Biological Therapies and Lipid Profile

Lotta Ljung, Solbritt Rantapää-Dahlqvist
European Musculoskeletal Review, 2011;6(4):240-247
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Abstract

The prevention of cardiovascular disease (CVD) is of major concern when considering patients with inflammatory rheumatic disease. Biological therapeutic agents have improved the quality of life of patients, but their side effects are a concern. Since tumour necrosis factor-inhibitors have been approved for clinical usage, their effects on lipid levels have been analysed in a number of studies of both short and long duration. These studies show a consistent trend towards increased levels of total cholesterol and high-density lipoprotein cholesterol, as well as an increase in the levels of triglycerides. However, the results of the lipid ratios are more inconsistent. Whether changes in the lipid profile are beneficial or, on the contrary, carry risk of CVD is still unclear. Treatment with interleukin 6 receptor inhibitor has been observed to increase lipid levels and manufacturers recommend that lipid abnormalities should be monitored during treatment. In this article, published data on the effects of biological therapy on lipids and lipid levels are reviewed and discussed in relation to duration of therapy and CVD prevention, mainly in rheumatoid arthritis.
Keywords
Biological therapy, dyslipidaemia, cardiovascular disease, rheumatoid arthritis, inflammatory rheumatic disease, tumour necrosis factor
Disclosure The authors have no conflicts of interest to declare
Received: October 03, 2011 Accepted October 24, 2011
Correspondence: Solbritt Rantapää-Dahlqvist, Department of Public Health and Clinical Medicine, Rheumatology University Hospital S-901 85 Umeå, Sweden.E: solbritt.rantapaa.dahlqvist@medicin.umu.se

Cardiovascular disease (CVD) is a major cause of morbidity in patients suffering from inflammatory rheumatic disease 1–3 and, in the field of clinical rheumatology, an increasing interest in the prevention of CVD has become noticeable in recent years among researchers and clinicians alike. The relationship between raised plasma cholesterol and atherosclerotic CVD fulfils the criteria for causality in the general population, and the evidence showing that lowering plasma cholesterol reduces the risk of CVD is solid. 4 In inflammatory rheumatic disease, the traditional CVD risk factors alone are insufficient to explain the high prevalence of atherosclerosis; the impact of dyslipidaemia, however, is measurable. 5,6.

This article gives an overview of the relationship between treatment with biological drugs and the lipid profile of patients with inflammatory rheumatic disease; it will focus mainly on the treatment of rheumatoid arthritis (RA), since most studies concern this disease, and to a lesser extent on the treatment of psoriatic arthritis (PsoA) and ankylosing spondylitis (AS).

The studies on tumor necrosis factor (TNF)-inhibitors discussed in this overview are primarily from the clinical setting and comprise cohort studies either with or without controls, in contrast to the studies on interleukin 6 (IL-6) receptor inhibition, which are all randomised controlled trials (RCTs). Studies on other biological drugs are scarce or lack information with respect to the effects of these drugs on plasma lipid measurements.

Plasma Lipids, Cardiovascular Risk and Inflammation
The lipids in the circulating blood plasma are transported attached to apolipoproteins forming lipoproteins. Total cholesterol is mainly carried in low-density lipoproteins (LDLs), and the concentration of LDL correlates with that of total cholesterol as well as with the risk of CVD.7 Among the other lipoproteins, intermediate-density lipoproteins (IDLs) and small particles of very-low-density lipoproteins (VLDLs) are atherogenic, while high-density lipoproteins (HDLs) are athero protective. Triglycerides are transported as major components of non-atherogenic chylomicrons and large particles of VLDLs, but are also components of atherogenic IDLs and small VLDLs. The association between triglyceride concentration and risk of CVD is weaker than that between LDL and risk of CVD. Several other CVD risk factors (e.g., dietary habits, diabetes, insulin resistance, abdominal obesity, smoking and alcohol consumption) are associated with the level of triglycerides, making extensive adjustments necessary when evaluating study results.7–9

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