title: Long-term efficacy and safety of intramuscular interferon beta-1a: Randomized postmarketing trial of two dosing regimens in Japanese patients with relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of 2 years of treatment with intramuscular interferon beta-1a (IM IFN beta-1a) in Japanese patients with relapsing-remitting multiple sclerosis, with an exploratory analysis of the impact of initial dose titration on tolerability.
  
  
  METHODS
  Japanese patients with relapsing-remitting multiple sclerosis were randomized to receive IM IFN beta-1a at dosages of either 30mcg once weekly (full-dose group, n=50) or 15mcg once weekly for 2 weeks then 30mcg once weekly thereafter (titration group, n=50). Key outcomes included annualized relapse rate (ARR) at 2 years (primary endpoint), change in disability measured using the Expanded Disability Status Scale (EDSS), safety, and tolerability.
  
  
  RESULTS
  The ARR (95% CI) decreased from 1.540 (1.381-1.718) at baseline to 0.371 (0.240-0.571) at Year 1 and 0.351 (0.244-0.503) at Year 2. EDSS improvements were apparent from Week 24; the mean change from baseline EDSS score (2.1) at Year 2 was -0.34 (P=0.004). The most frequently reported adverse events were influenza-like illness (92%), nasopharyngitis (57%), relapse of multiple sclerosis (51%), and injection-site reaction (30%). The overall incidence and severity of influenza-like symptoms were similar in the full-dose group and titration group; only 1 participant, in the full-dose group (2%), experienced severe influenza-like symptoms. However, the incidence of influenza-like symptoms was slightly reduced at earlier timepoints in the titration group.
  
  
  CONCLUSIONS
  The results of this 2-year study demonstrate that IM IFN beta-1a can be used effectively and safely in Japanese patients with relapsing-remitting multiple sclerosis for an extended period of time.
authors.affiliation: Kansai Multiple Sclerosis Center and Department of Neurology, Kyoto Min-iren Central Hospital, Kyoto, Japan. Electronic address: Saida_takahiko@maia.eonet.ne.jp.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Saida
authors.affiliation: Department of Neurology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. Electronic address: kira@neuro.med.kyushu-u.ac.jp.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kira
authors.affiliation: Biogen Japan Ltd, Tokyo, Japan. Electronic address: yasuhiro.ueno@biogen.com.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Biogen Japan Ltd, Tokyo, Japan. Electronic address: nysharad@gmail.com.
authors.forename: Naozumi
authors.initials: N
authors.lastname: Harada
authors.affiliation: Biogen Japan Ltd, Tokyo, Japan. Electronic address: toshiyuki.hirakata@biogen.com.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hirakata
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000068556:Interferon beta-1a
keywords: Clinical trial; Interferon beta-1a; Japan; Multiple sclerosis; Phase IV