Author + information
- Received August 2, 2016
- Revision received November 2, 2016
- Accepted November 2, 2016
- Published online January 30, 2017.
- Jennifer G. Robinson, MD, MPHa,∗ (, )
- Robert S. Rosenson, MDb,
- Michel Farnier, MD, PhDc,
- Umesh Chaudhari, MDd,
- William J. Sasiela, PhDe,
- Laurence Merlet, MSf,
- Kathryn Miller, MSg and
- John J.P. Kastelein, MD, PhDh
- aUniversity of Iowa, Iowa City, Iowa
- bIcahn School of Medicine at Mount Sinai, New York, New York
- cPoint Médical, Dijon, France
- dSanofi, Bridgewater, New Jersey
- eRegeneron Pharmaceuticals, Inc., Tarrytown, New York
- fSanofi, Chilly-Mazarin, France
- gRegeneron Pharmaceuticals, Inc., Basking Ridge, New Jersey
- hDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
- ↵∗Address for correspondence:
Dr. Jennifer G. Robinson, Departments of Epidemiology & Medicine, College of Public Health, University of Iowa, 145 N. Riverside Drive, S455 CPBH, Iowa City, Iowa 52242.
Background Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy.
Objectives The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values <25 or <15 mg/dl in the ODYSSEY program, with follow-up as long as 104 weeks.
Methods Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years’ exposure).
Results In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values <25 mg/dl, and 314 (9.4%) achieved <15 mg/dl. Baseline LDL-C was lower (mean 100.3 vs. 134.3 mg/dl) in patients with LDL-C <25 versus ≥25 mg/dl. Similar rates of adverse events occurred in patients achieving LDL-C <25 and <15 mg/dl (72.7% and 71.7%, respectively), compared with 76.6% in those who did not achieve LDL-C <25 mg/dl. Neurological and neurocognitive events were similar among the 3 groups. In a propensity score analysis, the rate of cataracts was higher in patients with LDL-C <25 mg/dl (2.6%) versus ≥25 mg/dl (0.8%; hazard ratio: 3.40; 95% confidence interval: 1.58 to 7.35). However, no difference in cataract incidence was observed between pooled alirocumab and control groups.
Conclusions LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events, although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl. (Pooled analyses of already reported trials; NCT01288443, NCT01288469, NCT01266876, NCT01812707, NCT01507831, NCT01617655, NCT01623115, NCT01709500, NCT01644175, NCT01644188, NCT01730040, NCT01730053, NCT01644474, and NCT01709513)
This analysis was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing support was provided by Rob Campbell of Prime Medica Ltd., Knutsford, Cheshire, United Kingdom, supported by Sanofi and Regeneron Pharmaceuticals, Inc. Dr. Robinson has received research funding from Amarin, Amgen, AstraZeneca, Eli Lilly, Esai, GlaxoSmithKline, Merck, Pfizer, Regeneron Pharmaceuticals, Inc./Sanofi, and Takeda; and acted as a consultant and/or advisory panel member for Akcea/Ionis, Amgen, Eli Lilly, Esperion, Merck, Pfizer, and Regeneron/Sanofi. Dr. Rosenson has received research funding from Akcea, Amgen, AstraZeneca, Catabasis, The Medicines Company, Regeneron Pharmaceuticals, Inc., and Sanofi; and acted as a consultant and/or advisory board panel member for Akcea, Amgen, AstraZeneca, Eli Lilly, Regeneron Pharmaceuticals, Inc., and Sanofi. Dr. Farnier has received research support from and participated in a speakers bureau for Amgen, Merck, and Sanofi; has received honoraria from Abbott, Eli Lilly, and Pfizer; and acted as a consultant and/or advisory panel member for Amgen, Akcea/Ionis, AstraZeneca, Roche, Kowa, Merck, Mylan, Pfizer, Sanofi/Regeneron Pharmaceuticals, Inc., and Servier. Drs. Chaudhari and Merlet are stockholders and employees of Sanofi. Drs. Sasiela and Miller are stockholders and employees of Regeneron Pharmaceuticals, Inc. Dr. Kastelein has received consulting fees from Cerenis, The Medicines Company, CSL Behring, Amgen, Regeneron Pharmaceuticals, Inc., Eli Lilly, Esperion, AstraZeneca, Catabasis, UniQure, Novartis, Merck, Ionis Pharmaceuticals, Kowa, and Pfizer. P. K. Shah, MD, served as Guest Editor-in-Chief for this paper. Robert Giugliano, MD, SM, served as Guest Associate Editor for this paper.
- Received August 2, 2016.
- Revision received November 2, 2016.
- Accepted November 2, 2016.
- The Authors