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.

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BackgroundElevated triglycerides or triglyceride-rich lipoproteins are an additional cause of cardiovascular (CV) disease. Given that patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CV disease and show an altered lipid profile, our objective was to study whether three molecules that play a central role in the triglyceride metabolism: apolipoprotein C-III (ApoC3), angiopoietin-like protein 4 (ANGPLT4), and lipoprotein lipase (LPL) differ between SLE patients and controls, and how they are related to disease characteristics, including disease damage.MethodsCross-sectional study that included 347 women, 185 of them diagnosed with SLE and 162 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in SLE patients and controls. A multivariable analysis was performed to assess whether ANGPTL4, ApoC3 and LPL molecules differ between patients and controls and to study their relationship with SLE disease damage.ResultsAfter fully multivariable analysis that included classic CV risk factors, and the modifications that the disease itself produces over the lipid profile, it was found that ApoC3 was significantly lower (beta coef. -1.2 [95%CI -1.6- -0.8) mg/dl, <0.001), and ANGPTL4 (beta coef. 63 [95%CI 35-90] ng/ml, <0.001) and LPL (beta coef. 79 [95%CI 30-128] ng/ml, p=0.002) significantly higher in patients with SLE compared to controls. Disease damage score was significantly and independently associated with higher serum levels of LPL (beta coef. 23 [95%CI 10-35] ng/ml, p=0.001). Mediation analysis suggested that the relationship between disease damage and LPL was direct and not mediated by ApoC3 or ANGPLT4.ConclusionThe ApoC3, ANGPLT4 and LPL axis is disrupted in patients with SLE. Disease damage explains this disturbance.

Background: Secukinumab has been shown effective for psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA) in randomized trials. The aim of this study was to analyze baseline patient and disease characteristics associated with a better retention rate of secukinumab under real-world conditions.Patients and Methods: Real-life, prospective multicenter observational study involving 138 patients, 61 PsA and 77 AxSpA, who were analyzed at baseline, 6, 12 months and subsequently every year after starting secukinumab regardless of the line of treatment. Demographics and disease characteristics, measures of activity, secukinumab use, and adverse events were collected. Drug survival was analyzed using Kaplan-Meier curves and factors associated with discontinuation were evaluated using Cox regression. The machine-learning J48 decision tree classifier was also applied.Results: During the 1st year of treatment, 75% of patients persisted with secukinumab, but accrued 71% (n = 32) in total losses (n = 45). The backward stepwise (Wald) method selected diagnosis, obesity, and gender as relevant variables, the latter when analyzing the interactions. At 1 year of follow-up, the Cox model showed the best retention rate in the groups of AxSpa women (95%, 95% CI 93–97%) and PsA men (89%, 95% CI 84–93%), with the worst retention in PsA women (66%, 95% CI 54–79%). The J48 predicted secukinumab retention with an accuracy of 77.2%. No unexpected safety issues were observed.Conclusions: Secukinumab shows the best retention rate at 1 year of treatment in AxSpA women and in PsA men, independently of factors such as the time of disease evolution, the line of treatment or the initial dose of the drug.

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