title: A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis.
abstract: BACKGROUND
  A new liquid formulation of Avonex (interferon beta-1a [IFNbeta-1a]) in a prefilled syringe has been developed to make administration of the drug easier for patients with multiple sclerosis (MS). This formulation does not contain human serum albumin (HSA), often added to interferon (IFN) products for stabilization. However, formulation changes may alter the secondary, tertiary, and quaternary structures of IFNbeta products. These kinds of structural changes could lead to the formation of antibodies directed against IFNbeta. Some of these anti-IFN antibodies may neutralize the biologic activity of IFNbeta.
  
  
  OBJECTIVE
  This study was designed to determine the immunogenicity and safety of the new prefilled syringe (liquid) HSA-free formulation of Avonex in patients with relapsing MS.
  
  
  METHODS
  This was a multicenter, single-arm, open-label study. Patients with relapsing MS received liquid, HSA-free Avonex 30 microg by IM injection from a prefilled syringe once weekly for up to 24 months. Immunogenicity and safety were assessed every 3 months. Serum levels of neutralizing antibodies (NAbs) were measured at baseline and every 3 months using a 2-step enzyme-linked immunosorbent assay and antiviral cytopathic effect assay.
  
  
  RESULTS
  A total of 153 patients (121 women, 32 men; mean [SD] age, 39.6 [9.9] years; age range, 19.0-59.0 years) were enrolled in the study. Sera were available for analysis from 125 and 119 patients after 18 and 24 months of treatment, respectively. By 18 months, 1 patient (1%) had > or =2 consecutive titers of > or =20, a level at which the persistent presence of NAbs has been shown in some studies to have clinical consequences. By 24 months, 1 additional patient (total 2%) had > or =2 consecutive titers of > or =20. At 18 months, 5 patients (4%) had > or =1 NAb titer of > or =5; at 24 months, 6 patients (5%) had > or =1 NAb titer of > or =5. The safety profile of liquid Avonex was comparable to the lyophilized form containing HSA.
  
  
  CONCLUSIONS
  The prefilled syringe (liquid) HSA-free formulation of Avonex was well tolerated and showed a low level of immunogenicity. Over 24 months, 2% of patients developed persistent NAbs (> or =2 consecutive titers of > or =20).
authors.affiliation: Multiple Sclerosis Center at Texas Neurology, Baylor University Medical Center, 6301 Gaston Avenue, Suite 400 West Tower, Dallas, TX 75214, USA. JTPhillips@TexasNeurology.com
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.forename: George
authors.initials: G
authors.lastname: Rice
authors.forename: Elliot
authors.initials: E
authors.lastname: Frohman
authors.forename: Luc
authors.initials: L
authors.lastname: Vande Gaer
authors.forename: Thomas
authors.initials: T
authors.lastname: Scott
authors.forename: Judith
authors.initials: J
authors.lastname: Haas
authors.forename: Eric
authors.initials: E
authors.lastname: Eggenberger
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.forename: William
authors.initials: W
authors.lastname: Stuart
authors.forename: Luis
authors.initials: L
authors.lastname: Cunha
authors.forename: Lawrence
authors.initials: L
authors.lastname: Jacobs
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
authors.forename: Douglas
authors.initials: D
authors.lastname: Arnold
authors.forename: T Jock
authors.initials: TJ
authors.lastname: Murray
authors.forename: Mary
authors.initials: M
authors.lastname: DiBiase
authors.forename: Vijay
authors.initials: V
authors.lastname: Jethwa
authors.forename: Susan
authors.initials: S
authors.lastname: Goelz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D004209:Disposable Equipment; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D013594:Syringes
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a