title: Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL-6) as a major player in inflammation cascade. IL-6 blockade may reduce cardiovascular risk, but current treatments to block IL-6 also induce dyslipidemia, a finding with an uncertain prognosis.
  
  
  RESULTS
  We aimed to determine the endothelial function responses to the IL-6-blocking agent tocilizumab, anti-tumor necrosis factor α, and synthetic disease-modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16-week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti-tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease-modifying antirheumatic drugs. Forty patients completed the 16-week follow-up period. The main outcome was flow-mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow-mediated dilation percentage variation increased statistically significantly from a pre-treatment mean of (3.43% [95% CI, 1.28-5.58] to 5.96% [95% CI, 3.95-7.97];P=0.03). Corresponding changes were 4.78% (95% CI, 2.13-7.42) to 6.75% (95% CI, 4.10-9.39) (P=0.09) and 2.87% (95% CI, -2.17 to 7.91) to 4.84% (95% CI, 2.61-7.07) (P=0.21) in the anti-tumor necrosis factor α and the synthetic disease-modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59-217.36) to 232.3 (201.62-263.09) (P=0.003) and in the synthetic disease-modifying antirheumatic drug group from 185.8 (95% CI, 169.76-201.81) to 202.8 (95% CI, 176.81-228.76) (P=0.04), but not in the anti-tumor necrosis factor α group. High-density lipoprotein did not change significantly in any group.
  
  
  CONCLUSIONS
  Endothelial function is improved by tocilizumab in a high-risk population, even as it increases total cholesterol and low-density lipoprotein levels.
authors.affiliation: Department of Internal Medicine, Rio de Janeiro State University, Rio de Janeiro, Brazil brunobacchiega@gmail.com.
authors.forename: Bruno Cesar
authors.initials: BC
authors.lastname: Bacchiega
authors.affiliation: Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Bacchiega
authors.affiliation: Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Magali Justina Gomez
authors.initials: MJ
authors.lastname: Usnayo
authors.affiliation: Department of Internal Medicine, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bedirian
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Gurkirpal
authors.initials: G
authors.lastname: Singh
authors.affiliation: Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Geraldo da Rocha Castelar
authors.initials: GD
authors.lastname: Pinheiro
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001938:Brazil / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011159:Population Surveillance; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C502936:tocilizumab
keywords: dyslipidemia; endothelial function; inflammation; tocilizumab