Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

Abstract

Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-α (P = 0.01). Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

The Impact of Biologics and Tofacitinib on Cardiovascular Risk Factors and Outcomes in Patients with Rheumatic Disease: A Systematic Literature Review

“…Data on patients with RA treated with etanercept were obtained from three RCTs (two full-length articles [ 27 , 44 ] and one conference abstract [ 30 ]), five PCs (all full-length articles) [ 35 , 45 – 48 ], and five RCs (four full-length articles [ 38 , 49 – 51 ] and two conference abstracts [ 19 , 52 ]). Treatment with etanercept increased HDL-C [ 45 , 47 , 48 ] but had no significant effect on LDL-C or TG [ 45 , 47 ].…”

“…Data on patients with RA treated with etanercept were obtained from three RCTs (two full-length articles [ 27 , 44 ] and one conference abstract [ 30 ]), five PCs (all full-length articles) [ 35 , 45 – 48 ], and five RCs (four full-length articles [ 38 , 49 – 51 ] and two conference abstracts [ 19 , 52 ]). Treatment with etanercept increased HDL-C [ 45 , 47 , 48 ] but had no significant effect on LDL-C or TG [ 45 , 47 ]. Etanercept had a favorable effect on lipid profile based on a significantly lower ApoB:ApoA-1 ratio, but primarily in patients exhibiting good or moderate response [ 47 ] according to the European League Against Rheumatism (EULAR) criteria [ 11 ]; however, TC was increased significantly in these patients, whereas there was no statistical difference in EULAR non-responders or in other studies [ 27 , 48 ].…”

“…Treatment with etanercept increased HDL-C [ 45 , 47 , 48 ] but had no significant effect on LDL-C or TG [ 45 , 47 ]. Etanercept had a favorable effect on lipid profile based on a significantly lower ApoB:ApoA-1 ratio, but primarily in patients exhibiting good or moderate response [ 47 ] according to the European League Against Rheumatism (EULAR) criteria [ 11 ]; however, TC was increased significantly in these patients, whereas there was no statistical difference in EULAR non-responders or in other studies [ 27 , 48 ]. Arterial stiffness [ 30 ], AIx [ 27 , 30 , 45 , 46 ], Disease Activity Score-28 (DAS28) [ 45 ], CAVI [ 27 , 30 ], CRP [ 27 , 45 , 46 , 48 ], and left ventricle mass index [ 45 ] were reduced significantly in patients treated with etanercept.…”

“…Etanercept had a favorable effect on lipid profile based on a significantly lower ApoB:ApoA-1 ratio, but primarily in patients exhibiting good or moderate response [ 47 ] according to the European League Against Rheumatism (EULAR) criteria [ 11 ]; however, TC was increased significantly in these patients, whereas there was no statistical difference in EULAR non-responders or in other studies [ 27 , 48 ]. Arterial stiffness [ 30 ], AIx [ 27 , 30 , 45 , 46 ], Disease Activity Score-28 (DAS28) [ 45 ], CAVI [ 27 , 30 ], CRP [ 27 , 45 , 46 , 48 ], and left ventricle mass index [ 45 ] were reduced significantly in patients treated with etanercept. Small increases in CV-associated serious adverse events (SAEs) such as HF, coronary artery disease, MI, and cerebrovascular events were reported in patients with diabetes mellitus and/or chronic pulmonary disease as co-morbidities [ 44 ].…”

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

“…These and other studies have demonstrated improvements in HDL-C metabolism. Interestingly, the majority, but not all (Rodriguez-Jimenez et al, 2014), reports showed that treatment with etanercept also decreased the concentration of TNF-α (van Eijk et al, 2009;Charles-Schoeman et al, 2016). It is possible that the effect of etanercept on HDL-C metabolism was exerted via the SAA mechanism (van Eijk et al, 2009).…”