title: Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study.
abstract: OBJECTIVE
  The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA.
  
  
  METHODS
  Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo.
  
  
  RESULTS
  Median total-cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels increased in TCZ versus placebo recipients by week 12 (12.6% vs 1.7%, 28.1% vs 2.2%, 10.6% vs -1.9%, respectively; all p<0.01). There were no significant differences in mean small LDL, mean oxidised LDL or total HDL-C concentrations. However, HDL-associated serum amyloid A content decreased in TCZ recipients. TCZ also induced reductions (>30%) in secretory phospholipase A2-IIA, lipoprotein(a), fibrinogen and D-dimers and elevation of paraoxonase (all p<0.0001 vs placebo). The ApoB/ApoA1 ratio remained stable over time in both groups. PWV decreases were greater with placebo than TCZ at 12 weeks (adjusted mean difference 0.79 m/s (95% CI 0.22 to 1.35; p=0.0067)).
  
  
  CONCLUSIONS
  These data provide the first detailed evidence for the modulation of lipoprotein particles and other surrogates of vascular risk with IL-6R inhibition. When compared with placebo, TCZ induced elevations in LDL-C but altered HDL particles towards an anti-inflammatory composition and favourably modified most, but not all, measured vascular risk surrogates. The net effect of such changes for cardiovascular risk requires determination.
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Liz
authors.initials: L
authors.lastname: Thompson
authors.affiliation: Columbia University, New York, New York, USA.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.affiliation: Columbia University, New York, New York, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Bathon
authors.affiliation: Hospital for Special Surgery-Weill Cornell Medical College, New York, New York, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
authors.affiliation: Centre Hospitalier de l'Université Laval, Quebec City, Quebec, Canada.
authors.forename: Andre D
authors.initials: AD
authors.lastname: Beaulieu
authors.affiliation: Health Research of Oklahoma, Oklahoma City, Oklahoma, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Codding
authors.affiliation: Pacific Biomarkers, Seattle, Washington, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Carlson
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.affiliation: Roche, Nutley, New Jersey, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000378:metabolism; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005338:Fibrin Fibrinogen Degradation Products; C508603:IL6R protein, human; D017270:Lipoprotein(a); D019947:Receptors, Interleukin-6; D000685:Serum Amyloid A Protein; D014280:Triglycerides; C036309:fibrin fragment D; D005340:Fibrinogen; D054501:Group II Phospholipases A2; D043303:Aryldialkylphosphatase; C502936:tocilizumab
keywords: Cardiovascular Disease; DMARDs (biologic); Inflammation; Lipids; Rheumatoid Arthritis