TY - JOUR
T1 - Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment
AU - for the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigators
AU - Weinreb, Neal J.
AU - Camelo, José Simon
AU - Charrow, Joel
AU - McClain, Monica R.
AU - Mistry, Pramod
AU - Belmatoug, Nadia
N1 - Funding Information:
We thank the patients, physicians, and staff who submit data to the ICGG Gaucher Registry and the Sanofi Genzyme support team. Sanofi Genzyme employees, Laura Croal, PhD, and Shirali Pandya, PhD, MPH, provided editorial support. Elizabeth Singer, BA, provided programming support. Shelton Panak, PhD, independent medical writer, was funded by Sanofi Genzyme and wrote the first draft of the manuscript and provided editorial support. We also wish to recognize the historic contributions to Gaucher disease research of Professor Emeritus Dr. Robert E. Lee of the Department of Pathology of the University of Pittsburgh, PA, USA. In the 1970s, Dr. Lee created the first Gaucher registry (?The Pittsburgh Registry?) for the clinical study of Gaucher disease phenotypes. He enrolled 535 patients over about 20 years. He was among the first to call attention to macrophage iron storage in GD and to document a then unexpected high prevalence of malignancies in GD patients. Dr. Lee recently passed away at 90 years of age. Sanofi Genzyme., All authors had access to the data, participated in the conceptualization of the research question and interpretation of the analyses, reviewed and edited the manuscript and provided final approval of the manuscript. Authorship was not contingent on the number of patients the author contributed to the data set. Monica R. McClain also conducted the statistical analyses.
Publisher Copyright:
© 2021 The Authors
PY - 2021/2
Y1 - 2021/2
N2 - Background: Alglucerase enzyme replacement therapy was approved for Gaucher disease (GD) in the United States in 1991; imiglucerase in 1994. We report hematologic, visceral, bone pain, bone crisis, height, weight, and Body Mass Index (BMI) outcomes in patients treated for 20 (±3) years with subset analyses based on pre-treatment severity, genotype, and age at treatment initiation. Methods: GD type 1 (GD1) patients in the ICGG Gaucher Registry with complete sets of baseline, 10-year, and 20-year data are included (N = 475). Ten-year and 20-year data are compared to pre-treatment baseline, stratified by splenectomy status. Results: Non-splenectomized patients: Improvements observed at 10 years were maintained at 20 years for most outcomes. Mean changes from baseline at 10 and 20 years, respectively, were: spleen volume: 18.2 multiples of normal (MN) to 5.1 MN and 4.2 MN; liver volume: 1.8 MN to 1.0 MN and 1.0 MN; hemoglobin: 11.4 g/dL to 13.7 g/dL and 13.8 g/dL; platelet count: 91.6 × 109/L to 168.0 × 109/L and 169.1 × 109/L; without bone crisis: 85.0% to 98.2% and 96.5%; without bone pain: 52.5% to 72.0% at 10 years, no significant change at 20 years (58.5%). Splenectomized patients: significant changes were observed in liver volume: 2.3 MN to 1.1 MN and 1.0 MN; hemoglobin: 11.7 g/dL to 13.3 g/dL and 13.4 g/dL; platelet count: 229.1 × 109/L to 288.1 × 109/L and 257.0 × 109/L; without bone crisis: 52.2% to 91.3% and 100%; without bone pain: 16.3% to 30.6% (not significant) and 46.9%. Similar results were found in each of the subset analyses. Patients who start treatment during childhood have normal weight and height in young adulthood. Many treated adult patients are overweight or obese; however, this is consistent with BMI trends observed in the general population. After 1–2 years, the average biweekly imiglucerase dose is ~40 units/kg body weight. Conclusion: Imiglucerase is an effective, long-term treatment for GD1. In a long-term observational setting, improvements seen during early treatment years are sustained by continuing treatment for 20 years, except for bone pain in non-splenectomized patients. These results are consistent when analyzed by different patient subsets, including by disease severity.
AB - Background: Alglucerase enzyme replacement therapy was approved for Gaucher disease (GD) in the United States in 1991; imiglucerase in 1994. We report hematologic, visceral, bone pain, bone crisis, height, weight, and Body Mass Index (BMI) outcomes in patients treated for 20 (±3) years with subset analyses based on pre-treatment severity, genotype, and age at treatment initiation. Methods: GD type 1 (GD1) patients in the ICGG Gaucher Registry with complete sets of baseline, 10-year, and 20-year data are included (N = 475). Ten-year and 20-year data are compared to pre-treatment baseline, stratified by splenectomy status. Results: Non-splenectomized patients: Improvements observed at 10 years were maintained at 20 years for most outcomes. Mean changes from baseline at 10 and 20 years, respectively, were: spleen volume: 18.2 multiples of normal (MN) to 5.1 MN and 4.2 MN; liver volume: 1.8 MN to 1.0 MN and 1.0 MN; hemoglobin: 11.4 g/dL to 13.7 g/dL and 13.8 g/dL; platelet count: 91.6 × 109/L to 168.0 × 109/L and 169.1 × 109/L; without bone crisis: 85.0% to 98.2% and 96.5%; without bone pain: 52.5% to 72.0% at 10 years, no significant change at 20 years (58.5%). Splenectomized patients: significant changes were observed in liver volume: 2.3 MN to 1.1 MN and 1.0 MN; hemoglobin: 11.7 g/dL to 13.3 g/dL and 13.4 g/dL; platelet count: 229.1 × 109/L to 288.1 × 109/L and 257.0 × 109/L; without bone crisis: 52.2% to 91.3% and 100%; without bone pain: 16.3% to 30.6% (not significant) and 46.9%. Similar results were found in each of the subset analyses. Patients who start treatment during childhood have normal weight and height in young adulthood. Many treated adult patients are overweight or obese; however, this is consistent with BMI trends observed in the general population. After 1–2 years, the average biweekly imiglucerase dose is ~40 units/kg body weight. Conclusion: Imiglucerase is an effective, long-term treatment for GD1. In a long-term observational setting, improvements seen during early treatment years are sustained by continuing treatment for 20 years, except for bone pain in non-splenectomized patients. These results are consistent when analyzed by different patient subsets, including by disease severity.
KW - Enzyme replacement therapy
KW - Gaucher disease
KW - Gaucher registry
KW - Imiglucerase
KW - Long-term outcomes
KW - Severity
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U2 - 10.1016/j.ymgme.2020.12.295
DO - 10.1016/j.ymgme.2020.12.295
M3 - Article
C2 - 33485799
AN - SCOPUS:85099612213
VL - 132
SP - 100
EP - 111
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 2
ER -
