Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1

Pediatrics. 2008 Dec;122(6):1182-90. doi: 10.1542/peds.2007-2144.

Abstract

Objective: The goal was to analyze the clinical responses to enzyme replacement therapy with alglucerase or imiglucerase in a large international cohort of children with Gaucher disease type 1.

Methods: Anonymized data from 884 children in the International Collaborative Gaucher Group Gaucher Registry were analyzed to determine the effects of long-term enzyme replacement therapy with alglucerase or imiglucerase on hematologic and visceral manifestations, linear growth, and skeletal disease. The parameters measured were hemoglobin levels, platelet counts, spleen and liver volumes, z scores for height and bone mineral density, and reports of bone pain and bone crises.

Results: The median height z score for the study population was -1.4 at baseline. After 8 years of treatment, the median height approximated the median value for the normal population. Anemia, although not severe, was present in >50% of patients at baseline and resolved for all patients after 8 years of treatment. More than 50% of patients had platelet counts of <100000 platelets per mm3 at baseline, but >95% had platelet counts above this level after 8 years of treatment. Liver and spleen volumes decreased over 8 years of treatment. The mean bone mineral density z score was -0.34 at baseline, and values normalized within 6.6 years of treatment. Seventeen percent of patients reported a bone crisis before treatment and in the first 2 years of treatment, but no bone crises were reported after 2 years of enzyme replacement therapy. Few patients (2.5%) without bone crises before enzyme replacement therapy had a crisis after the start of treatment.

Conclusions: These longitudinal data quantitate the benefits of continuous enzyme replacement therapy with alglucerase/imiglucerase for children with Gaucher disease type 1. Within 8 years of enzyme replacement therapy, most clinical parameters studied became normal or nearly normal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Bone Density / physiology
  • Child
  • Child Development / physiology
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Gaucher Disease / diagnosis
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / mortality
  • Glucosylceramidase / administration & dosage*
  • Humans
  • Infant
  • Infant, Newborn
  • International Cooperation
  • Kaplan-Meier Estimate
  • Long-Term Care
  • Male
  • Probability
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome

Substances

  • alglucerase
  • Glucosylceramidase
  • imiglucerase