The Peroxisome Proliferator Activated Receptor-gamma pioglitazone Decreases Cardiovascular Risk and Disease Activity In Patients With Rheumatoid arthritis

Wendy Marder¹, Shokoufeh Khalatbari², James D. Myles³, Rita Hench⁴, Susan Lustig⁴, Srilakshmi Yalavarthi⁵, Aishwarya Parameswaran⁴, Robert Brook² and Mariana J. Kaplan⁶, ¹Division of Rheumatology, University of Michigan, Ann Arbor, MI, ²Medicine, University of Michigan at Ann Arbor, Ann Arbor, MI, ³Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, ⁴University of Michigan, Ann Arbor, MI, ⁵University of Michigan Rheumatology, Ann Arbor, MI, ⁶Systemic Autoimmunity Branch, National Institutes of Health/NIAMS, Bethesda, MD

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease, inflammation and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy II

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor-γ (PPAR-γ) pioglitazone could promote potent vasculoprotective and anti-inflammatory effects in RA, thereby decreasing CV risk and RA disease activity.

Methods:

143 non-diabetic adult RA patients (76.2% female, age 55.2 ± 12.1 (mean +SD) on stable RA standard of care treatment were enrolled in a randomized, double- blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3 month duration/arm with a 2 month-washout period. Brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), pulse wave velocity of the aorta (PWV), microvascular endothelial function (reactive hyperemia index [RHI]) and circulating biomarkers of inflammation, insulin resistance and atherosclerosis risk were quantified. RA disease activity was assessed with the 28 Joint-Disease Activity Scale-C-reactive protein (DAS28-CRP) and the SF-36 quality of life questionnaire.

Results:

When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (i.e., aortic stiffness) (p=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (p=0.02) and CRP levels (p=0.001), while improving lipid profiles. The drug was well tolerated.

Conclusion:

Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues.

Disclosure:

W. Marder,
None;

S. Khalatbari,
None;

J. D. Myles,
None;

R. Hench,
None;

S. Lustig,
None;

S. Yalavarthi,
None;

A. Parameswaran,
None;

R. Brook,
None;

M. J. Kaplan,

Takeda Pharmaceuticals, U.S.A., Inc.,

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