title: Neutralizing antibodies explain the poor clinical response to interferon beta in a small proportion of patients with multiple sclerosis: a retrospective study.
abstract: BACKGROUND
  Neutralizing antibodies (NAbs) against Interferon beta (IFNbeta) are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS) patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNbeta treatment.
  
  
  METHODS
  We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNbeta during the treatment period. Patients were classified as: group A, developing >or= 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNbeta formulations for at least one year. NAbs positivity was defined as NAbs titre >or= 20 TRU.
  
  
  RESULTS
  Seventeen patients (12.1%) were NAbs positive. NAbs positivity correlated with poorer clinical response (p < 0.04). As expected, the prevalence of NAbs was significantly lower in Group C (2.1%) than in Group A (17.0%) and Group B (17.0%). However, in the groups of patients with a poor clinical response (A, B), NAbs positivity was found only in a small proportion of patients.
  
  
  CONCLUSIONS
  The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNbeta.
authors.affiliation: Departments of Neurological Sciences, Sapienza University, Rome, Italy. emilia.sbardella@uniroma1.it
authors.forename: Emilia
authors.initials: E
authors.lastname: Sbardella
authors.forename: Valentina
authors.initials: V
authors.lastname: Tomassini
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bellomi
authors.forename: Luca Ausili
authors.initials: LA
authors.lastname: Cefaro
authors.forename: Vincenzo Brescia
authors.initials: VB
authors.lastname: Morra
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D015415:Biomarkers; D016899:Interferon-beta