Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study
- Iain B McInnes1,
- Liz Thompson2,
- Jon T Giles3,
- Joan M Bathon3,
- Jane E Salmon4,
- Andre D Beaulieu5,
- Christine E Codding6,
- Timothy H Carlson7,
- Christian Delles1,
- Janet S Lee8,
- Naveed Sattar1
- 1University of Glasgow, Glasgow, UK
- 2Roche Products Ltd, Welwyn Garden City, UK
- 3Columbia University, New York, New York, USA
- 4Hospital for Special Surgery—Weill Cornell Medical College, New York, New York, USA
- 5Centre Hospitalier de l'Université Laval, Quebec City, Quebec, Canada
- 6Health Research of Oklahoma, Oklahoma City, Oklahoma, USA
- 7Pacific Biomarkers, Seattle, Washington, USA
- 8Roche, Nutley, New Jersey, USA
- Correspondence to Professor Iain B McInnes, Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK;
- Received 24 July 2013
- Revised 17 October 2013
- Accepted 2 December 2013
- Published Online First 24 December 2013
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.
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