title: Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease.
abstract: OBJECTIVE
  A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease.
  
  
  METHODS
  Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid alpha-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort.
  
  
  RESULTS
  At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid alpha-glucosidase; no patients withdrew from the study because of safety concerns.
  
  
  CONCLUSIONS
  In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence.
authors.affiliation: Division of Pediatric Endocrinology, Diabetology and Metabolism, Hôpital Debrousse, University Lyon, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.forename: Barry
authors.initials: B
authors.lastname: Byrne
authors.forename: J Edmund
authors.initials: JE
authors.lastname: Wraith
authors.forename: Nancy
authors.initials: N
authors.lastname: Leslie
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.forename: Georgianne L
authors.initials: GL
authors.lastname: Arnold
authors.forename: Eniko K
authors.initials: EK
authors.lastname: Pivnick
authors.forename: C J
authors.initials: CJ
authors.lastname: Ottinger
authors.forename: Peter H
authors.initials: PH
authors.lastname: Robinson
authors.forename: John-Charles A
authors.initials: JC
authors.lastname: Loo
authors.forename: Martin
authors.initials: M
authors.lastname: Smitka
authors.forename: Philip
authors.initials: P
authors.lastname: Jardine
authors.forename: Luciano
authors.initials: L
authors.lastname: Tatò
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Shawn
authors.initials: S
authors.lastname: McCandless
authors.forename: Shigemi
authors.initials: S
authors.lastname: Kimura
authors.forename: L
authors.initials: L
authors.lastname: Mehta
authors.forename: Deeksha
authors.initials: D
authors.lastname: Bali
authors.forename: Alison
authors.initials: A
authors.lastname: Skrinar
authors.forename: Claire
authors.initials: C
authors.lastname: Morgan
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rangachari
authors.forename: Deya
authors.initials: D
authors.lastname: Corzo
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D001827:Body Height; D001835:Body Weight; D002675:Child, Preschool; D003371:Cough / Q000139:chemically induced; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D007074:Immunoglobulin G; D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases