title: The role of neutralizing antibodies to interferon-β as a biomarker of persistent MRI activity in multiple sclerosis: a 7-year observational study.
abstract: OBJECTIVE
  During interferon-β (IFN-β) therapy, up to 45 % of patients may develop neutralizing antibodies (NAbs), associated with a decreased efficacy of the drug. We investigated in a real-life setting the impact of NAbs on magnetic resonance imaging (MRI) outcomes in a population of 567 IFN-β-treated relapsing-remitting (RR) multiple sclerosis (MS) patients up to 7 years. We also evaluated NAbs' role as a biomarker of the persistence of MRI disease activity.
  
  
  METHODS
  Patients' sera were tested for NAbs' presence by cytopathic effect (CPE) assay every 6-12 months. MRI scans were performed every 12 months. Generalized hierarchical linear models accounting for within-patient correlation were used to analyze T1 gadolinium-enhancing and new T2 lesions. Moreover, further tests were carried out to assess the overall outcome difference from year 1 to year 7 according to NAb status and the possible interaction between NAb status and time of follow-up.
  
  
  RESULTS
  Seventy-five patients (13.2 %) became NAb positive (NAb+) during the follow-up. Considering T1 gadolinium-enhancing (GD+) lesions, we observed a significantly higher incidence in NAb+ patients (52 %, p = 0.0091). Also for new T2 lesions, we found a higher incidence in NAb+ patients (50 %, p = 0.0075). The negative impact of NAbs on the MRI outcomes considered did not change during the follow-up.
  
  
  CONCLUSIONS
  Our 7-year results show the negative effect of NAbs on MRI measures of disease activity and confirm their role as a surrogate marker of IFN-β treatment efficacy.
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy. damiano.paolicelli@uniba.it.
authors.forename: Damiano
authors.initials: D
authors.lastname: Paolicelli
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Manni
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Iaffaldano
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Lecce
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Onghia
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Iaffaldano
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Trojano
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D016899:Interferon-beta
keywords: Biomarkers; Interferon-β; MRI disease activity; Multiple sclerosis; Neutralizing antibodies; Real life