title: Miglustat (Zavesca) in type 1 Gaucher disease: 5-year results of a post-authorisation safety surveillance programme.
abstract: OBJECTIVE
  Miglustat (Zavesca) is an orally-available substrate reduction therapy (SRT) for treatment of mild-to-moderate type 1 Gaucher disease (GD1) in adult patients unsuitable for enzyme replacement therapy (ERT). Miglustat has not been evaluated in children with GD1, and is not used during pregnancy and breast-feeding. A non-interventional, prospective, web-based safety surveillance programme was initiated at the time of the European launch of miglustat in 2003, and is ongoing. We report the first 5 years of collected data, focusing on neurological manifestations.
  
  
  METHODS
  Data were collected on 122 GD1 patients between March 2003 and April 2008, representing 244 patient-years cumulative miglustat post-authorisation experience. The electronically-captured data collected from participating physicians includes patient demographics, prior and current therapies, baseline disease manifestations and concurrent conditions, disease severity, duration of miglustat exposure, and safety-relevant information.
  
  
  RESULTS
  Mean (SD) age at baseline was 46.1 (16.5) years. At baseline, bone disease and neurological manifestations were reported in 55.6 and 28.6% of patients, respectively; the latter included peripheral neuropathy (7.2%) and a wide variety of neurological symptoms and signs. In addition, 23.2% had other health conditions relevant to neurological status. During the reporting period, new neurological manifestations were reported in 23 (18.9%) patients, principally tremor. Thirty-five (28.7%) patients discontinued treatment, predominantly for gastrointestinal (GI) disturbances (11.5%), two-thirds of which occurred during the first 6 months.
  
  
  CONCLUSIONS
  The safety profile of miglustat in GD1 patients included in the safety surveillance programme is overall consistent with that reported in the registration and other clinical trials, and no new safety finding was identified.
authors.affiliation: Academic Medical Center, 1100 DE Amsterdam, The Netherlands. c.e.hollak@amc.uva.nl
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.forename: Ivo N
authors.initials: IN
authors.lastname: van Schaik
authors.forename: Barbara
authors.initials: B
authors.lastname: Schwierin
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000592:standards / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat