title: Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To conduct a robust, double-blind, placebo-controlled study examining the effects of tumor necrosis factor (TNF) modulation on concentrations of traditional and novel cardiovascular disease risk factors in patients with an inflammatory condition.
  
  
  METHODS
  In this double-blind study, 127 patients with psoriatic arthritis (PsA) and active psoriasis were randomized to 1 of 3 treatment arms (placebo, onercept 50 mg, or onercept 100 mg for 12 weeks). Traditional and novel biochemical risk factors were evaluated at baseline and at the end of the treatment period.
  
  
  RESULTS
  At baseline, an elevated C-reactive protein (CRP) level correlated positively with lipoprotein(a) (Lp[a]), intercellular adhesion molecule 1, interleukin-6, and homocysteine levels but was inversely correlated with concentrations of all other lipid moieties and sex hormone binding globulin (SHBG). Onercept at a dose of 100 mg induced significant (P < or = 0.002) reductions in the levels of CRP (-14.0 versus 6.5 mg/liter with placebo), Lp(a) (-3.11 versus 1.52 mg/dl with placebo), and homocysteine (-1.72 versus 0.34 mumoles/liter with placebo) and an increase in the SHBG concentration (4.3 versus -1.3 mmoles/liter with placebo). The 100-mg dose of onercept was also associated with significant (P < 0.05) increases in the level of circulating apolipoprotein AI (Apo A-I) (4.0 versus -5.6 mg/dl with placebo); however, levels of Apo B (6.3 versus -0.4 mg/dl with placebo) and triglycerides (0.09 versus 0.04 mmoles/liter) were also increased.
  
  
  CONCLUSIONS
  This study is the first to demonstrate that targeting the TNF pathway can significantly decrease Lp(a) and homocysteine levels and elevate Apo A-I and SHBG concentrations. These data support an important precursor role for high-grade inflammation in modulating these putative risk parameters. However, TNF blockade-induced increases in triglyceride and Apo B levels were unexpected and suggest that it is not possible, on the basis of biochemical changes in isolation, to suggest that cardioprotection would necessarily follow; rather, direct measures of atherosclerotic progression with TNF blockade (e.g., using carotid ultrasound) would be better.
authors.affiliation: University of Glasgow, Glasgow, UK. nsattar@clinmed.gla.ac.uk
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Philippa
authors.initials: P
authors.lastname: Crompton
authors.forename: Lynne
authors.initials: L
authors.lastname: Cherry
authors.forename: David
authors.initials: D
authors.lastname: Kane
authors.forename: Gordon
authors.initials: G
authors.lastname: Lowe
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D015535:Arthritis, Psoriatic / Q000097:blood / Q000150:complications*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000627:therapeutic use*; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D053319:Tumor Necrosis Factor Decoy Receptors / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D016632:Apolipoprotein A-I; D017270:Lipoprotein(a); D047888:Receptors, Tumor Necrosis Factor, Type I; D012738:Sex Hormone-Binding Globulin; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; C069521:recombinant human tumor necrosis factor-binding protein-1; D002784:Cholesterol