Assessment of cardiovascular risk from the use of an interleukin-1 inhibitor in patients with severe tophaceous gout

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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