Abstract
J Inherit Metab Dis 2013;
The lysosomal storage disorder (LSD) Gaucher disease (GD) results from loss of function of the enzyme glucocerebrosidase, leading to accumulation of glucocerebroside. Clinical manifestations of GD include anaemia, thrombocytopaenia, splenic and hepatic enlargement, and skeletal disease.
GD1 was the first LSD to be treated with enzyme replacement therapy. From 1991, imiglucerase (Genzyme, Cambridge, MA, USA) has been used to effectively treat the clinical manifestations of GD. Evaluation of haematological, organ response and skeletal manifestation is the minimum criteria for evaluating treatment efficacy.
This study analysed the response of GD1 (non-neuronopathic) patients at first infusion and after 10 years of imiglucerase therapy to assess whether response was maintained.
GD1 patients were identified from the International Collaborative Gaucher Group Registry. Only GD1 patients with dose and clinical data at first imiglucerase infusion and after 10 years were included. Subsets were created by data for haemoglobin, platelet count, liver and spleen volume, bone pain and crisis. Data were further analysed by splenectomy status as this intervention is known to have an immediate and persistent effect on GD pathophysiology.
Seven hundred and fifty seven GD patients met the study criteria, with 200 being splenectomized. Results indicated that all parameters improved significantly (P < 0.05) after 10 years of imiglucerase treatment. Most (90%) patients anaemic at first infusion had normalized haemoglobin at 10 years and the number of patients with severe thrombocytopaenia decreased significantly (P < 0.0001). Hepatic volume and incidence of bone pain and crisis also decreased significantly (P < 0.05) in all patients.
Limitations of this study included small numbers for some parameters, as organ imaging is rare after long-term treatment. The use of two fixed time points may not accurately reflect chronic state and reported bone pain may not be entirely attributable to GD.
In conclusion, 10 years of imiglucerase therapy results in sustainable improvements in all GD1 parameters.