Risk of cardiovascular disease in patients with multiple sclerosis treated with fingolimod compared to natalizumab: A nationwide cohort study of 2095 patients in Denmark

Mult Scler. 2024 Feb;30(2):184-191. doi: 10.1177/13524585231221415. Epub 2024 Jan 11.

Abstract

Background: Fingolimod may be associated with risk of developing cardiovascular disease (CVD). Studies including reference groups and long follow-up are scarce.

Objectives: We hypothesized that patients treated with fingolimod would be at higher risk of developing CVD compared to patients treated with natalizumab.

Methods: A nationwide 12-year cohort study linking individual-level data from the Danish Multiple Sclerosis Registry with health registries on 2095 adult patients with multiple sclerosis (MS) without any health records of CVD at follow-up start. Exposure to fingolimod and natalizumab was defined by the first treatment of at least 3 months. Cohort entry was from 2011 to 2018. We defined CVD as a composite measure, including hypertension, ischemic heart disease, atrial fibrillation, heart failure, and stroke. We used multivariable adjusted Cox regression.

Results: There were 28.8 and 17.4 CVD events per 1000 person-years in fingolimod and natalizumab groups, respectively. Compared to natalizumab-treated patients, fingolimod-treated patients had a higher risk of CVD (hazard ratio (HR) = 1.57; 95% confidence interval (CI) = 1.18-2.08). Hypertension comprised 200 of 244 CVD events.

Conclusion: We found an increased risk of CVD in patients with MS treated with fingolimod. This increased risk was mainly due to hypertension.

Keywords: CVD; Fingolimod; adverse events; cardiovascular disease; multiple sclerosis; safety.

MeSH terms

  • Adult
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Cohort Studies
  • Denmark / epidemiology
  • Fingolimod Hydrochloride / adverse effects
  • Humans
  • Hypertension*
  • Immunosuppressive Agents / adverse effects
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / epidemiology
  • Multiple Sclerosis, Relapsing-Remitting*
  • Natalizumab / adverse effects

Substances

  • Fingolimod Hydrochloride
  • Natalizumab
  • Immunosuppressive Agents