title: The impact of neutralizing antibodies on the risk of disease worsening in interferon β-treated relapsing multiple sclerosis: a 5 year post-marketing study.
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.
authors: Department of Neurosciences and Sense Organs, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors: D
authors: D
authors: Paolicelli
authors: M
authors: M
authors: D'Onghia
authors: F
authors: F
authors: Pellegrini
authors: V
authors: V
authors: Direnzo
authors: P
authors: P
authors: Iaffaldano
authors: V
authors: V
authors: Lavolpe
authors: M
authors: M
authors: Trojano
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D007155:Immunologic Factors; D016899:Interferon-beta