Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial

Joleen T. White, Scott Newsome, Bernd C. Kieseier, Robert A. Bermel, Yue Cui, Ali Seddighzadeh, Serena Hung, Mary Crossman, Meena Subramanyam

Research output: Contribution to journalArticle

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. Conclusion: The treatment effect of peginterferon beta1a in patients with relapsing-remitting MS is not expected to be attenuated by immunogenicity.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalTherapeutic Advances in Neurological Disorders
Volume9
Issue number4
DOIs
StatePublished - Jul 1 2016

Keywords

  • immunogenicity
  • neutralizing antibodies
  • peginterferon beta1a
  • pegylation
  • relapsing-remitting multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Pharmacology

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