Fingolimod therapy in early multiple sclerosis: an efficacy analysis of the TRANSFORMS and FREEDOMS studies by time since first symptom

CNS Neurosci Ther. 2014 May;20(5):446-51. doi: 10.1111/cns.12235. Epub 2014 Mar 31.

Abstract

Aims: The phase 3 TRANSFORMS and FREEDOMS studies established the efficacy of fingolimod in reducing multiple sclerosis (MS) relapses and magnetic resonance imaging lesions compared with intramuscular (IM) interferon (IFN) β-1a and placebo over 12 and 24 months, respectively.

Methods: To investigate the efficacy of fingolimod at the approved 0.5 mg dose in patients early in the MS disease course, post hoc subgroup analyses of TRANSFORMS (n = 272) and FREEDOMS (n = 217) data were conducted in patients who experienced their first MS symptom <3 years before randomization.

Results: Fingolimod 0.5 mg reduced annualized relapse rate by 73.4% (P = 0.0002) versus IFNβ-1a IM and by 67.4% (P < 0.0001) versus placebo in patients with <3 years since first symptom; respective reductions were 45.4% and 51.4% in subgroups of patients with ≥3 years since first symptom. For patients with <3 years since their first symptom, significantly fewer new/newly enlarged T2 lesions were observed with fingolimod versus IFNβ-1a IM (mean number, 1.94 vs. 2.95; P = 0.036) or placebo (4.1 vs. 10.7; P < 0.001); the mean number of gadolinium-enhancing T1 lesions was significantly reduced versus placebo (0.3 vs. 1.1; P < 0.001).

Conclusion: Fingolimod 0.5 mg is highly effective in reducing relapses and MRI activity in patients early in the MS disease course.

Keywords: Early medical intervention; Fingolimod; Interferon β; Pharmacotherapy; Relapse.

Publication types

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

MeSH terms

  • Adult
  • Disease Progression
  • Female
  • Fingolimod Hydrochloride
  • Gadolinium
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / therapeutic use*
  • Interferon beta-1a
  • Interferon-beta / therapeutic use
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging / methods
  • Male
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Propylene Glycols / therapeutic use*
  • Secondary Prevention
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Immunosuppressive Agents
  • Propylene Glycols
  • Interferon-beta
  • Gadolinium
  • Fingolimod Hydrochloride
  • Sphingosine
  • Interferon beta-1a