Efficacy and Safety of Alirocumab Versus Ezetimibe Over 2 Years (from ODYSSEY COMBO II)

Mahfouz El Shahawy, Christopher P Cannon, Dirk J Blom, James M McKenney, Bertrand Cariou, Guillaume Lecorps, Robert Pordy, Umesh Chaudhari, Helen M Colhoun

Research output: Contribution to journalArticlepeer-review

Abstract

The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to substantially reduce low-density lipoprotein cholesterol (LDL-C). Demonstrating whether efficacy and safety are maintained over a long duration of exposure is vital for clinical decision-making. The COMBO II trial compared the efficacy and safety of alirocumab versus ezetimibe over 2 years. A prespecified first analysis was reported at 52 weeks. Here we report the final end-of-study data (on-treatment) and evaluate post hoc the safety profile with longer versus shorter duration of alirocumab exposure. Patients (n = 720) on maximally tolerated statin dose were treated with alirocumab (75/150 mg every 2 weeks) or ezetimibe (10 mg/day). Overall mean adherence for both treatment groups during the first and second year was >97%. At 2 years, LDL-C was reduced by 49% (alirocumab) versus 17% (ezetimibe; p <0.0001), and LDL-C <70 mg/dl was achieved by 73% of alirocumab-treated versus 40% of ezetimibe-treated patients. Overall safety was similar in both treatment groups at 2 years and during the first versus the second year. Local injection-site reactions were reported by 2.5% (alirocumab) versus 0.8% (ezetimibe) during the first year, and 0.2% versus 0.5% during the second year, indicating early occurrence during prolonged alirocumab exposure. Two consecutive calculated LDL-C values <25 mg/dl were observed in 28% of alirocumab-treated patients (vs 0.4% with ezetimibe). Persistent anti-drug antibody responses were observed in 1.3% (6 of 454) of alirocumab-treated versus 0.4% (1 of 231) of ezetimibe-treated patients. Neutralizing antibodies (that inhibit binding in vitro) were observed in 1.5% (7 of 454) of alirocumab-treated patients (0 with ezetimibe), mostly at isolated time points. Alirocumab sustained substantial LDL-C reductions and was well tolerated up to 2 years in the COMBO II trial.

Original languageEnglish
Pages (from-to)931-939
Number of pages9
JournalAmerican Journal of Cardiology
Volume120
Issue number6
Early online date28 Jun 2017
DOIs
Publication statusPublished - 15 Sep 2017

Keywords

  • Antibodies, Monoclonal
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Clinical Decision-Making
  • Coronary Disease
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Ezetimibe
  • Female
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia
  • Injections, Subcutaneous
  • Male
  • Medication Adherence
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

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