Abstract
BackgroundPrevious studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy.MethodsAdult type 1 Gaucher disease patients stabilized during at least 3 years of previous enzyme therapy were included in this 2-year, prospective, open-label non-inferiority study. The primary endpoint was percent change from baseline in liver volume. Secondary endpoints included changes in spleen volume, hemoglobin concentration and platelet count.ResultsForty-two patients were enrolled (mean±SD age, 45.1±12.7 years; previous enzyme therapy duration 9.5±4.0 years). Median (range) exposure to miglustat 100 mg t.i.d. was 658 (3–765) days. Twenty-one patients discontinued treatment prematurely; 13 due to adverse events, principally gastrointestinal. The upper 95% confidence limit of mean percent change in liver volume from baseline to end of treatment was below the non-inferiority margin of 10% (–1.1%; 95%CI −6.0, 3.9%). Mean (95%CI) changes in spleen volume, hemoglobin concentration and platelet count were 102 (24,180) mL, –0.95 (−1.38, –0.53) g/dL and −44.1 (–57.6, –30.7) ×109/L, respectively.ConclusionsThe primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy. Several patients showed a gradual deterioration in some disease manifestations, suggesting that miglustat could maintain clinical stability, but not in all patients. Miglustat demonstrated a predictable profile of safety and tolerability that was consistent with that reported in previous clinical trials and experience in clinical practice.Trial registrationClinicaltrials.gov identifier NCT00319046
Highlights
Type 1 Gaucher disease is an inherited lysosomal disorder caused by impaired activity of β-glucocerebrosidase, and xaccumulation of glucosylceramide in pathologic macrophages in the liver, spleen, bone marrow and, less frequently, the lungs [1,2]
Liver volume was maintained in patients with stable type 1 Gaucher disease who changed to miglustat after previous long-term enzyme therapy
The primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy
Summary
Type 1 Gaucher disease is an inherited lysosomal disorder caused by impaired activity of β-glucocerebrosidase, and xaccumulation of glucosylceramide in pathologic macrophages in the liver, spleen, bone marrow and, less frequently, the lungs [1,2]. Miglustat was approved in Europe in 2002 and in the USA in 2003 for use as a substrate reduction therapy in adult patients with mild-to-moderate type 1 Gaucher disease for whom enzyme therapy is unsuitable or not a therapeutic option [10,11]. Previous studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy
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