Original articleEffects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis
Introduction
In patients with established rheumatoid arthritis (RA) mortality is higher than in the general population with cardiovascular disease being the most common cause of death [1], [2]. There is also documented evidence of an increased incidence of non-fatal cardiovascular events in RA [3], [4]. In patients with RA, proinflammatory cytokines produced by the rheumatoid synovium can diffuse within the bloodstream, where they may alter the function of numerous tissues including fat, skeletal muscle, the liver, and the vascular endothelium [5]. These functional alterations can induce changes, such as insulin resistance, increased oxidative stress, endothelial dysfunction, and dyslipidemia that promote atherogenesis [5]. Atherogenic lipid abnormalities have been reported in patients with active RA [6], [7], [8]. RA is characterized by low HDL-cholesterol levels accompanied by an increase in the atherogenic index (total cholesterol/HDL-cholesterol) [6], [7], [9]. Lipid profile usually returns to normal when control of the joint disease is achieved [6], [10]. Medications used to treat the disease can alter lipid levels. Antimalarials improve the lipid profile, increasing HDL-cholesterol and decreasing LDL-cholesterol levels [11]. The effects of TNF-α antagonists on lipids are controversial [10]. In the present study, we investigated the pattern of lipid profile before and after anti-TNF-α treatment.
Section snippets
Methods
In this prospective study, we included 29 patients with RA who fulfilled American College of Rheumatology criteria and in whom an anti-TNF-α therapy was initiated. Twelve patients were begun on adalimumab (40 mg every other week), 11 on infliximab (3 mg/kg on 0, 2, 6 and 8 weeks) and 6 on etanercept (25 mg twice weekly). Fasting blood samples were collected before the first administration of an anti-TNF-α and at 14 weeks after the start of treatment.
All blood samples were taken after an overnight
Results
The population is composed of 26 women, mean age 56 ± 10 years, and 3 men, mean age 70 ± 8 years. Rheumatoid factor was positive in 65% of the patients and anti-CCP antibodies in 70%. Twenty-five patients had erosive disease, 20 patients were on methotrexate (mean dose 13 ± 3 mg) and 7 on other DMARDs [leflunomide (n = 5), hydroxychloroquine (n = 1), D-penicillamine (n = 1)]. Twenty patients were receiving corticosteroids (mean dose 8 ± 3 mg) at the start of the study and all but one maintained a stable dose.
Discussion
In this study, we failed to observe modification of the lipid profile after 14 weeks of anti-TNF therapy in patients with active RA. Results from the literature are conflicting. One study showed an improvement in the lipid pattern, another a progression towards an atherogenic profile and in three others, there was no significant effect on the atherogenic index.
Popa assessed the lipid profile before and 2 weeks after the first dose of adalimumab (n = 33) or placebo (n = 13) in patients with active
References (18)
- et al.
Statins in rheumatology
Joint Bone Spine
(2006) - et al.
Effect of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study
Am J Med
(2002) - et al.
Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis
Clin Chim Acta
(2006) - et al.
Accelerated atherosclerosis. An extraarticular feature of rheumatoid arthritis?
Arthritis Rheum
(2002) - et al.
The mortality of rheumatoid arthritis
Arthritis Rheum
(1994) - et al.
High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors
Arthritis Rheum
(2001) - et al.
Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis
Circulation
(2003) - et al.
Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis
Circulation
(2003) - et al.
Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis
Ann Rheum Dis
(2003)
Cited by (61)
Cardiac Effects of Antirheumatic Drugs
2017, Handbook of Systemic Autoimmune DiseasesCitation Excerpt :Among metabolic effects, most anti-TNFs influence lipid profile but not the TC/HDL-C atherogenic index (AI) (Robertson et al., 2013; Kerekes et al., 2014; Choy et al., 2014). In most studies, short-term infliximab treatment of RA or SpA patients variably influenced HDL-C, LDL-C, TC, and TG levels; however, AI remained unchanged in all these studies (Kiortsis et al., 2006; Vis et al., 2005; Tam et al., 2007; Seriolo et al., 2006; Soubrier et al., 2008; Daien et al., 2012; Damjanov et al., 2014; Popa et al., 2005; 2007b). Adalimumab treatment resulted in significantly increased HDL-C levels, while LDL-C and TG levels did not change (Popa et al., 2005).
Purification, structure features and anti-atherosclerosis activity of a Laminaria japonica polysaccharide
2015, International Journal of Biological MacromoleculesCitation Excerpt :Ohta et al. demonstrated that TNF-α−/−/apoE−/− mice exhibited smaller size of atherosclerotic lesion and lower expression levels of ICAM-1, VCAM-1 and MCP-1 in the aortic sinus than those of apoE−/− mice, suggesting TNF-α plays an atherogenic role by upregulating the expression of ICAM-1, VCAM-1 and MCP-1 in the vascular wall [37]. Anti-TNF-α therapy has been applied to the treatment or reduction of cardiovascular events by attenuation of chronic inflammation, without changing plasma TC, TG, LDL-C and HDL-C levels [38]. IL-1β was reported to be a prototypic inflammatory cytokine that predominantly secreted by macrophages and dendritic cells [39].
Coenzyme Q<inf>10</inf> supplementation in patients with rheumatoid arthritis: Are there any effects on cardiovascular risk factors?
2015, European Journal of Integrative MedicineCitation Excerpt :Diffused proinflammatory cytokines from synovium to systemic circulation, along with resultant C-reactive protein (CRP) may modify the metabolic function of muscles, liver and adipose tissues. These modifications give rise to insulin resistance, lipoprotein abnormalities, oxidative stress and endothelial dysfunction [7]. CRP could be a useful biomarker of systemic and vascular inflammation and could be used as a predictor for CVD [8,9].
Hypertrigyceridemia during infliximab therapy
2014, Joint Bone SpineHypertriglyceridemia and infliximab treatment
2014, Revue du Rhumatisme (Edition Francaise)Lipid profile and anti-tnf-&alpha; use
2013, Revista Brasileira de Reumatologia