title: Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier NCT00319046.
authors.affiliation: University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. tmc12@medschl.cam.ac.uk
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Cox
authors.forename: Dominick
authors.initials: D
authors.lastname: Amato
authors.forename: Carla Em
authors.initials: CE
authors.lastname: Hollak
authors.forename: Cecile
authors.initials: C
authors.lastname: Luzy
authors.forename: Mariabeth
authors.initials: M
authors.lastname: Silkey
authors.forename: Ruben
authors.initials: R
authors.lastname: Giorgino
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D057487:Enzyme Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat