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

Abstract

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.

Keywords

azathioprine interferon-β methylprednisolone multiple sclerosis neutralizing antibodies treatment

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