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Interferon beta preparations for the treatment of multiple sclerosis patients differ in neutralizing antibody seroprevalence and immunogenicity

Department of Clinical Neuroscience, Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

U Rot

Department of Neurology, Medical Center, Ljubljana, Slovenia

M Suoniemi

Department of Clinical Neuroscience, Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

F Deisenhammer

Department of Neurology, Innsbruck Medical University, Austria

J Hillert

Department of Clinical Neuroscience, Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

A Fogdell-Hahn

Department of Clinical Neuroscience, Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden, anna.fogdell-hahn{at}ki.se

Development of neutralizing antibodies (NAbs) reduces the clinical efficacy of interferon beta (IFNß) treatment in multiple sclerosis (MS) patients. The aim of this study was to evaluate NAb seroprevalence (frequency of patients with NAbs) and immunogenicity (titer levels) of IFNß preparations in a clinical setting. We analysed 1115 consecutive MS patients, treated with one of the three available IFNß preparations, for an average of 40 months (1-120 months), for the presence of NAbs with the MxA protein induction assay. Overall, 32% of patients were positive for NAbs with neutralizing titers above 10. The frequency of NAbs, ie, the seroprevalence, was 13% in Avonex-treated patients, 43% for Betaferon, 39% for Rebif22 and 30% for Rebif44. In addition, the potential to induce high titer levels, ie, the immunogenicity, was observed to differ between preparations. Avonex, showing the lowest seroprevalence, also showed low immunogenicity and typically induced low titers. Betaferon, showing the highest seroprevalence when inducing NAbs, induced lower titers compared to Rebif22 and Rebif44. Treatment duration over five years only marginally correlated with decreased seroprevalence and titer levels.

In conclusion, NAbs to IFNß are common in a clinical setting and the IFNß preparations differ not only in NAb seroprevalence, but also in immunogenicity.

Key Words: immunogenicity • interferon beta • multiple sclerosis • neutralizing antibodies • seroprevalence

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