title: Alternative laronidase dose regimen for patients with mucopolysaccharidosis I: a multinational, retrospective, chart review case series.
abstract: Enzyme replacement therapy (ERT) with laronidase (recombinant human α-L-iduronidase, Aldurazyme®) is indicated for non-neurological signs and symptoms of mucopolysaccharidosis type I (MPS I). The approved laronidase dose regimen is weekly infusions of 0.58mg/kg, however, patients and caregivers may have difficulty complying with the weekly regimen. We examined clinical outcomes, tolerability, compliance, and satisfaction in a series of patients who switched to every other week infusions.
  
  
  
  This multinational, retrospective, chart review case series analyzed data from 20 patients who had undergone ERT with laronidase 0.58mg/kg weekly for more than one year, and who then switched to 1.2mg/kg every other week.
  
  
  
  The majority of patients had attenuated MPS I phenotypes (9 with Hurler-Scheie and 8 with Scheie syndromes) and 3 patients had severe MPS I (Hurler syndrome). Most patients presented with organomegaly (17/20), umbilical and/or inguinal hernia (16/20), cardiac abnormalities (17/20), musculoskeletal abnormalities (19/20), and neurological and/or developmental deficits (15/20). Following laronidase treatment, signs stabilized or improved. No deterioration or reversal of clinical outcome was noted in any patient who switched from the weekly dose of 0.58mg.kg to 1.2mg/kg every other week. There were no safety issues during the duration of every other week dosing. Patient compliance and satisfaction with the dosing regimen were greater with every other week dosing than weekly dosing.
  
  
  
  An alternative dose regimen of 1.2mg/kg laronidase every other week was well tolerated and clinically similar to the standard dose for patients who were stabilized with weekly 0.58 mg/kg for one year or more. When an individualized approach to laronidase therapy is necessary, every other week dosing may be an alternative for patients with difficulty receiving weekly infusions.
authors.affiliation: Instituto Nacional de Saude da Mulher, da Criança e do Adolescente Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil. dafne@iff.fiocruz.br.
authors.forename: Dafne Dain Gandelman
authors.initials: DD
authors.lastname: Horovitz
authors.affiliation: Departamento de Pediatria, Serviço de Genética Médica, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Angelina X
authors.initials: AX
authors.lastname: Acosta
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Alegre, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: 2nd Department of Pediatrics, Comenius University Children´s Hospital, Bratislava, Slovakia.
authors.forename: Anna
authors.initials: A
authors.lastname: Hlavatá
authors.affiliation: 2nd Department of Pediatrics, Comenius University Children´s Hospital, Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Hlavatá
authors.affiliation: Department of Genetic Medicine, Westmead Hospital and Sydney University, Sydney, Australia.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Tchan
authors.affiliation: Instituto Nacional de Saude da Mulher, da Criança e do Adolescente Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Lopes Barth
authors.affiliation: Departamento de Pediatria, Serviço de Genética Médica, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Laercio
authors.initials: L
authors.lastname: Cardoso
authors.affiliation: Departamento de Pediatria, Serviço de Genética Médica, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Emília Katiane
authors.initials: EK
authors.lastname: Embiruçu de Araújo Leão
authors.affiliation: Instituto Nacional de Saude da Mulher, da Criança e do Adolescente Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Esposito
authors.affiliation: Department of Pediatrics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: Sandra Obikawa
authors.initials: SO
authors.lastname: Kyosen
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Alegre, Porto Alegre, Brazil.
authors.forename: Carolina Fischinger Moura
authors.initials: CF
authors.lastname: De Souza
authors.affiliation: Department of Pediatrics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage* / Q000627:therapeutic use*; D007223:Infant; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007068:Iduronidase
keywords: Clinical outcomes; Enzyme replacement therapy; Tolerability; α-L-iduronidase deficiency