Long-Term Data From the ICGG Gaucher Registry: Clinical Parameters After 10 Years of Treatment with Imiglucerase.
Authors: Weinreb Neal J. , vom Dahl Stephan , Cappellini Maria Domenica 
Published: October 2019

Abstract
Abstract 3590
Poster Board III-527
Introduction Gaucher disease (GD) results from an inherited deficiency of acid β-glucosidase leading to accumulation of glucosylceramide in tissue macrophages, causing hematologic, visceral organ, and skeletal abnormalities. The International Collaborative Gaucher Group (ICGG) Gaucher Registry, begun in 1991, is the largest existing source of information on GD natural history and the effect of disease-specific treatment. Enzyme replacement has been available in the US since 1991 (alglucerase; imiglucerase since 1994).

Objective
To provide updated information regarding GD and the treatment effect of imiglucerase based on data from the ICGG Gaucher Registry.

Methods
Observational data from all patients enrolled in the ICGG Gaucher Registry as of December 31, 2008 were analyzed. All patients listed as “treated” have received enzyme replacement with alglucerase or imiglucerase, but may not currently be receiving treatment. Descriptive statistics were used to characterize demographics and clinical manifestations. Follow-up for treated patients continued for up to 10 years following initiation of treatment.

Results
As of December 31, 2008, 5,323 GD patients were enrolled. The majority of patients (74%) were diagnosed with GD before age 30 (mean age, 19y). 81% of genotyped patients had at least one copy of the N370S mutation. At diagnosis, anemia was reported in 34% of patients and platelet count <120,000/μL in 59%. Splenomegaly (>5 multiples of normal, MN) was reported in 85% of patients and hepatomegaly (liver volume >1.25 MN) in 63%. Bone pain was reported in 34% of patients and radiologic bone disease was reported in 82%. 79% of patients had been treated with alglucerase/imiglucerase. Clinical status after 10 years of treatment was available for up to 758 patients with GD type 1. Mean hemoglobin concentrations improved and mean platelet counts rose to the normal range after 1 year and stayed steady through year 10. Spleen enlargement decreased from a mean of 16.7MN around the time treatment was initiated to 10.5MN after 1 year and further decreased to a mean of 5.4MN at year 10 (n=174). Mean liver volume was 1.8MN around the time treatment was initiated, reached near-normal levels by year 3 (1.2MN; n=746), and was normal at year 10 (n=240). Most treated patients met 6 key therapeutic goals (as defined in Pastores et al., Semin Hematol 2004; 41 [4 Suppl 5]: 4-14) as of their most recent assessment; proportions of patients at each goal were: hemoglobin levels 91%, platelet count 80%, liver volume 85%, spleen volume 69%, bone crisis 96%, and bone pain 65%.

Conclusions
These long-term data show that enzyme replacement with imiglucerase as used in actual clinical practice leads to demonstrable improvements in the major hematologic and visceral manifestations of GD type 1. Robust data regarding the effectiveness of Gaucher disease therapies is particularly useful with expected arrival of new enzyme products soon; the Gaucher Registry, with its large patient base and ability to track long-term data, is a valuable tool for assessing the effects of treatment as they are applied in actual clinical practice.

Disclosures:
Weinreb: Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. vom Dahl:Genzyme Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cappellini:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees.