title: Miglustat therapy in type 1 Gaucher disease: clinical and safety outcomes in a multicenter retrospective cohort study.
abstract: We evaluated clinical and safety outcomes in adult patients with type 1 Gaucher disease receiving miglustat in clinical practice settings. An observational, retrospective cohort study was conducted in centers across the EU and the USA. Medical chart data were collected from consecutive patients between the 20th November 2002 and 31st December 2008. A total of 115 patients were included; 34 (30%) were enzyme replacement therapy-naïve ('naïve') and 81 (70%) were enzyme pretreated ('pretreated'). Median (range) miglustat exposures in these groups were 15.1 (0.6-52.9)months and 15.2 (0.3-62.1)months, respectively. Low numbers of patients were anemic (10/101) or thrombocytopenic (21/101) at initiation of miglustat therapy. The median (range) hemoglobin concentration at miglustat initiation was 12.8 (10.2-16.4)g/dl in naïve patients and 13.6 (7.3-17.4)g/dl in pretreated patients; median (range) changes in hemoglobin were 0.3 (-2.5-3.6) and -0.3 (-4-4.6)g/dl, respectively. The median (range) platelet counts at miglustat initiation were 101 (37-730)×10(9)/l in naïve patients and 173 (43-382)×10(9)/l in pretreated patients; median (range) changes in platelet count were 8 (-77-145)×10(9)/l and -10 (-144-434)×10(9)/l, respectively. Plasma chitotriosidase was substantially reduced in naïve but not in pretreated patients. Organ volumes were not routinely monitored. Forty-nine (43%) patients discontinued miglustat; most due to gastrointestinal manifestations and some due to tremor. Overall, hemoglobin and platelet counts tended to increase in naïve patients treated with miglustat, and to remain stable or decrease slightly in pretreated patients. The profile of safety and tolerability observed with miglustat in the current study is similar to previous studies.
authors.affiliation: Hematology Division, Massachusetts General Hospital, Boston, MA 02114, USA. DKUTER@PARTNERS.ORG
authors.forename: David J
authors.initials: DJ
authors.lastname: Kuter
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.forename: Monika
authors.initials: M
authors.lastname: Brand
authors.forename: Audrey
authors.initials: A
authors.lastname: Muller
authors.forename: Berthold
authors.initials: B
authors.lastname: Schaaf
authors.forename: Ruben
authors.initials: R
authors.lastname: Giorgino
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D065089:Glycoside Hydrolase Inhibitors; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D006454:Hemoglobins; D017485:1-Deoxynojirimycin; C059896:miglustat