title: Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial.
abstract: BACKGROUND
  Efficacy of interferon beta in multiple sclerosis (MS) can be dampened in patients who develop neutralizing antidrug antibodies (NAbs). Peginterferon beta1a is an interferon conjugated with a polyethylene glycol (PEG) moiety. Pegylation increases a drug's half life and exposure, and may also reduce immunogenicity.
  
  
  OBJECTIVE
  The objective of this study was to characterize the incidence and impact of immunogenicity to peginterferon beta1a over 2 years in patients with MS.
  
  
  METHODS
  Patients with relapsing-remitting MS (N = 1512) were randomized to subcutaneous peginterferon beta1a 125 μg every 2 or 4 weeks, or placebo, for 1 year; patients in the placebo group were rerandomized to active treatment in year 2. The incidence and titers of binding antibodies (BAbs) and NAbs to interferon and antibodies to PEG (anti-PEG) were assessed in analytically validated assays. The clinical impact of immunogenicity on relapse and magnetic resonance imaging endpoints was evaluated.
  
  
  RESULTS
  Over 2 years, 6%, less than 1%, and 7% of patients developed anti-interferon BAbs, NAbs, and anti-PEG antibodies, respectively. There was no discernible clinically meaningful effect of antibody status on the pharmacodynamic, efficacy, or safety parameters evaluated, although these analyses were limited by the low incidence of treatment-emergent antibodies.
  
  
  CONCLUSIONS
  The treatment effect of peginterferon beta1a in patients with relapsing-remitting MS is not expected to be attenuated by immunogenicity.
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Joleen T
authors.initials: JT
authors.lastname: White
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Newsome
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.affiliation: Department of Neurology, Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bermel
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Seddighzadeh
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Hung
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Crossman
authors.affiliation: 14 Cambridge Center, Building 6A, Floor 6, Office K01, Cambridge, MA 02142, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
keywords: immunogenicity; neutralizing antibodies; peginterferon beta1a; pegylation; relapsing–remitting multiple sclerosis