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Optimising MS disease-modifying therapies: antibodies in perspective

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Abstract.

A proportion of people with multiple sclerosis (MS) treated with interferon (IFN) â develop neutralising anti-IFN β antibodies (NABs). The immunogenicity of the available commercial compounds relates to the genetic structure of the IFN β molecule, its mode of production, glycosylation status, aggregate formation, commercial formulation, potency, dose, frequency and, possibly, route of administration. At present, it is not possible to predict who will develop NABs usually appear within the first 2 years of starting therapy. In patients treated with IFN β in whom NABs persist for a significant period of time, their presence is associated with a reduction in both the biological effects and clinical efficacy. Approximately one third of NAB-positive patients with a titre > 20 NU/mL will revert to NAB-negative status with long-term follow-up. The persistence of NABs appears to be linked to the type of IFN β treatment as well as the titre of antibodies. The overall efficacy of IFN β and, hence, of any biological disease-modifying treatment (DMT) would be substantially improved if the development of NABs could be prevented or reversed. Although the overall efficacy of IFN β in MS is relatively modest, the efficacy in individuals who remain NAB-negative is considerably better than in those who become persistently NAB-positive. One could argue that when comparing the ‘true’ clinical efficacy of different IFN β products, the comparisons should be limited to the cohorts that remain NAB-negative. As a corollary, the therapeutic efficacy of IFN β could be maximised if patients who tolerate higher-dose preparations could be prevented from developing persistent NABs. Strategies employed to prevent or reverse the development of NABs with other biological compounds (e. g. insulin, factor VIII, IFN β, recombinant human erythropoietin) include improvements in the manufacturing process, immunosuppression, induction of tolerance and deimmunisation, and these should be considered in relation to biological DMT therapy as part of future clinical studies.

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  1. Department of Neuroinflammation, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

    Gavin Giovannoni

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  1. Gavin Giovannoni
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Correspondence to Gavin Giovannoni.

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Giovannoni, G. Optimising MS disease-modifying therapies: antibodies in perspective. J Neurol 251 (Suppl 5), v30–v35 (2004). https://doi.org/10.1007/s00415-004-1505-x

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  • DOI: https://doi.org/10.1007/s00415-004-1505-x

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