title: Neutralizing antibodies reduce the efficacy of betaIFN during treatment of multiple sclerosis.
abstract: OBJECTIVE
  To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNbeta.
  
  
  METHODS
  This was an open-label study involving 78 patients with multiple sclerosis treated with Betaferon 8 million IU (MIU) subcutaneously (SC) every other day (n = 20), Rebif 22 micro g SC 3 times weekly (n = 25), or Avonex 30 micro g IM once weekly (n = 33). Every 3 months, blood samples were collected and sera were analyzed for NAbs using an antiviral cytopathic effect assay. Patients were categorized according to their NAb status: NAb negative (NAb-); isolated NAb positive (NAb+), patients with > or =1 positive sample (titer > or = 20); and persistent NAb+, patients with > or =2 consecutive positive samples (titer > or = 20). Patients who were NAb- and persistent NAb+ were compared for relapse rate, time between first and second relapse, percentage of relapse-free patients, and percentage of patients who had a sustained progression of > or =1 point on the Expanded Disability Status Scale (EDSS).
  
  
  RESULTS
  The incidence of persistent NAb+ patients was 35% for Betaferon, 20% for Rebif, and 3% for Avonex. During IFNbeta treatment, both NAb+ and NAb- patients showed a reduction in relapse rate; this reduction (25%) was not significant in NAb+ patients but was significant (67%; p < 0.0001) in NAb- patients. In addition, the mean relapse rate was higher (p = 0.039), mean time between first and second relapse was shorter (13 vs 21 months; p = 0.0064), and there was a trend suggesting that NAbs affected the probability of remaining relapse free (p = 0.08). A higher percentage of NAb+ patients versus NAb- patients had worsening of EDSS scores during follow-up (p = 0.013).
  
  
  CONCLUSIONS
  Persistent NAbs significantly reduce the clinical efficacy of IFNbeta.
authors.affiliation: Centro Riferimento Regionale Sclerosi Multipla (CReSM) & Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Malucchi
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.forename: F
authors.initials: F
authors.lastname: Gilli
authors.forename: R
authors.initials: R
authors.lastname: Bottero
authors.forename: A
authors.initials: A
authors.lastname: Di Sapio
authors.forename: M
authors.initials: M
authors.lastname: Capobianco
authors.forename: A
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004351:Drug Resistance; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D009500:Neutralization Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007518:Isoantibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a