Effect of IL-6 Receptor Blockade on Proprotein Convertase Subtilisin/Kexin Type-9 and Cholesterol Efflux Capacity in Rheumatoid Arthritis Patients

Abstract

The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 [median % change 32 (3–141), p=0.021]. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.

Proprotein Convertase Subtilisin/Kexin Type 9 in the Inflammation-Related Dyslipidemia of Patients with Axial Spondyloarthritis is Related to Disease Activity.

“…This result may be of potential interest since the effect of anti-TNF therapy on PCSK9 has not previously been studied. This finding was not observed in a series of 27 patients with rheumatoid arthritis treated with tocilizumab during one year (37). However, in this series, variations in LDL cholesterol over the year of study correlated directly with changes in PCSK9 serum concentration.…”

Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis

“…Eleven longitudinal studies met the inclusion criteria. Nine studies reported data for both BMI and weight [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], while one only reported on weight [ 32 ] and one only on BMI [ 33 ]. Hence, each meta-analysis for weight and BMI included 10 studies.…”

HDL cholesterol efflux capacity and concentration in patients with rheumatoid arthritis: a systematic review and meta-analysis

“…However, the epidemiological data that have been used to explore the association between CEC and RA are inconsistent. Some of the previous studies have shown that the CEC is signi cantly lower in RA patients than in healthy controls, but others have failed to reach conclusions [24][25][26][27][28][29][30][31][32][33].…”