Effects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis

doi:10.1016/j.jbspin.2007.04.014

Joint Bone Spine

Volume 75, Issue 1, January 2008, Pages 22-24

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Abstract

Objectives

Analyse the effects of anti-tumor necrosis factor therapy on serum levels of lipid in patients with rheumatoid arthritis (RA).

Methods

Twenty-nine patients (26 females, 3 males) with established RA undergoing anti-TNF therapy (n = 12, adalimumab; n = 11, infliximab; n = 6, etanercept) were recruited. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), and apolipoproteins (apo b and apo a) were assessed at baseline and after 14 weeks of treatment.

Results

The disease activity index score (DAS₂₈) was 5.19 ± 0.90 and decreased to 3.46 ± 0.97 at 16 weeks (p < 0.001). There was no change neither in the levels of TC (5.65 ± 0.98 mmol/l vs 5.78 ± 1.06 mmol/l; p = 0.43), TG (1.40 ± 0.79 mmol/l vs 1.45 ± 0.67 mmol/l; p = 0.59), HDL-C (1.92 ± 0.49 mmol/l vs 1.97 ± 0.49 mmol/l; p = 0.36), apo a1 (1.92 ± 0.28 g/l vs 1.99 ± 0.29 g/l; p = 0.06), and LDL-C (3.41 ± 0.91 mmol/l vs 3.47 ± 0.96 mmol/l; p = 0.66), nor in apo b (1.126 ± 0.302 g/l vs 1.13 ± 0.28 g/l; p = 0.89), atherogenic index (3.13 ± 1.05 vs 3.09 ± 0.89; p = 0.69) or the apo b/apo a1 ratio (0.58 ± 0.25 vs 0.56 ± 0.22; p = 0.33).

Conclusion

The favourable effect of anti-tumor necrosis factor therapy on cardiovascular morbidity is not related to effects on lipid metabolism.

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

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Accelerated atherosclerosis and increased cardio- (CV) and cerebrovascular morbidity and mortality have been associated with rheumatoid arthritis (RA), as well as other inflammatory rheumatic diseases. Sustained systemic inflammation may be the major driver of atherogenesis. Aspirin, statins, folic acid, angiotensin-converting enzyme inhibitors, and angiotensin II blockers have been introduced to the prevention and therapy of vascular diseases in RA. Nonsteroidal antiinflammatory drugs (NSAIDs), primarily COX-2 inhibitors may increase CV risk; therefore, we should be cautious when prescribing these compounds. There may be differences among the various NSAIDs. Corticosteroids may exert both beneficial and detrimental effects on the vasculature. The antiinflammatory action of NSAIDs and corticosteroids may override their potential atherogenic nature. Antimalarials and methotrexate have been found to be cardioprotective in most studies. Leflunomide may not increase atherosclerosis but it can cause hypertension. Biologics, primarily tumor necrosis factor alpha inhibitors, effectively suppress arthritis and they have various effects on the vascular system. Increased lipid levels observed in the case of all biologics may be explained by the “lipid paradox.” Biologics may also have beneficial effects on other metabolic markers. In most trials, anti-TNF biologics have been associated with reduced CV risk. More data are needed on rituximab, tocilizumab, and abatacept, as well as tofacitinib. In addition to atherosclerosis, heart failure, arrhythmias, and hypertension should also be considered when administering antirheumatic drugs. In the clinical practice, European League Against Rheumatism and other recommendations may guide the rheumatologist how to prevent and manage CV comorbidities in rheumatic patients.
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60 days supplementation with 100 mg/day CoQ₁₀ showed some indication of a reduction in body weight and LDL but overall no meaningful improvement was seen in CVD risk factors. Studies with larger number of patients, longer follow up and higher doses of the supplement may provide evidence of effectiveness.
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O uso do anti-TNF alfa tem sido associado a várias alterações no perfil lipídico, embora o estudo dessas alterações tenha gerado resultados que ainda são conflitantes. O conhecimento desse fato é de grande importância quando se observa a associação entre doenças reumáticas e aterogenêse acelerada. Esta pesquisa foi feita com o intuito de verificar alterações no perfil lipídico de usuários de anti-TNF-α na população do sul do Brasil e sua associação com tempo de uso, indicações, gênero do paciente e tipo de anti-TNF. Para tanto, analisaram-se os perfis de colesterol total (TC), HDL colesterol (HDLc), LDL colesterol (LDLc), índice aterogênico (IAT) e triglicerídeos (TGs) de 58 pacientes (42 com artrite reumatoide e 16 com espondiloartrites) antes e depois do uso desse medicamento por um tempo mediano de 16,0 meses. Não se observaram alterações nos níveis de CT, HDLc, LDLc e IAT (P = NS). Todavia, houve um aumento significativo nos níveis de TGs (P = 0,03). A diferença mediana dos valores de TGs entre primeira e segunda medidas foi de 16 mg/dL, e esse aumento não estava associado ao gênero do paciente, tempo de uso, indicação de uso ou tipo de anti-TNF-α (P = NS). Concluiu-se que o uso de anti TNF-α está associado com aumento nos valores de TGs.
The use of anti-TNF-α has been associated with several changes in lipid profile, although some study results are conflicting. The knowledge of this fact is of great importance when one observes at the association between rheumatic diseases and accelerated atherogenesis. The aim of this analysis was search for changes in lipid profile in anti TNF-α users in the population of Southern Brazil and its association with duration of use, indications, patient gender and type of anti-TNF. For this purpose, we studied the profiles of total cholesterol (TC), HDL cholesterol (HDLc), LDL cholesterol (LDLc), atherogenic index (ATI) and triglycerides (TGs) of 58 patients (42 with rheumatoid arthritis and 16 with spondyloarthritis) before and after using this drug for a median of 16.0 months. There were no changes in the levels of TC, HDLc, LDLc and ATI (P = NS). However, there was a significant increase in TG levels (P = 0.03). The median difference between first and second TG measurements was 16 mg/dL and this increase was not associated with gender, time of use, use indication or type of anti TNF-α (P = NS). It was concluded that the use of anti TNF-α is associated with increased values of TG.

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Original articleEffects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis

Abstract

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Joint Bone Spine

Am J Med

Clin Chim Acta

Accelerated atherosclerosis. An extraarticular feature of rheumatoid arthritis?

Arthritis Rheum

The mortality of rheumatoid arthritis

Arthritis Rheum

High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors

Arthritis Rheum

Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis

Circulation

Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis

Circulation

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis

Ann Rheum Dis

Original article
Effects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis