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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

¹ The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
² Institute for Inflammation Research (IIR), Rigshospitalet, Copenhagen, Denmark; Biomonitor, Symbion Science Park, Copenhagen, Denmark
³ Biomonitor, Symbion Science Park, Copenhagen, Denmark; Laboratory of Viral Oncology, CNRS FRE2937, Institut Andre Lwoff, 94801 Villejuif, France

^* To whom correspondence should be addressed.

	Abstract

Background

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

Methods

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

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

First published on November 21, 2008, doi:10.1177/1352458508099476

Multiple Sclerosis 2009;15:323.

A more recent version of this article appeared on March 1, 2009


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