Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment

for the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigators

doi:10.1016/j.ymgme.2020.12.295

Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment

for the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigators

Pediatrics

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	100-111
Number of pages	12
Journal	Molecular Genetics and Metabolism
Volume	132
Issue number	2
DOIs	https://doi.org/10.1016/j.ymgme.2020.12.295
State	Published - Feb 2021

Funding

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. 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.

Keywords

Enzyme replacement therapy
Gaucher disease
Gaucher registry
Imiglucerase
Long-term outcomes
Severity

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

Access to Document

10.1016/j.ymgme.2020.12.295

Cite this

@article{742c68a0eff347e8a2fae414b0533854,

title = "Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment",

abstract = "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.",

keywords = "Enzyme replacement therapy, Gaucher disease, Gaucher registry, Imiglucerase, Long-term outcomes, Severity",

author = "{for the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigators} and Weinreb, {Neal J.} and Camelo, {Jos{\'e} Simon} and Joel Charrow and McClain, {Monica R.} and Pramod Mistry and Nadia Belmatoug",

note = "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. 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. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = feb,

doi = "10.1016/j.ymgme.2020.12.295",

language = "English (US)",

volume = "132",

pages = "100--111",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "2",

}

Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment. / for the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) investigators.
In: Molecular Genetics and Metabolism, Vol. 132, No. 2, 02.2021, p. 100-111.

Research output: Contribution to journal › Article › peer-review

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. 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. 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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ER -

Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment

Abstract

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ASJC Scopus subject areas

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