title: Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.
abstract: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression.
  
  
  
  The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging.
  
  
  
  Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta.
  
  
  
  There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test.
  
  
  
  There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930).
authors.affiliation: Oxford Acute Vascular Imaging Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: robin.choudhury@cardiov.ox.ac.uk.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Choudhury
authors.affiliation: Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Oxford, United Kingdom.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Birks
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Mani
authors.affiliation: Oxford Acute Vascular Imaging Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Biasiolli
authors.affiliation: Oxford Acute Vascular Imaging Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Robson
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Philippe L
authors.initials: PL
authors.lastname: L'Allier
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Marc-Alexandre
authors.initials: MA
authors.lastname: Gingras
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Nadia
authors.initials: N
authors.lastname: Alie
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: McLaughlin
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Basson
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Schecter
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Svensson
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Denise
authors.initials: D
authors.lastname: Yates
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: zahi.fayad@mssm.edu.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001158:Arteries / Q000187:drug effects*; D050197:Atherosclerosis / Q000150:complications* / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000150:complications*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; C541220:canakinumab
keywords: C-reactive protein; homeostasis model assessment; inflammation; interleukin-1