Inhibition of interleukin-6 by tocilizumab improves endothelial glycocalyx and myocardial work index in patients with rheumatoid arthritis

Abstract

Abstract Background/Introduction Tocilizumab, an interleukin-6 receptor blocker is used for the treatment of rheumatoid arthritis (RA). Purpose We investigated the effects of tocilizumab on endothelial glycocalyx and myocardial function in patients with RA. Methods Eighty patients with RA (age: 64±9 years) were randomized to tocilizumab (n=40) or prednisolone (n=40)for 3 months. We measured at baseline and 3 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI), c) global LV longitudinal strain (GLS), longitudinal systolic (LongSr) and diastolic (LongSrE) strain rate, d) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) using speckle tracking imaging. Results At baseline, all patients had similar disease activity score and markers of vascular and myocardial function. Compared with baseline, patients under tocilizumab had reduced PBR (2.14±0.2 vs. 1.97±0.2μm), PWV (11±3 vs. 10.3±2m/s), cSBP (134±18 vs. 129±16mmHg) and LongSrE (0.91±0.3 vs. 1±0.3 1/s) at 3 months (p<0.05). There were no statistically significant differences in the above measured markers in patients under prednisolone (p>0.05) (Table). Compared with prednisolone, tocilizumab treatment achieved a greater increase of GLS (8.5% vs. 2.4%), GWI (12.2% vs. 2.7%), GCW (10.3% vs. 5.9%) and a greater reduction of GWW (−30% vs. −13%) (p<0.05 for all comparisons), despite a similar reduction in C-reactive protein post-treatment. The percent decrease of PBR was associated with the percent decrease of cSBP (r=0.46), PWV (r=0.37) and reversely related with the percent improvement of GLS (r=−0.43) and GWI (r=−0.39) (p<0.05). Conclusions IL-6 inhibition by tocilizumab improves endothelial and vascular function leading to a greater increase of effective myocardial work compared to prednisolone in patients with RA. Funding Acknowledgement Type of funding source: None