Lindner Research Center, Cincinnati, Ohio cHarvard Clinical Research Institute, Boston, Massachusetts dLouisville Metabolic and Atherosclerosis Research Center (L-MARC), Louisville, Kentucky eSanofi, Bridgewater, New Jersey fRegeneron Pharmaceuticals Inc., Tarrytown, New York, USA gBiostatistics and Programming, Sanofi, Chilly-Mazarin hPoint Médical, Dijon, France.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.forename: Pascal
authors.initials: P
authors.lastname: Minini
authors.forename: L Veronica
authors.initials: LV
authors.lastname: Lee
authors.forename: Jaman
authors.initials: J
authors.lastname: Maroni
authors.forename: Michel
authors.initials: M
authors.lastname: Farnier
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; C571059:alirocumab