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Open Access Research

Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study

Timothy M Cox1*, Dominick Amato2, Carla EM Hollak3, Cecile Luzy4, Mariabeth Silkey4, Ruben Giorgino4, Robert D Steiner5 and for the Miglustat Maintenance Study Group

Author Affiliations

1 University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

2 Mount Sinai Hospital, University of Toronto, Toronto, Canada

3 Academic Medical Centre, Amsterdam, The Netherlands

4 Actelion Pharmaceuticals Ltd, Allschwil, Switzerland

5 Child Development and Rehabilitation Center/Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, OR, USA

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Orphanet Journal of Rare Diseases 2012, 7:102  doi:10.1186/1750-1172-7-102

Published: 27 December 2012



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.


Adult 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.


Forty-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.


The 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 registration identifier NCT00319046

Gaucher disease; Miglustat; Enzyme therapy; Maintenance; Efficacy; Safety