Alternative laronidase dose regimen for patients with mucopolysaccharidosis I: a multinational, retrospective, chart review case series

作者：Gandelman Horovitz Dafne Dain; Acosta Angelina X; Giugliani Roberto; Hlavata Anna; Hlavata Katarina; Tchan Michel C; Barth Anneliese Lopes; Cardoso Laercio Jr; Embirucu de Araujo Leao Emilia Katiane; Esposito Ana Carolina; Kyosen Sandra Obikawa; Moura De Souza Carolina Fischinger; Martins Ana Maria

来源：Orphanet Journal of Rare Diseases, 2016, 11(1): 51.

DOI：10.1186/s13023-016-0437-8

• Enzyme replacement therapy
• alpha-L-iduronidase deficiency
• Clinical outcomes
• Tolerability

Background: Enzyme replacement therapy (ERT) with laronidase (recombinant human alpha-L-iduronidase, Aldurazyme (R)) 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.
Methods: 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.
Results: 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.
Conclusions: 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.

• 出版日期2016-4-29