Abstract 1674: Chronic Inhibition Of Interleukin-1 Activity By Anakinra Is More Effective Than Corticosteroids In Improving Endothelial Function And Coronary Flow Reserve
Background: Interleukin-1 mediates atherogenesis and coronary vasoreactivity. Anakinra, a human recombinant inerleukin-1a receptor antagonist, is used for the treatment of rheumatoid arthritis. We investigated the effects of anakinra on coronary flow, endothelial and arterial function as well as on oxidative stress and endothelin.
Methods: 42 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150mg s.c.) (n= 23) or 5mg prednisolone (n = 19) for 30 days. Twenty-three healthy subjects served as controls. At baseline and 30 days after treatment we assessed a) the coronary flow reserve (CFR) of the LAD, aortic distensibility (AD) using echocardiography b) flow mediated endothelial-dependent dilation of the brachial artery (FMD) c) carotid to femoral artery pulse wave velocity (PWV) and d) C-reactive protein, interleukin 6 (IL-6), malondialdehyde (MDA), nitrotyrosine (NT) and endothelin-1 (ET-1) blood levels. Patients had no ischaemia at treadmill exercise test.
Results: Patients had impaired FMD, CFR, AD, IL6 ,CRP, MDA, NT and ET-1 compared to healthy controls (p < 0.05). Compared to baseline, there was an improvement in FMD (4.8 ± 2.7%, vs. 10.5 ± 4.1%, p < 0.01), CFR (2.4 ± 0.6 vs. 3.08 ± 0.5, p < 0.01), AD (1.56 ± 1.5 vs.. 4.6 ± 3.2 cm2.dyn-1.10 – 6, p < 0.01), MDA (2.8 ± 2 v.1.5 ± 0.7 μM, p < 0.05), NT (median 787 vs. 388 nM p < 0.05), IL-6 ( 10.1 vs. 4.4 pg/ml, p < 0.01), ET-1 (2.8 vs.. 1.7 pg/ml, p < 0.01) and CRP ( 11.6 vs. 2.7 mg/L p = 0.02) after 30 days of anakinra treatment. The percent changes in the above markers were greater after anakinra treatment compared to prednisolone treatment (IL-6: −61% vs. −41 %, MDA: −33% vs. +3 % NT: −50 % vs. +0,5%, CRP: −80% vs. −58 %, ET-1: −40% vs. −22%, FMD: 47% vs. −14%, CFR: 35% vs. −4%, AD: +45% vs. +2%, p < 0.05 for all comparisons). PWV remained unchanged after 30 days of anakinra treatment.
Conclusions: Chronic IL-1 inhibition improves endothelial function and consequently, coronary and aortic wall function through reduction of nitro-oxidative stress and endothelin. Treatment with IL-1 inhibition is more effective than corticosteroids in improving vascular function.