Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study.

Autor:	McInnes IB; University of Glasgow, Glasgow, UK., Thompson L; Roche Products Ltd, Welwyn Garden City, UK., Giles JT; Columbia University, New York, New York, USA., Bathon JM; Columbia University, New York, New York, USA., Salmon JE; Hospital for Special Surgery-Weill Cornell Medical College, New York, New York, USA., Beaulieu AD; Centre Hospitalier de l'Université Laval, Quebec City, Quebec, Canada., Codding CE; Health Research of Oklahoma, Oklahoma City, Oklahoma, USA., Carlson TH; Pacific Biomarkers, Seattle, Washington, USA., Delles C; University of Glasgow, Glasgow, UK., Lee JS; Roche, Nutley, New Jersey, USA., Sattar N; University of Glasgow, Glasgow, UK.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2015 Apr; Vol. 74 (4), pp. 694-702. Date of Electronic Publication: 2013 Dec 24.
DOI:	10.1136/annrheumdis-2013-204345
Abstrakt:	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. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
Databáze:	MEDLINE
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