Effects of Treatment with Adalimumab on Blood Lipid Levels and Atherosclerosis in Patients with Rheumatoid Arthritis

Abstract

BackgroundTreatment with tumor necrosis factor inhibitors for rheumatoid arthritis has been associated with a decreased risk of cardiovascular disease in observational studies. There are conflicting data on the influence of tumor necrosis factor inhibitors on lipid levels.ObjectivesTo evaluate the effect of treatment with adalimumab on blood lipid levels, lipoproteins, and atherosclerosis of the carotid artery.MethodsFourteen patients with active rheumatoid arthritis (11 women and 3 men; mean age 63.7 years; median disease duration 9.0 years; and 78% rheumatoid factor positive) were treated with adalimumab 40 mg subcutaneously every 2 weeks and followed for 3 months. The patients had not been treated with adalimumab previously and had not received other tumor necrosis factor inhibitors within the past 3 months or moderate/high dose corticosteroids within the past 2 weeks. The intima-media thickness of the common carotid artery was assessed using B mode ultrasonography. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol levels were analyzed in fresh fasting blood samples, whereas apolipoprotein B and apolipoprotein A1 (apoA1) levels were determined in thawed plasma samples using standard turbidimetric immunoassays.ResultsTotal cholesterol (mean = 5.36 vs 5.96 mmol/L; P = 0.005), LDL cholesterol (mean = 3.33 vs 3.77 mmol/L; P = .005), HDL cholesterol (mean = 1.43 vs 1.55 mmol/L; P = 0.048), apolipoprotein B (mean = 1.04 vs 1.13 g/L; P = .012), and apoA1 (mean = 1.42 vs 1.58 g/L; P = 0.005) all increased, but there were no major changes in the LDL to HDL cholesterol ratio (median = 2.56 vs 2.35; P = 0.27) or the apolipoprotein B to apoA1 ratio (mean = 0.76 vs 0.74; P = 0.46). There was no change in triglyceride levels (P = 0.55). Disease activity decreased significantly from baseline to the 3-month evaluation (disease activity score based on 28 joints mean = 5.6 vs 4.1; P = 0.007). An increase in apoA1 correlated with decreases in the patient global assessment of disease severity (r = 0.79; P = 0.001) and C-reactive protein level (r = 0.74; P = 0.003). Changes in the apoliprotein B to apoA1 ratio correlated with changes in erythrocyte sedimentation rate (r = 0.54; P = 0.046). There was no major change in the common carotid artery intima-media thickness (mean = 0.78 vs 0.80 mm; P = 0.48).ConclusionsAlthough these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery.

Improvements in High-Density Lipoprotein Quantity and Quality Contribute to the Cardiovascular Benefits by Anti-tumor Necrosis Factor Therapies in Rheumatoid Arthritis: A Systemic Review and Meta-Analysis

“…Following TNF inhibition, the increase in HDL and ApoA1 is usually more significant in those responsive to TNF blockade (24,52,60,62), corresponding to the fact that those responders gain more prominent CVDs benefits (8), suggesting a role of decreased systemic inflammation following anti-TNF therapies in the observed CVDs benefits. Currently, we cannot analyze the association between treatment response and lipid changes due to insufficient data.…”

Genetic Predisposition and Inflammatory Inhibitors in COVID-19: Where Do We Stand?

“…Although increased levels of TNF-α have been revealed in various types of cytokine storms, no significant benefit was observed considering the treatment of the phenomenon. Etanercept, Adalimumab, and Infliximab have to be administered as soon as possible from the onset of symptoms since delayed therapy may reduce the efficacy of these agents [ 68 , 69 ]. Although no studies have been completed, preliminary data show that it could be used to treat mild COVID-19 pneumonia to reduce IL-1 and IL-6 levels as possible endpoints [ 68 , 69 ].…”

Inflammatory Mechanisms in COVID-19 and Atherosclerosis: Current Pharmaceutical Perspectives

“…Similarly, tocilizumab has been shown to increase endothelial activity and decrease aortic stiffness in atherosclerotic patients [ 81 , 82 , 83 ], with lower levels of CRP and fibrinogen observed [ 86 , 87 , 88 ]. A 17 mg/dL rise in low-density lipoprotein (LDL) has been noted, while another analysis reported a 22% increase in LDL and total cholesterol as well as a 48% increase in fasting triglycerides in these patients [ 89 ]. These results point to the need for further drug evaluation and more cautious patient selection.…”