title: Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab.
abstract: BACKGROUND
  In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy.
  
  
  OBJECTIVE
  The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries.
  
  
  METHODS
  We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab.
  
  
  RESULTS
  Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0-5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0-4.0%) and transient in 1.0% (95% CI: 0.7-1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations.
  
  
  CONCLUSIONS
  The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark. pss@rh.regionh.dk
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: Poul Erik Hyldgaard
authors.initials: PE
authors.lastname: Jensen
authors.forename: Aiden
authors.initials: A
authors.lastname: Haghikia
authors.forename: Malin
authors.initials: M
authors.lastname: Lundkvist
authors.forename: Christian
authors.initials: C
authors.lastname: Vedeler
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.forename: Anna
authors.initials: A
authors.lastname: Fogdell-Hahn
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D000069442:Natalizumab
chemical_list: D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4