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

• Published in: Journal of neurology 2013-06, Vol.260 (6), p.1562-1568
• Main Authors: Paolicelli, D., D’Onghia, M., Pellegrini, F., Direnzo, V., Iaffaldano, P., Lavolpe, V., Trojano, M.
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Antibodies, Neutralizing - blood; Disease Progression; Female; Humans; Immunologic Factors - therapeutic use; Interferon-beta - therapeutic use; Male; Medicine; Medicine & Public Health; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; Neuroradiology; Neurosciences; Original Communication; Recurrence; Risk Factors; Time Factors; Treatment Outcome
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-012-6829-3

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.