Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis.
Dosing of enzyme replacement therapy (ERT) for Gaucher disease type 1 is still a subject of debate and varies from 15 to 130 U/kg/mo, making a huge economic difference of 70,000 US dollars to 380,000 US dollars(euro55,000-300,000) per patient per year. To investigate whether this difference in dosing ultimately translates into a different response, we retrospectively compared long-term outcome of ERT at 2 large European treatment centers, Academic Medical Center, Amsterdam, The Netherlands (n = 49, median dose, 15-30 U/kg/4 wks) and Heinrich-Heine University, Duesseldorf, Germany (n = 57, median dose, 80 U/kg/4 wks). These adult cohorts had a similar genetic background. All follow-up parameters were matched separately at baseline, to avoid bias with respect to disease severity. Improvement in hemoglobin, platelet count, and hepatosplenomegaly was not significantly different between both cohorts, whereas plasma chitotriosidase and bone marrow involvement by magnetic resonance imaging improved more quickly and was more pronounced in the higher-dosed group. Major bone complications rarely occurred in both groups. In conclusion, different dosing regimens of ERT do not affect outcome of hematologic and visceral parameters, but higher dosing leads to accelerated decrease of chitotriosidase and better objective bone response in adult type 1 Gaucher disease.
de Fost
Maaike
M
Department of Internal Medicine, Endocrinology and Metabolism, F4-279, University of Amsterdam, Academic Medical Center, 1100 DD Amsterdam, The Netherlands.
Hollak
Carla E M
CE
Groener
Johanna E M
JE
Aerts
Johannes M F G
JM
Maas
Mario
M
Poll
Ludger W
LW
Wiersma
Maaike G
MG
Häussinger
Dieter
D
Brett
Sarah
S
Brill
Nicole
N
vom Dahl
Stephan
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000209:etiology / Q000517:prevention & control; D001853:Bone Marrow / Q000473:pathology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000008:administration & dosage* / Q000191:economics / Q000494:pharmacology; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000188:drug therapy*; D006454:Hemoglobins; D006596:Hexosaminidases / Q000097:blood* / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012189:Retrospective Studies; D013163:Splenomegaly / Q000209:etiology / Q000517:prevention & control
D004798:Enzymes; D006454:Hemoglobins; D006596:Hexosaminidases; C086400:chitotriosidase