title: Neutralizing antibodies are associated with a reduction of interferon-β efficacy during the treatment of Japanese multiple sclerosis patients.
abstract: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system.  Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects.  Intramuscular IFN-β 1a and subcutaneous IFN-β 1b are currently available in Japan, but large-scale studies evaluating the prevalence and clinical implications of NAbs against these IFN-β preparations in MS patients have only been performed in Caucasian populations.  NAbs positivity has been reported to be associated with HLA-DRB1 alleles, suggesting that the positivity might differ among populations with distinct genetic backgrounds.  Clinical information and sera were collected from 229 consecutive MS patients treated with IFN-β in 4 centers in Japan.  Sera were tested for NAbs using a luciferase reporter gene assay.  In total, 5.2% of IFN-β-1a-treated patients (4/77) and 30.3% of IFN-β-1b-treated patients (46/152) were positive for Nabs.  The frequency of NAbs was highest in patients treated for 13 to 24 months.  Clinical relapse and contrast-enhancing lesions in the magnetic resonance imaging increased together with NAbs titers in this group.  In conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in Caucasian populations and is associated with an increase in disease activity.  Therefore, routine NAbs testing is recommended also in Asian populations to ensure the early identification of patients who would benefit from a change in therapy.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. douglas.sato@med.tohoku.ac.jp
authors.forename: Douglas Kazutoshi
authors.initials: DK
authors.lastname: Sato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tomizawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Misu
authors.forename: Paul I
authors.initials: PI
authors.lastname: Creeke
authors.forename: Rachel
authors.initials: R
authors.lastname: Farrell
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D044466:Asian People; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D008156:Luciferases; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D016899:Interferon-beta; D008156:Luciferases