Background It is supposed that IL-1β inhibition may be associated with cardiovascular risk reduction [1, 2], but it isn't known what effect of it is on endothelial function.
Objectives To assess canakinumab effects on structural and functional parameters of vasculature.
Methods Open-label prospective study of 20 pts (17 (85%) males and 3 (15%) females) with chronic gout was performed in 2014–2015 y. at the V. A. Nasonova Research Institute of Rheumatology. All patients received one dose of canakinumab 150 mg subcutaneously. Lab parameters (uric acid, cholesterol, triglycerides, hsCRP and interleukin-6 (IL-6) levels), 24 hour BP monitoring, comprehensive Echo-CG, duplex scanning of carotid arteries the intima-media thickness (TIM) measurements of near and far wall were taken from both common carotid arteries (CCA), vascular wall stiffness was evaluated before injection of canakinumab and on days 14 and 120 after. The quantification of serum hsCRP levels was done with highly sensitive immune turbidimetric test, serum IL-6 levels was detected using of “xMAP” technology (Human Grp I Cytokine 27-plex panel) and on the analyzer “BioPlex-200” (Bio-Rad, the USA). Lipid-lowering and antihypertensive therapy was not modified during the study. Statistical analysis was performed using the application package STATISTICA 10.0 (StatSoft.Inc., USA). Differences were considered significant at p<0.05.
Results Baseline TIM in the CCA was 0,83 [0.71; 0.94] mm, while by the end of the study it dropped to 0,74 [0.69; 0.84] mm (p=0.022). Median baseline pulse wave velocity (PWV) in the aorta was 14,12 [10; 17] m/s, dropping during the study to 13,1 [11; 14] (p=0,79). Falling down of baseline arterial stiffness index was documented in 13 (65%) pts, and by the end of the study in 7 out of them not a single joint was tender or swollen, hsCRP levels >5 mg/l was in 5 out of 13 pts, who was statistically significantly more rare as compared to pts without positive changes of this index (in 6 out of 7 pts (86%)) (p=0.043). Median of serum hsCRP level and IL-6 level in pts who had reduction of PWV was significantly smaller then in others pts at 120 days (respectively, hsCRP level – 2.7 [2.3; 7.7] mg/dl vs 11.5 [6.9; 17.7] mg/dl (p=0.0084) and IL-6 level – 5,9 [3,9; 7.7] pg/ml vs 12,6 [10,8; 22,4] pg/ml) (p=0,44). Based on BP monitoring data no changes from baseline BP measured before injection of Canakinumab, and on Day 14 or Day 120, occurred. Mean levels of cholesterol and triglycerides didn't change as well
Conclusions IL-1β inhibitor Canakinumab may have positive effect on TIM parameters. Effects of Canakinumab on arterial stiffness parameters depend on the potency of anti-inflammatory effect.
Ridker P.M., Thuren T., Zalewski A., Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Kanakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011; 162(4):597–605.
M. Ridker, Ridker P.M., Lüscher T. F. Anti-inflammatory therapies for cardiovascular disease DOI: http://dx.doi.org/10.1093/eurheartj/ehu203 1782-1791 First published online: 26 May 2014
Disclosure of Interest None declared