Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment

Abstract

Objective: We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1).

Methods: The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within-patient absolute change in continuous measurements and McNemar/chi-square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance.

Results: As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks.

Conclusion: Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.

Conflict of interest statement

Neal Weinreb receives honoraria and expense reimbursement for serving on a Board of Advisors of the ICGG Gaucher Registry; and travel reimbursements and/or honoraria and/or research support from Genzyme, Shire Pharmaceuticals, Amicus Therapeutics, Protalix Corporation, and Actelion. He has been a study safety board advisor for Synageva Corporation. Jack Goldblatt has received reimbursements and/or honoraria from Genzyme, Shire Pharmaceuticals, Pfizer, Protalix and Actelion. Joel Charrow receives honoraria and expense reimbursement for serving on a Board of Advisors of the ICGG Gaucher Registry and the Fabry Registry and has received consulting fees from Shire Pharmaceuticals and Protalix. Carla Hollak has received honoraria and expense reimbursement for serving on a Board of Advisors of the European ICGG Gaucher Registry, and honoraria and expense reimbursement for lectures from Genzyme, Actelion and Shire Pharmaceuticals. Dr. Hollak donates all honoraria to Gaucher Stichting, a national foundation that supports research in the field of lysosomal storage disorders. Stephan vom Dahl has received honoraria and expense reimbursement for serving on a Board of Advisors of the European ICGG Gaucher Registry, fees for speaking from Genzyme, Shire, Protalix and Actelion and consulting for Actelion. Marcelo Kerstenetzky has received fees for consulting from Genzyme and Biomarin. Jacobo Villalobos has received fees for speaking from Genzyme. J. Alexander Cole is an employee of Genzyme.