title: Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis.
abstract: BACKGROUND
  The clinical impact of neutralizing antibodies against interferon-beta (NAb) is controversial. Their presence can lead to a decrease in interferon-beta (IFNβ) efficacy. Fatigue reported in patients with multiple sclerosis (MS) may be associated with an unfavorable clinical course. We conducted a prospective multicentre study to assess the association between response to IFNβ, NAb and fatigue.
  
  
  METHODS
  Patients with relapsing-remitting MS on IFNβ treatment were included. During the second year of treatment, the patients were analyzed for NAb status and non-response criteria to IFNβ (number of relapses ≥1 during the follow-up period, increase in the Expanded Disability Status Scale ≥0.5). The score on the Modified Fatigue Impact Scale (MFIS pathological if score ≥35) was noted for each patient.
  
  
  RESULTS
  Of the 176 patients included: 22.3% were NAb positive, 54.5% presented non-response criteria to IFNβ, and 57.4% had a pathological MFIS score. Fatigue was increased in NAb + patients (p = 0.0014) and they were more likely to present non-response criteria to IFNβ (p = 0.041) than NAb- patients. Multivariate logistic regression analysis showed that the presence of NAb was related to fatigue (p = 0.0032) and denoted disease activity in these patients (p = 0.026).
  
  
  CONCLUSIONS
  This study demonstrates the impact of NAb on the non-clinical response to IFNβ. Fatigue assessment is an indicator of IFNβ responsiveness and a predictive biomarker of deterioration on patient's neurological status.
authors.forename: Philippe
authors.initials: P
authors.lastname: Manceau
authors.forename: Clotilde
authors.initials: C
authors.lastname: Latarche
authors.forename: Sophie
authors.initials: S
authors.lastname: Pittion
authors.forename: Gilles
authors.initials: G
authors.lastname: Edan
authors.forename: Jérôme
authors.initials: J
authors.lastname: de Sèze
authors.forename: Catherine
authors.initials: C
authors.lastname: Massart
authors.forename: Marc
authors.initials: M
authors.lastname: Debouverie
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D005221:Fatigue / Q000209:etiology*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D016899:Interferon-beta