Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms

Br J Clin Pharmacol. 2016 Jun;81(6):1175-90. doi: 10.1111/bcp.12905. Epub 2016 Apr 3.

Abstract

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low-density lipoprotein cholesterol (LDL-C)-lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high-sensitivity C-reactive protein (hs-CRP) levels through a meta-analysis of randomized controlled trials (RCTs).

Methods: A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs-CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics.

Results: Sixteen treatment arms, with a total of 2546 participants, were included. Random-effects meta-analysis did not show any significant effect of PCSK9 inhibitors on hs-CRP levels (WMD: 0.002 mg l(-1) , CI: -0.017, 0.021; P = 0.807; I(2) = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l(-1) , CI: -0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l(-1) , CI: -0.11, 0.40; P = 0.259; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 0%). Random-effects meta-regression did not suggest any association of changes in hs-CRP levels with changes in plasma LDL-C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980).

Conclusions: This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations.

Keywords: PCSK9 inhibitors; atherosclerosis; hs-CRP; inflammation; pleiotropic effect.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism*
  • Cholesterol, LDL / blood
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Proprotein Convertase 9 / antagonists & inhibitors*
  • Proprotein Convertase 9 / immunology*
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Enzyme Inhibitors
  • C-Reactive Protein
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • evolocumab
  • alirocumab