A dose-optimization trial of laronidase (Aldurazyme (R)) in patients with mucopolysaccharidosis I

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dc.contributor.author Giugliani, Roberto
dc.contributor.author Rojas, Veronica Munoz
dc.contributor.author Martins, Ana Maria [UNIFESP]
dc.contributor.author Valadares, Eugnia R.
dc.contributor.author Clarke, Joe T. R.
dc.contributor.author Goes, Jose E. C.
dc.contributor.author Kakkis, Emil D.
dc.contributor.author Worden, Mary Alice
dc.contributor.author Sidman, Marisa
dc.contributor.author Cox, Gerald F.
dc.date.accessioned 2016-01-24T13:52:04Z
dc.date.available 2016-01-24T13:52:04Z
dc.date.issued 2009-01-01
dc.identifier http://dx.doi.org/10.1016/j.ymgme.2008.10.009
dc.identifier.citation Molecular Genetics and Metabolism. San Diego: Academic Press Inc Elsevier Science, v. 96, n. 1, p. 13-19, 2009.
dc.identifier.issn 1096-7192
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/31173
dc.description.abstract Recombinant human alpha-L-iduronidase (Aldurazyme (R) laronidase) is approved as an enzyme replacement therapy to treat the lysosomal storage disorder, mucopolysaccharidosis type I (MPS I) at a dose of 0.58 mg/kg by once-weekly intravenous infusion. To assess whether alternate dosing regimens might provide a better reduction in lysosomal storage, a 26-week, randomized, open-label, multinational dose-optimization trial was conducted. the pharmacodynamic effect and safety of the approved laronidase dose was compared to three alternative regimens (1.2 mg/kg every 2 weeks; 1.2 mg/kg every week; 1.8 mg/kg every 2 weeks) among 33 MPS I patients. the four treatment regimens showed no significant differences in the reduction of urinary glycosaminoglycan excretion or liver volume. Laronidase had an acceptable safety profile in all dose regimen groups. Infusion-associated reactions were the most common drug-related adverse events across dose regimens (by patient incidence), and included pyrexia (21%), vomiting (15%), rash (15%), and urticaria (12%). Patients in the approved dose group had the lowest incidence of drug-related adverse events (38% vs. 63-75%) and infusion-associated reactions (25% vs. 25-63%). There was one death: a patient with acute bronchitis died of respiratory failure 6h after completing the first laronidase infusion. the approved 0.58 mg/kg/week laronidase dose regimen provided near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. the 1.2 mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown. (C) 2008 Elsevier Inc. All rights reserved. en
dc.description.sponsorship BioMarin Pharmaceutical Inc.
dc.description.sponsorship Genzyme Corporation
dc.format.extent 13-19
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Molecular Genetics and Metabolism
dc.rights Acesso restrito
dc.subject Mucopolysaccharidosis (MPS) type I en
dc.subject Hurler en
dc.subject Hurler-Scheie en
dc.subject Scheie en
dc.subject Laronidase en
dc.subject Clinical trial en
dc.subject Dose-optimization en
dc.subject Glycosaminoglycans en
dc.subject Enzyme replacement therapy en
dc.title A dose-optimization trial of laronidase (Aldurazyme (R)) in patients with mucopolysaccharidosis I en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Univ Fed Rio Grande do Sul
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade Federal de Minas Gerais (UFMG)
dc.contributor.institution Hosp Sick Children
dc.contributor.institution Hosp Infantil Joana de Gusmao
dc.contributor.institution BioMarin Pharmaceut Inc
dc.contributor.institution Genzyme Corp
dc.contributor.institution Harvard Univ
dc.description.affiliation Univ Fed Rio Grande do Sul, Postgrad Program Med Sci Pediat, Med Genet Serv HCPA, Dept Genet, Porto Alegre, RS, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Ctr Genet Med, São Paulo, Brazil
dc.description.affiliation Univ Fed Minas Gerais, Dept Propedeut Complementar, Belo Horizonte, MG, Brazil
dc.description.affiliation Hosp Sick Children, Toronto, ON M5G 1X8, Canada
dc.description.affiliation Hosp Infantil Joana de Gusmao, Pediat Intens Care Unit, Florianopolis, SC, Brazil
dc.description.affiliation BioMarin Pharmaceut Inc, Novato, CA USA
dc.description.affiliation Genzyme Corp, Cambridge, MA USA
dc.description.affiliation Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
dc.description.affiliation Harvard Univ, Sch Med, Div Genet, Childrens Hosp Boston, Boston, MA 02115 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Ctr Genet Med, São Paulo, Brazil
dc.identifier.doi 10.1016/j.ymgme.2008.10.009
dc.description.source Web of Science
dc.identifier.wos WOS:000262731900003


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