Efficacy and safety of subcutaneous interferon β-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study

J Neurol Sci. 2012 Jan 15;312(1-2):97-101. doi: 10.1016/j.jns.2011.08.013. Epub 2011 Aug 31.

Abstract

Background: The IMPROVE study demonstrated that the fetal bovine serum (FBS)- and human serum albumin (HSA)-free formulation of subcutaneous (sc) interferon (IFN) beta-1a had beneficial effects on the numbers of combined unique active magnetic resonance imaging (MRI) lesions in relapsing-remitting multiple sclerosis (RRMS). Here we report additional MRI endpoints (including post hoc analyses), and clinical efficacy, safety, and immunogenicity outcomes.

Methods: Patients with active RRMS were randomized (2:1) to IFN beta-1a, 44 mcg sc three times weekly (tiw) (n=120), or placebo (n=60), for 16 weeks (double-blind phase). All patients then received IFN beta-1a, 44 mcg sc tiw, for 24 weeks (rater-blind phase). Patients underwent MRI brain scans every 4 weeks.

Results: Compared with placebo, there was a 68% reduction in the mean cumulative number of new gadolinium-enhancing lesions with IFN beta-1a as early as week 4 (p<0.001), and a 53% reduction in the mean cumulative number of new T2 lesions as early as week 8 (p=0.025; post hoc analyses). During the 16-week double-blind phase, the relapse rate was 0.14 (95% confidence interval [CI] 0.09-0.23) with IFN beta-1a and 0.33 (95% CI 0.22-0.52) with placebo (p=0.010). Safety outcomes were consistent with those expected with IFN-beta treatment.

Conclusions: The FBS/HSA-free formulation of sc IFN beta-1a has a beneficial impact on MRI and efficacy outcomes as early as 4 weeks after treatment initiation in patients with RRMS and has a safety profile consistent with previous trials of sc IFN beta-1a.

Trial registration: ClinicalTrials.gov NCT00441103.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Albumins / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood
  • Atrophy / pathology
  • Cattle
  • Chemistry, Pharmaceutical / methods
  • Gadolinium
  • Humans
  • Injections, Subcutaneous
  • Interferon beta-1a
  • Interferon-beta / administration & dosage*
  • Interferon-beta / adverse effects
  • Interferon-beta / immunology
  • Magnetic Resonance Imaging / methods
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Secondary Prevention
  • Serum Albumin, Bovine / administration & dosage
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Albumins
  • Antibodies, Neutralizing
  • Serum Albumin, Bovine
  • Interferon-beta
  • Gadolinium
  • Interferon beta-1a

Associated data

  • ClinicalTrials.gov/NCT00441103