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The impact of neutralizing antibodies on the risk of disease worsening in interferon β–treated relapsing multiple sclerosis: a 5 year post-marketing study

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Abstract

The impact of neutralizing antibodies (NAbs) on interferon β (IFNβ) efficacy in MS patients is still an object of controversy. To evaluate the clinical response to IFNβ during NAb-positive (NAb+) and NAb-negative (NAb−) statuses on a large population of relapsing remitting (RR) MS patients were followed up to 5 years. Sera from 567 RR MS patients treated with IFNβ for 2–5 years were collected every 6–12 months and evaluated for NAb presence by a cytopathic effect assay. The relapse rate and expanded disability status scale (EDSS) score were assessed at baseline and every 6 months for each patient. A NAb+ status was defined after two consecutive positive titers of NAbs >/= 20 neutralizing units (NU)/mL. Multivariate models were used to analyze the relapse rate, the time to first relapse, the time to confirmed EDSS score 4 during NAb+ and NAb− statuses. A propensity score (PS) matching analysis was performed to assess the robustness of the multivariate models. Fourteen percent of patients became NAb+ during the follow-up. A significant increase of the relapse rate (IRR = 1.38; p = 0.0247) and decrease of the time to 1st relapse (IRR = 1.51; p = 0.0111) were found during NAb+ periods. The PS matching analysis, in a selected cohort of patients, demonstrated a negative trend of NAbs on the time to reach the milestone EDSS 4 (IRR = 2.94; p = 0.0879). This long-term post-marketing observational study further confirms that the occurrence of NAbs significantly affects the risk of disease worsening in IFNβ- treated RRMS.

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Conflicts of interest

The authors have the following conflict of interest to declare: Dr Trojano received honoraria for consultancy and/or speaking from Biogen Idec, Sanofi-Aventis, Merck-Serono, Novartis and Bayer-Schering and research grants from Merck-Serono, Biogen Idec, Sanofi-Aventis and Novartis. Dr. Paolicelli received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Bayer-Schering and research grant from Serono Foundation. Dr. Pellegrini has received honoraria from and is a consultant for Biogen Idec.

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This study has been approved by the appropriate ethics committee and has therefore been performed in the accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurosciences and Sense Organs, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124, Bari, Italy

    D. Paolicelli, M. D’Onghia, V. Direnzo, P. Iaffaldano, V. Lavolpe & M. Trojano

  2. Scientific Institute “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, Italy

    F. Pellegrini

Authors
  1. D. Paolicelli
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  2. M. D’Onghia
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  3. F. Pellegrini
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  4. V. Direnzo
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  5. P. Iaffaldano
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  6. V. Lavolpe
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  7. M. Trojano
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Correspondence to M. Trojano.

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Paolicelli, D., D’Onghia, M., Pellegrini, F. et al. The impact of neutralizing antibodies on the risk of disease worsening in interferon β–treated relapsing multiple sclerosis: a 5 year post-marketing study. J Neurol 260, 1562–1568 (2013). https://doi.org/10.1007/s00415-012-6829-3

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  • DOI: https://doi.org/10.1007/s00415-012-6829-3

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