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Diabetes Metab. 2019 Sep 15:101120. doi: 10.1016/j.diabet.2019.101120. [Epub ahead of print]

Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 Phase 3 ODYSSEY trials.

Author information

1
Hospital Universitario Virgen de la Victoria (IBIMA), Málaga University and CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Malaga, Spain. Electronic address: fjtinahones@uma.es.
2
Department of Cardiology, Leipzig University Hospital, Leipzig, Germany.
3
L'institut du Thorax, Department of Endocrinology, CIC INSERM 1413, CHU Nantes, Nantes, France.
4
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
5
Sanofi, Bridgewater, NJ, USA.
6
Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Abstract

AIMS:

Increased body mass index (BMI) contributes to cardiovascular risk and may influence efficacy of therapeutic antibodies. We investigated the effect of baseline BMI on efficacy and safety of alirocumab, a PCSK9 monoclonal antibody.

METHODS:

In a post-hoc analysis, data were pooled from 10 Phase 3 trials (n=4975) of alirocumab vs. placebo/ezetimibe controls. Alirocumab dose was 150mg every 2 weeks in two trials, and 75mg every 2 weeks with possible increase to 150mg at 12 weeks (based on Week 8 low-density lipoprotein cholesterol [LDL-C]) in eight trials. Efficacy/safety data were assessed in baseline BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2.

RESULTS:

Baseline LDL-C levels were lower among patients in the higher BMI subgroups. Significant LDL-C reductions from baseline were observed at Weeks 12 and 24 for alirocumab vs. controls, of similar magnitude regardless of baseline BMI (interaction P-value=0.7119). LDL-C<1.81mmol/L (<70mg/dL) was achieved at Week 24 by 69.8-76.4% of alirocumab-treated patients and 9.7-18.4% of control-treated patients, with no pattern by BMI. A greater proportion of patients in higher vs. lower BMI subgroups required alirocumab dose increase (P=0.0343); proportions were 22.5%, 24.9%, 31.7%, and 27.2% of patients across BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2, respectively. Adverse event frequencies were similar regardless of BMI; injection-site reaction frequency was higher with alirocumab (5.1-8.2% across BMI categories) vs. controls (3.6-4.8%).

CONCLUSIONS:

Alirocumab provided consistent LDL-C reductions, with similar safety findings across BMI subgroups.

KEYWORDS:

Alirocumab; Body mass index; LDL-C; Obesity; PCSK9 inhibitor

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