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

The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark mads.ravnborg{at}ouh.regionsyddanmark.dk

K Bendtzen

Institute for Inflammation Research (IIR), Rigshospitalet, Copenhagen, Denmark; Biomonitor, Symbion Science Park, Copenhagen, Denmark

O Christensen

Institute for Inflammation Research (IIR), Rigshospitalet, Copenhagen, Denmark; Biomonitor, Symbion Science Park, Copenhagen, Denmark

PEH Jensen

The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

D Hesse

The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

MG Tovey

Biomonitor, Symbion Science Park, Copenhagen, Denmark; Laboratory of Viral Oncology, CNRS FRE2937, Institut Andre Lwoff, 94801 Villejuif, France

PS Sørensen

The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Background

It is unknown whether immunosuppression of patients who have developed interferon-β (IFN-β) 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-β bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-β.

Methods

We included 13 patients with MS with NAbs and a low IFN-β 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-β. 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-β bioactivity in NAb-positive patients with MS.

Key Words: azathioprine • interferon-β • methylprednisolone • multiple sclerosis • neutralizing antibodies • treatment

This version was published on March 1, 2009

Multiple Sclerosis, Vol. 15, No. 3, 323-328 (2009)
DOI: 10.1177/1352458508099476


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