title: Age-dependent effects on the treatment response of natalizumab in MS patients.
abstract: BACKGROUND
  Natalizumab is approved for treatment of active forms of relapsing-remitting multiple sclerosis (MS) based on a pivotal phase III study comprising patients aged 18-50 years. The effect of natalizumab has not been specifically studied in older patients.
  
  
  OBJECTIVE
  We analyzed age-dependent effects on treatment-related outcome measures in 1872 patients, 189 of whom were aged 50 or more, included in the Swedish post-marketing natalizumab surveillance program.
  
  
  METHODS
  In three MS centers registry data for patients aged >50 years were validated.
  
  
  RESULTS
  At baseline older patients had longer disease duration, higher Expanded Disability Status Scale (EDSS) and lower Symbol Digit Modality Test (SDMT) scores than younger patients. The influence from natalizumab on outcome measures was significantly reduced and 18.7% of patients >50 years stopped treatment for lack of effect compared to 7.7% in the younger age group. At baseline, the cerebrospinal fluid levels of the chemokine CXCL13 and the leukocyte cell count were negatively correlated with age in a smaller subgroup of patients.
  
  
  CONCLUSIONS
  These results were in agreement with previous findings suggesting that inflammation is more pronounced in younger patients and therefore the beneficial effects of potent anti-inflammatory treatments are subsiding with older ages.
authors.affiliation: Karolinska University Hospital, Sweden henrik.matell@karolinska.se.
authors.forename: Henrik
authors.initials: H
authors.lastname: Matell
authors.affiliation: Sahlgrenska University Hospital, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
authors.affiliation: Clinical Neuroscience, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
authors.affiliation: Karolinska University Hospital, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Holmén
authors.affiliation: Karolinska University Hospital, Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.affiliation: Karolinska University Hospital, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.affiliation: Karolinska University Hospital, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Karolinska University Hospital, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000328:Adult; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D000069442:Natalizumab; D017063:Outcome Assessment, Health Care; D012042:Registries; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: Natalizumab; antibodies; biomarker; monoclonals/therapeutic use; multiple sclerosis; product surveillance; prognosis