Outcomes of Long-Term Treatment with Laronidase in Patients with Mucopolysaccharidosis Type I

J Pediatr. 2016 Nov;178:219-226.e1. doi: 10.1016/j.jpeds.2016.08.033.

Abstract

Objective: To evaluate long-term outcomes of laronidase enzyme replacement therapy in patients with attenuated mucopolysaccharidosis type I.

Study design: Retrospective analyses of case notes, laboratory results, and data from clinical trials were used to evaluate urinary glycosaminoglycans, forced vital capacity (FVC), 6-minute walk test (6MWT), height-for-age Z score, cardiac valve function, corneal clouding, and visual acuity in 35 patients with attenuated mucopolysaccharidosis type I (Hurler-Scheie and Scheie syndromes) for up to 10 years following the initiation of laronidase therapy.

Results: Statistically significant (P < .001) reductions in mean urinary glycosaminoglycan levels relative to baseline were observed 6 months after treatment initiation and were sustained throughout follow-up. Disease remained stable after treatment initiation with no statistically significant changes in mean FVC, 6MWT, or height-for-age Z score. At last assessments, mitral and aortic valve function remained stable in 65% (22/34) of patients; corneal clouding remained stable in 78% (18/23); visual acuity remained stable in 33% (8/24) and improved in 42% (10/24) of patients. Younger patients (<10 years at treatment initiation) maintained disease measures closer to norms for age for FVC, 6MWT, and height and showed fewer deteriorations in mitral and aortic valve disease and corneal clouding compared with patients aged ≥10 years at treatment initiation.

Conclusion: Laronidase treatment resulted in disease stabilization in the majority of patients with a mean follow-up of 6.1 years. Data suggest that early treatment may result in better outcomes.

Keywords: MPS I; enzyme replacement therapy; laronidase; mucopolysaccharidosis type I.

MeSH terms

  • Child
  • Child, Preschool
  • Enzyme Replacement Therapy / methods*
  • Exercise Test
  • Female
  • Follow-Up Studies
  • Glycosaminoglycans / urine
  • Humans
  • Iduronidase / therapeutic use*
  • Male
  • Mucopolysaccharidosis I / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • Visual Acuity
  • Vital Capacity

Substances

  • Glycosaminoglycans
  • Iduronidase