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

McInnes, I. B. et al. (2015) Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Annals of the Rheumatic Diseases, 74(4), pp. 694-702. (doi: 10.1136/annrheumdis-2013-204345) (PMID:24368514) (PMCID:PMC4392313)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Delles, Professor Christian and Sattar, Professor Naveed
• Authors: McInnes, I. B., Thompson, L., Giles, J. T., Bathon, J. M., Salmon, J. E., Beaulieu, A. D., Codding, C. E., Carlson, T. H., Delles, C., Lee, J. S., and Sattar, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Annals of the Rheumatic Diseases
• Publisher: B M J Group
• ISSN: 0003-4967
• ISSN (Online): 1468-2060
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in Annals of the Rheumatic Diseases 74(4):694-702
• Publisher Policy: Reproduced under a Creative Commons License