Efficacy and safety of fingolimod in Hispanic patients with multiple sclerosis: pooled clinical trial analyses

Adv Ther. 2014 Oct;31(10):1072-81. doi: 10.1007/s12325-014-0154-4. Epub 2014 Sep 23.

Abstract

Introduction: The disease characteristics of multiple sclerosis (MS) appear to differ between Hispanic and Caucasian patients, with Hispanic patients having a younger age at onset, and a higher prevalence of optic nerve and spinal cord involvement. Fingolimod, the first-in-class oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing MS, has been shown to significantly reduce annualized relapse rates (ARRs), lesion-based magnetic resonance imaging (MRI) activity, confirmed disability, and brain volume loss, compared with placebo or intramuscular interferon beta-1a (IFNβ-1a IM) in randomized, double-blind, controlled clinical studies. Here, the efficacy and safety profile of fingolimod in Hispanic patients was compared to that observed in the overall study populations.

Methods: This was a post hoc analysis of relapses and safety data for Hispanic patients with relapsing-remitting MS (RRMS) randomized to receive daily fingolimod 0.5 mg, weekly IFNβ-1a IM (30 mg) or placebo, in the phase 3, controlled FREEDOMS, FREEDOMS II, and TRANSFORMS fingolimod studies. The ARR was estimated for each treatment group; only relapses that were confirmed by an independent examining neurologist were included in these analyses. Safety assessments included the incidence of adverse events and serious adverse events.

Results: Eligible Hispanic patients aged 18-55 years (n=181) had been treated as follows: fingolimod 0.5 mg (n=89), IFNβ-1a IM (n=65), and placebo (n=27). Hispanic patients treated with fingolimod for up to 2 years had lower ARRs (ARR: 0.22, 95% confidence interval [CI]: 0.14-0.35) than those receiving placebo (ARR: 0.46, 95% CI: 0.24-0.88) or IFNβ-1a IM (ARR: 0.34, 95% CI: 0.18-0.63), with relative reductions of 52% and 35%, respectively. A transient decrease in heart rate that started to attenuate 6 h after fingolimod administration was observed, consistent with the well-characterized pharmacologic effect following fingolimod treatment initiation. No cases of symptomatic bradycardia were reported in Hispanic patients. The incidence of first-degree atrioventricular block was low and similar across all treatment groups (3.1-4.5%). The safety profile of fingolimod in Hispanic patients was consistent with that reported in the overall population of each study.

Conclusion: Overall, this study demonstrates that fingolimod is efficacious and well tolerated in Hispanic patients with RRMS.

Trial registration: ClinicalTrials.gov NCT00289978 NCT00340834 NCT00355134.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Drug Monitoring
  • Female
  • Fingolimod Hydrochloride* / administration & dosage
  • Fingolimod Hydrochloride* / adverse effects
  • Hispanic or Latino
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interferon beta-1a / administration & dosage
  • Interferon beta-1a / adverse effects
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / ethnology
  • Secondary Prevention
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Fingolimod Hydrochloride
  • Interferon beta-1a

Associated data

  • ClinicalTrials.gov/NCT00289978
  • ClinicalTrials.gov/NCT00340834
  • ClinicalTrials.gov/NCT00355134