HDL-cholesterol elevation associated with fingolimod and dimethyl fumarate therapies in multiple sclerosis

Abstract

Background: Patients with Multiple Sclerosis (PwMS) display altered lipoproteins levels and function, which seem to affect disease risk and progress. Whether disease-modifying therapies affect the lipoprotein profile in PwMS has scarcely been studied.

Objective: The study aims to assess whether fingolimod and dimethyl fumarate (DMF) affect lipoproteins in PwMS.

Methods: We compared retrospectively the blood lipoprotein levels of 29 fingolimod-treated and 41 DMF-treated patients before and after 3 and 12 months of therapy. Patients treated with cholesterol-reducing medications were not included. Data on weight change and disease activity during 1-year follow-up were obtained.

Results: HDL level, HDL/LDL ratio and HDL/total cholesterol ratio were increased in both treatment groups after 3 months' therapy and sustained, with no change in LDL or triglycerides. While at baseline only 26% of patients met the recommended minimum of HDL 60 mg/dl, after 3 months' therapy, 43% of fingolimod-treated and 47% of DMF-treated patients reached the recommended level. The majority of patients had no weight reduction.

Conclusions: Fingolimod and DMF therapies are associated with a specific increase in HDL in PwMS. Further studies are required to validate these findings and their potential implication as biomarker of reduced inflammatory state and/or reduced risk of neurodegeneration or cardiovascular comorbidity.

Keywords: Biomarker; HDL; dimethyl fumarate; fingolimod; lipoproteins; multiple sclerosis, atherosclerosis.

Figure 1.

Lipoprotein profile of PwMS. The lipoprotein profile of 29 fingolimod-treated patients (a) and 41 DMF-treated patients (b) after 3 and 12 months of therapy was compared with pre-treatment. I–HDL, II–LDL, III–Total cholesterol (TC), IV–Triglycerides (TG). V–ratio HDL/LDL from baseline to 1 year. VII–ratio HDL/TC from baseline to 1 year. Presented is Bonferonni corrected p-values. FTY: fingolimod; DMF: dimethyl fumarate; m: months. Broken line presents recommended minimum level (I), or recommended maximum level (II–IV).

Figure 2.

(a) HDL in patients with active versus stable disease. HDL level at baseline (I) or ratio HDL 3 months/baseline (II) in fingolimod- or DMF-treated patients with active disease versus stable disease. Broken line presents recommended minimum level (I), or no difference after 3 months compared with baseline (II). (b) Majority of patients do not experience weight loss after drug initiation. The weight change (increase, loss, no change or unknown) in patients during 1 year from drug initiation assessed retrospectively, presented as percentage of patients.