title: High-dose intravenous interferon-beta in multiple sclerosis patients with high-titer neutralizing antibodies (HINABS II) - A pilot study.
abstract: BACKGROUND
  Neutralizing antibodies (NAb) against interferon-beta (IFNβ) affect its treatment efficacy. So far, there are no anti-NAb strategies available.
  
  
  OBJECTIVE
  To investigate if the repeated administration of high-dose IFNβ-1b intravenous in NAb positive multiple sclerosis (MS) patients induces tolerance and establishes IFNβ bioavailability as measured by the induction of myxovirus protein A (MxA).
  
  
  METHODS
  Nine MS patients with NAb titers >500 10-fold reduction units (TRU) received 1500μg IFNβ-1b intravenously once weekly over three months. Blood samples were collected at screening, monthly during the treatment period (before and four hours after IFNβ administration), and at follow-up after 6 months for determination of NAbs and MxA expression.
  
  
  RESULTS
  Median NAb titer at baseline was 1429TRU. NAb titers determined before each infusion did not significantly change over the treatment period and were not different at follow-up compared to baseline. However, NAb titers were significantly decreased four hours after IFNβ infusions (by roughly 50%) and MxA mRNA levels were significantly elevated reaching a median value of 206.
  
  
  CONCLUSIONS
  Weekly intravenous administration of IFNβ in patients with high NAb titers established its bioavailability, but failed to induce tolerance towards IFNβ.
authors: Innsbruck Medical University, Department of Neurology, Anichstraße 35, 6020 Innsbruck, Austria. Electronic address: harald.hegen@i-med.ac.at.
authors: H
authors: H
authors: Hegen
authors: Allgemeines Krankenhaus Linz, Department of Neurology, Krankenhausstraße 9, 4021 Linz, Austria.
authors: M
authors: M
authors: Guger
authors: Paracelsus Medical University, Department of Neurology, Ignaz-Harrer-Straße 79, 5020 Salzburg, Austria.
authors: A
authors: A
authors: Harrer
authors: Innsbruck Medical University, Department of Neurology, Anichstraße 35, 6020 Innsbruck, Austria.
authors: M
authors: M
authors: Hoelzl
authors: Paracelsus Medical University, Department of Neurology, Ignaz-Harrer-Straße 79, 5020 Salzburg, Austria.
authors: J
authors: J
authors: Kraus
authors: Landesklinikum Horn, Department of Neurology, Spitalgase 10, 3580 Horn, Austria.
authors: A
authors: A
authors: Skrobal
authors: Landeskrankenhaus Villach, Department of Neurology, Nikolaigasse 43, 9500 Villach, Austria.
authors: F
authors: F
authors: Schautzer
authors: Allgemeines Krankenhaus Linz, Department of Neurology, Krankenhausstraße 9, 4021 Linz, Austria.
authors: S
authors: S
authors: Schmidegg
authors: Innsbruck Medical University, Department of Radiology, Anichstraße 35, 6020 Innsbruck, Austria.
authors: M
authors: M
authors: Schocke
authors: Innsbruck Medical University, Department of Neurology, Anichstraße 35, 6020 Innsbruck, Austria.
authors: F
authors: F
authors: Deisenhammer
keywords: Bioavailability; Immune tolerance; Interferon-beta (IFNβ); Multiple sclerosis (MS); Myxovirus protein A (MxA); Neutralizing antibody (NAb)