Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Lipid and Inflammation Parameters: A Translational, Randomized Placebo-Controlled Study To Evaluate Effects of Tocilizumab: The MEASURE Study.

McInnes7,  Iain B., Lee6,  Janet S., Wu6,  Wen, Giles5,  Jon T., Bathon5,  Joan M., Salmon4,  Jane E., Beaulieu2,  Andre D.

British Heart Foundation, Glasgow, United Kingdom
Centre de Rhumatologie St-Louis, Montreal, QC, Canada
Health Research of Oklahoma, Oklahoma City, OK
Hospital for Special Surgery, New York, NY
Johns Hopkins University, Baltimore, MD
Roche, Nutley, NJ
University of Glasgow, United Kingdom

Purpose:

Mechanistic data describing changes in lipid parameters upon IL-6R inhibition with tocilizumab (TCZ) are lacking. We report initial results from a randomized, double-blind, placebo-controlled study to evaluate the impact of TCZ on lipid particle subclasses and markers potentially relevant to cardiovascular (CV) risk.

Methods:

Serum lipid subclasses characterized by nuclear magnetic resonance (NMR) and a range of inflammatory biomarkers were measured in patients with active rheumatoid (RA) with an inadequate response to MTX. Changes from baseline (BL) to wk 12 were compared between TCZ 8 mg/kg + MTX (N=69) and PBO+MTX (N=63) arms. The data were analyzed using nonparametric analysis of variance, not corrected for multiplicity.

Results:

Baseline values and changes from baseline for each parameter by treatment arm are shown in the Table. Within lipid parameters, the largest changes occurred in the VLDL/triglyceride and large VLDL. Within LDL, increases occurred almost exclusively in large, more buoyant particles whereas small, dense LDL particles remained stable. Within HDL, increases occurred primarily in small HDL particles. Among inflammatory markers, Hs-CRP, HDL-associated SAA, and sPLA2-IIA were reduced with TCZ treatment; the prothrombotic marker D-dimer was also reduced. The HDL-associated antioxidative enzyme, paraoxonase I was increased with TCZ treatment.

Conclusion:

Small LDL particles, thought to be proatherogenic, did not increase with TCZ treatment, in contrast to large VLDL particles and in small HDL particles with statistically significant increases. The changes in lipid parameters that occur with TCZ treatment, coupled with reductions in a wide range of inflammatory markers, demonstrate the intrinsic linkage of inflammation and metabolic regulation in the context of RA. Furthermore, reductions in HDL-associated SAA and sPLA2-IIA along with increases in paraoxonase reflect qualitative changes in lipoproteins that may favor improvements in CV risk-benefit.

 TCZ 8MG/KG + MTX N = 69PBO + MTX N = 63 
 Median BL (n)Median Cfb to Wk 12 (n)Median BL (n)Median Cfb to Wk 12 (n)P Value
VLDL Triglycerides (mg/dL)56.0 (63)39.0 (55)63.0 (59)2.5 (56)<0.0001
Large VLDL/Chylomicrons (nmol/L)1.3 (63)1.1 (55)1.1 (59)0.0 (56)0.0026
Small LDL Particle (nmol/L)693 (63)-14 (55)843 (59)29.5 (56)>0.1
Small HDL (mmol/L)17.4 (63)3.9 (55)19.9 (59)0.6 (56)0.0001
Hs-CRP (mg/dL)0.9 (69)-0.8 (60)0.9 (63)0.1 (61)<0.0001
HDL SAA (mg/L)9.3 (60)-6.0 (53)6.7 (57)0.6 (54)<0.0001
Paraoxonase (U/L)27.4 (64)3.3 (56)14.3 (58)0.0 (55)<0.0001
D-Dimer (ng/mL)1032 (68)-639 (62)806 (63)-60.0 (60)<0.0001
sPLA2-IIA (ng/mL)6.7 (66)-4.3 (58)6.9 (62)0.1 (59)<0.0001
BL = Baseline; Cfb = change from baseline

To cite this abstract, please use the following information:
McInnes, Iain B., Lee, Janet S., Wu, Wen, Giles, Jon T., Bathon, Joan M., Salmon, Jane E., et al; Lipid and Inflammation Parameters: A Translational, Randomized Placebo-Controlled Study To Evaluate Effects of Tocilizumab: The MEASURE Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1441
DOI: 10.1002/art.29207

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