Современная ревматология (Mar 2016)
Assessment of cardiovascular risk from the use of an interleukin-1 inhibitor in patients with severe tophaceous gout
Abstract
It is suggested that interleukin (IL)-1β inhibition may promote a reduction in the risk of cardiovascular diseases; however, the mechanism of this impact has not been adequately investigated.Objective: to evaluate the impact of canakinumab therapy on the structural and functional properties of the vascular bed and the stiffness of the vessel wall.Patients and methods. An open-labeled prospective study was conducted in 20 patients with chronic tophaceous gout at the V.A. Nasonova Research Institute of Rheumatology. Among the patients, there were 17 (85%) men and 3 (15%) women. All the patents received a single subcutaneous injection of canakinumab 150 mg. Estimation of high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels, 24-hour blood pressure (BP) monitoring, duplex scanning of the carotid arteries (intimamedia thickness (IMT)), and determination of central artery stiffness (aortic pulse wave velocity (APWV), m/sec) were done before and 14 and 120 days after drug administration; the level of hs-CRP was quantitatively measured using a high-sensitivity immunoturbidimetric assay and the concentration of IL-6 was determined by xMAP technology (Human Grp I Cytokine 27-plex panel on a BioPlex-200 analyzer (Bio-Rad, USA). Antihypertensive lipidlowering therapy was not changed during the investigation. Statistical analysis was carried out using a package of applied Statistica 10.0 programs (StatSoft/Inc., USA).Results. Examination of the common carotid artery indicated that the median IMT that was 0.83 [0.71; 0.94] mm at baseline decreased to 0.74 [0.69; 0.84] mm by the end of the investigation (p = 0.022). The median APWV that was 14.12 [10; 17] m/sec at baseline dropped to 13.1 [11; 14] by the end of the investigation, but statistically insignificantly (p = 0.79). By the end of the investigation, there was a reduction in APWV as related to the baseline level in 13 (65%) patients: 7 of them had not one swollen joint and only 5 patients had a CRP level of > 5 mg/l, which was significantly less frequently than that in patients without positive changes in this index: in 6 (86%) of the 7 patients (p = 0.043). There was a direct correlation of changes in APW with those in serum CRP levels (p = 0.012 and p = 0.047, respectively) after 14 and 120 days and with those in serum IL-6 concentrations following 14 days (p = 0.003). 24-hour BP monitoring showed no significant BP change in the patients after 14 and 120 days after injection. The mean level of total cholesterol and triglycerides remained unchanged.Conclusion. The IL-6 inhibitor canakinumab can have a positive effect on IMT and arterial stiffness. The effect of the drug on the structural and functional properties of the vascular bed is due to the magnitude of its anti-inflammatory activity
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