title: Efficacy and safety of subcutaneous interferon β-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study.
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.
authors: Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy. destefano@unisi.it
authors: Nicola
authors: N
authors: De Stefano
authors: Maria Pia
authors: MP
authors: Sormani
authors: Bettina
authors: B
authors: Stubinski
authors: Gregg
authors: G
authors: Blevins
authors: Jelena S
authors: JS
authors: Drulovic
authors: Delphine
authors: D
authors: Issard
authors: Penko
authors: P
authors: Shotekov
authors: Claudio
authors: C
authors: Gasperini
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000418:Albumins / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D001284:Atrophy / Q000473:pathology; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005682:Gadolinium; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D055502:Secondary Prevention; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000418:Albumins; D057134:Antibodies, Neutralizing; D012710:Serum Albumin, Bovine; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a