title: Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: A double-blind, randomized controlled trial and open-label pharmacokinetic study.
abstract: BACKGROUND
  Natalizumab, an anti-α4 integrin monoclonal antibody, has demonstrated efficacy in phase 2 and 3 studies of predominantly Caucasian patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  OBJECTIVE
  To evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of natalizumab in Japanese RRMS patients.
  
  
  METHODS
  This multicenter, phase 2 study included an open-label PK/PD study in 12 patients (part A) and a double-blind, placebo-controlled, randomized (computer-generated sequence) study in 94 patients (part B). For part B, patients received intravenous natalizumab 300mg (n=47) or placebo (n=47) every 4 weeks. The primary efficacy endpoint was the rate of development of new active lesions (gadolinium-enhancing or new/enlarging T2 lesions) over 24 weeks. Clinical relapses and safety were also assessed.
  
  
  RESULTS
  New active lesions developed at a significantly lower mean rate in natalizumab-treated patients (0.06 lesions/24 weeks) than in placebo-treated patients (0.35 lesions/24 weeks) (p<0.001). The annualized relapse rate was 0.53 for natalizumab and 1.73 for placebo (p<0.001). Twice as many natalizumab-treated patients (79%) as placebo-treated patients (38%) were relapse-free (p<0.001). The safety, PK, and PD profiles of natalizumab in this study were consistent with data in Caucasian RRMS patients.
  
  
  CONCLUSIONS
  In Japanese RRMS patients, natalizumab treatment every 4 weeks for 24 weeks was well tolerated and reduced the development of new brain lesions and relapses (Funded by Biogen; ClinicalTrials.gov identifier: NCT01440101).
authors.affiliation: Kansai Multiple Sclerosis Center and 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 Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Kira
authors.affiliation: Hakusuikai Hatsuishi Hospital, Chiba, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kishida
authors.affiliation: National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.affiliation: Biogen Japan, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sudo
authors.affiliation: Biogen Japan, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ogiwara
authors.affiliation: Biogen Japan, Tokyo, Japan.
authors.forename: J T
authors.initials: JT
authors.lastname: Tibung
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Lucas
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Japanese; Multiple sclerosis; Natalizumab; Pharmacokinetics; Randomized clinical trial