The global impact of imiglucerase therapy in children with Gaucher disease types 1 and 3: a real-world analysis from the International Collaborative Gaucher Group Gaucher Registry

Abstract

Gaucher disease (GD) in children is highly heterogeneous, severe, and particularly devastating in GD type 3 (GD3), which has systemic and neurological involvement. Imiglucerase enzyme replacement therapy is well-established for managing hematovisceral and skeletal manifestations in GD type 1 (GD1). Its long-term impact in GD3 remains underexplored, with evidence limited to small, single-center cohorts and one registry analysis with limited follow-up. This longitudinal analysis used data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of January 2023. Children diagnosed with GD1 or GD3 who started imiglucerase before age 18 years and had an intact spleen and at least one baseline and follow-up measurement were included. Linear mixed models were used to evaluate long-term treatment response of hemoglobin, platelet count, liver and spleen volumes, and Z-scores for height, weight, body mass index, and total lumbar spine bone mineral density (BMD). In total, 961 children with GD1 and 236 with GD3 met the inclusion criteria, representing a population with severe disease requiring early imiglucerase therapy at a median age (25th, 75th percentile) of 7.8 (4.3, 12.0) years for GD1 and 1.9 (1.4, 3.4) years for GD3. Significant hematological and visceral improvements were observed within the first 1.5 years of treatment (p < 0.001 for all parameters), followed by incremental gains during up to two decades. Height Z-scores increased substantially during the first three years of treatment (p < 0.001). Total lumbar spine BMD Z-scores improved (p < 0.05). This is the largest, most comprehensive global evaluation of long-term imiglucerase therapy in pediatric GD1 and GD3. Despite complex disease burden in GD3, imiglucerase therapy led to marked hematovisceral disease reversal and meaningful growth improvements, closely paralleling responses in GD1. These findings emphasize the importance of early diagnosis and sustained treatment to optimize long-term outcomes. NCT00358943 (registration date: April 1, 1991). Not applicable.