title: Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis.
abstract: BACKGROUND
  Currently available disease-modifying therapies (DMTs) are known to be only partially effective in adults with multiple sclerosis (MS). Little is known about pediatric patients with MS who experience refractory disease while receiving first-line DMTs.
  
  
  OBJECTIVE
  To assess the occurrence and management of refractory disease in a group of pediatric patients with MS treated with first-line DMTs approved for adult patients within a network of pediatric MS centers in the United States.
  
  
  METHODS
  A multicenter, retrospective, longitudinal, open-label study design involving record review of 258 patients with pediatric-onset MS (68.6% female; mean [SD] age at disease onset, 13.2 [3.5] years; range of age at onset, 2.0-17.9 years) who were seen at 6 pediatric MS centers in the United States.
  
  
  METHODS
  We evaluated medication changes owing to refractory disease in cases of pediatric-onset MS.
  
  
  METHODS
  Disease stability as represented by lack of medication change for breakthrough disease.
  
  
  RESULTS
  Records of 258 children with a confirmed diagnosis of MS and exposure to DMTs were reviewed. Interferon beta (prescribed to 200 of 258 children [77.5%]) and glatiramer acetate (prescribed to 53 of 258 children [20.5%]) were the 2 most frequently used first-line DMTs. Overall, 144 children (55.8%) continued receiving 1 therapy, while 65 (25.2%), 29 (11.2%), and 20 (7.8%) received 2, 3, or 4 or more sequential therapies, respectively, during a mean (SD) observation period of 3.9 (2.8) years. Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%). Hispanic children were more likely to experience breakthrough disease while receiving first-line DMTs than non-Hispanic children.
  
  
  CONCLUSIONS
  Although switching between first-line DMTs may be effective in pediatric patients with disease that is refractory to initial treatment, a subset of patients may require second-line therapeutic interventions.
authors.affiliation: Pediatric Multiple Sclerosis and Demyelinating Disorders Center of the Jacobs Neurological Institute, Women and Children’s Hospital of Buffalo, NY 14222, USA. ann.yeh@sympatico.ca
authors.forename: E Ann
authors.initials: EA
authors.lastname: Yeh
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Krupp
authors.forename: Jayne
authors.initials: J
authors.lastname: Ness
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Nancy
authors.initials: N
authors.lastname: Kuntz
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Anita
authors.initials: A
authors.lastname: Belman
authors.forename: Dorothee
authors.initials: D
authors.lastname: Chabas
authors.forename: Mark P
authors.initials: MP
authors.lastname: Gorman
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.forename: John Robert
authors.initials: JR
authors.lastname: Rinker
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy*; D000069442:Natalizumab; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007136:Immunoglobulins; D000069442:Natalizumab; D016899:Interferon-beta