title: Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations.
authors: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors: Amirhossein
authors: A
authors: Sahebkar
authors: Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Paolo
authors: P
authors: Di Giosia
authors: Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Cosimo Andrea
authors: CA
authors: Stamerra
authors: Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Davide
authors: D
authors: Grassi
authors: Area di Geriatria, Università Campus Biomedico di Roma, Rome, Italy.
authors: Claudio
authors: C
authors: Pedone
authors: Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche (DISCO), Università Politecnica delle Marche, Ancona, Italy.
authors: Gianna
authors: G
authors: Ferretti
authors: Dipartimento di Scienze della Vita e dell'Ambiente (DISVA), Università Politecnica delle Marche, Ancona, Italy.
authors: Tiziana
authors: T
authors: Bacchetti
authors: Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Claudio
authors: C
authors: Ferri
authors: Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Paolo
authors: P
authors: Giorgini
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D000091362:PCSK9 Inhibitors; D002097:C-Reactive Protein; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab
keywords: PCSK9 inhibitors; atherosclerosis; hs-CRP; inflammation; pleiotropic effect