Quantitative differences in the immunomodulatory effects of Rebif and Avonex in IFN-β 1a treated multiple sclerosis patients

J Neurol Sci. 2011 Aug 15;307(1-2):41-5. doi: 10.1016/j.jns.2011.05.024. Epub 2011 Jun 11.

Abstract

Interferon-β (IFN-β) is a current effective treatment for multiple sclerosis (MS) and exerts its therapeutic effects by down-modulating the systemic immune response and cytokine signaling. In clinical practice there are several formulations of interferon including a low dose of IFN-β 1a formulation of 30 μg IM once weekly (Avonex) and a high dose formulation of 44 μg SC three times weekly (Rebif). Recent studies suggest that Rebif is more efficacious compared to Avonex in preventing relapses and decreasing MRI activity in relapsing remitting MS (RRMS) patients. This study examines whether there are quantitative gene expression changes in interferon-treated RRMS patients that can explain the difference in efficacy and side effects between Rebif and Avonex. Herein, RRMS patients were treated for three months with IFN-β 1a and the levels of plasma cytokines and gene expression in peripheral blood mononuclear cells were examined. Thirty-two normal subjects were compared to thirty-two RRMS patients, of which ten were treated with Rebif and ten with Avonex. Rebif and Avonex both significantly and equally suppressed plasma TNF-α and IL-6 levels. Rebif suppressed IL-13 significantly more than Avonex. Rebif also significantly suppressed the levels of the chemokines CCL17 and RANTES, the protease ADAM8, and COX-2 at a higher degree compared to Avonex. The STAT1-inducible genes IP-10 and caspase 1 were significantly increased with Rebif compared to Avonex. In conclusion, the higher dosed, more frequently administered IFN-β 1a Rebif when compared to IFN-β 1a Avonex has more potent immunomodulatory effects. These quantitative results might relate to efficacy and side-effect profile of the two IFN-β 1a formulations and provide prospective practical clinical tools to monitor treatment and adjust dosage.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Drug Monitoring / methods
  • Female
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / physiology*
  • Interferon beta-1a
  • Interferon-beta / administration & dosage*
  • Interferon-beta / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / genetics
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Secondary Prevention
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • Adjuvants, Immunologic
  • Immunologic Factors
  • Interferon-beta
  • Interferon beta-1a