title: Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.
abstract: BACKGROUND
  Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk.
  
  
  METHODS
  116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat.
  
  
  RESULTS
  At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo.
  
  
  CONCLUSIONS
  These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.
authors.affiliation: Centre for Rheumatic Diseases, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: McCarey
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Rajan
authors.initials: R
authors.lastname: Madhok
authors.forename: Rosie
authors.initials: R
authors.lastname: Hampson
authors.forename: Olga
authors.initials: O
authors.lastname: Scherbakov
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Capell
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000069059:Atorvastatin; D015415:Biomarkers / Q000032:analysis; D001799:Blood Sedimentation; D001809:Blood Viscosity; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D005938:Glucocorticoids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D014841:von Willebrand Factor; D002097:C-Reactive Protein; D000069059:Atorvastatin; D008727:Methotrexate