title: Natalizumab therapy for highly active pediatric multiple sclerosis.
abstract: OBJECTIVE
  Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pediatric patients with multiple sclerosis (MS).
  
  
  OBJECTIVE
  To report the use of natalizumab in pediatric MS. Natalizumab, a humanized monoclonal antibody targeting α4 integrin, is effective against active relapsing-remitting MS in adults.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Eleven centers for neurology and pediatric neurology in Germany and Austria.
  
  
  METHODS
  A total of 20 pediatric patients with MS who started treatment with natalizumab prior to 18 years of age. These patients underwent magnetic resonance imaging as clinically indicated, despite the fact that 19 of these 20 patients were undergoing first-line disease-modifying therapy. The mean (SD) age at initiation of natalizumab therapy was 16.7 (1.1) years, and the mean (SD) pretreatment period was 18 (10) months.
  
  
  METHODS
  Natalizumab, 300 mg every 4 weeks.
  
  
  METHODS
  Annualized relapse rates, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on magnetic resonance imaging, number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus-antibody status. RESULTS Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 with treatment; P < .02), and mean number of new T2/fluid-attenuated inversion recovery lesions per year (7.8 without treatment vs 0.5 with treatment; P < .001). Two patients developed high-titer neutralizing antibodies against natalizumab and had to stop therapy. Adverse events included headaches, asthenia, infections, and hypersensitivity. Abnormal laboratory results were found for 8 patients. JC virus antibodies were found in 5 of 13 patients. After the discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients within 6 months.
  
  
  CONCLUSIONS
  Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.
authors: Department ofNeurology, Medical University of Vienna, WaehringerGuertel 18-20, A-1090 Vienna, Austria. barbara.bajer-kornek@meduniwien.ac.at
authors: Barbara
authors: B
authors: Kornek
authors: Fahmy
authors: F
authors: Aboul-Enein
authors: Kevin
authors: K
authors: Rostasy
authors: Ruxandra-Iulia
authors: RI
authors: Milos
authors: Irene
authors: I
authors: Steiner
authors: Johann
authors: J
authors: Penzien
authors: Kerstin
authors: K
authors: Hellwig
authors: Kalliopi
authors: K
authors: Pitarokoili
authors: Karin
authors: K
authors: Storm van's Gravesande
authors: Michael
authors: M
authors: Karenfort
authors: Astrid
authors: A
authors: Blaschek
authors: Andreas
authors: A
authors: Meyer
authors: Rainer
authors: R
authors: Seidl
authors: Diana
authors: D
authors: Debelic
authors: Karl
authors: K
authors: Vass
authors: Daniela
authors: D
authors: Prayer
authors: Wolfgang
authors: W
authors: Kristoferitsch
authors: Antonios
authors: A
authors: Bayas
mesh_terms: D000293:Adolescent; D000740:Anemia / Q000139:chemically induced; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001317:Austria; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D039441:Integrin alpha4 / Q000276:immunology; D016899:Interferon-beta / Q000627:therapeutic use; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D000069442:Natalizumab; D012189:Retrospective Studies; D055502:Secondary Prevention
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D039441:Integrin alpha4; D016899:Interferon-beta; D008775:Methylprednisolone