Article Text

Extended report
Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study
  1. Iain B McInnes1,
  2. Liz Thompson2,
  3. Jon T Giles3,
  4. Joan M Bathon3,
  5. Jane E Salmon4,
  6. Andre D Beaulieu5,
  7. Christine E Codding6,
  8. Timothy H Carlson7,
  9. Christian Delles1,
  10. Janet S Lee8,
  11. Naveed Sattar1
  1. 1University of Glasgow, Glasgow, UK
  2. 2Roche Products Ltd, Welwyn Garden City, UK
  3. 3Columbia University, New York, New York, USA
  4. 4Hospital for Special Surgery—Weill Cornell Medical College, New York, New York, USA
  5. 5Centre Hospitalier de l'Université Laval, Quebec City, Quebec, Canada
  6. 6Health Research of Oklahoma, Oklahoma City, Oklahoma, USA
  7. 7Pacific Biomarkers, Seattle, Washington, USA
  8. 8Roche, Nutley, New Jersey, USA
  1. Correspondence to Professor Iain B McInnes, Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK; Iain.McInnes{at}glasgow.ac.uk

Abstract

Objectives 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.

  • Cardiovascular Disease
  • Lipids
  • Inflammation
  • Rheumatoid Arthritis
  • DMARDs (biologic)

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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