Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis

Mult Scler. 2009 Mar;15(3):323-8. doi: 10.1177/1352458508099476. Epub 2008 Nov 21.

Abstract

Background: It is unknown whether immunosuppression of patients who have developed interferon-beta (IFN-beta) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood.

Objective: We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-beta bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-beta.

Methods: We included 13 patients with MS with NAbs and a low IFN-beta bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-beta. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction.

Results: A total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group.

Conclusion: Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-beta bioactivity in NAb-positive patients with MS.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Antibodies / blood
  • Azathioprine / administration & dosage*
  • Drug Resistance / immunology
  • Drug Therapy, Combination
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / immunology
  • Genes, Reporter
  • Glucocorticoids / administration & dosage*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Interferon-beta / immunology*
  • Interferon-beta / therapeutic use
  • Methylprednisolone / administration & dosage*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Myxovirus Resistance Proteins
  • RNA, Messenger / metabolism
  • Treatment Failure

Substances

  • Antibodies
  • Glucocorticoids
  • Immunosuppressive Agents
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • Interferon-beta
  • GTP-Binding Proteins
  • Azathioprine
  • Methylprednisolone