Low frequency maintenance therapy with imiglucerase in adult type I Gaucher disease: a prospective randomized controlled trial

• Published in: Haematologica (Roma) 2007-02, Vol.92 (2), p.215-221
• Main Authors: de Fost, Maaike, Aerts, Johannes M.F.G, Groener, Johanna E.M, Maas, Mario, Akkerman, Erik M, Wiersma, Maaike G, Hollak, Carla E.M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anemia - drug therapy; Anemias. Hemoglobinopathies; Biological and medical sciences; Diseases of red blood cells; Errors of metabolism; Female; Ferritins - blood; Gaucher Disease - drug therapy; Glucosylceramidase - administration & dosage; Glucosylceramidase - therapeutic use; Hematologic and hematopoietic diseases; Hexosaminidases - blood; Humans; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Mutation; Peptidyl-Dipeptidase A - blood; Prospective Studies; Thrombocytopenia - drug therapy; Treatment Outcome
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.10635

From the Department of Endocrinology and Metabolism (MdF, MGW, CEMH); Medical Biochemistry (JMFGA, JEMG); Radiology (MM, EMA), Academic Medical Centre, Amsterdam, the Netherlands Correspondence: Carla E.M. Hollak, Department of Endocrinology and Metabolism, F4-279, University of Amsterdam, Academic Medical Center P.O. Box 22700, 1100 DD Amsterdam, the Netherlands. E-mail: c.e.hollak{at}amc.uva.nl Background and Objectives: Gaucher disease type I can be successfully treated with enzyme replacement therapy (ERT). In order to reduce the burden of the intravenously administered enzyme, a low frequency of administration was prospectively studied in patients with stable and minor disease following ERT. Design and Methods: Eleven patients were randomly assigned either to continue their original regimen of a dose of ERT once every week or fortnight (five patients) or to lower the frequency of administration to once every 4 weeks, at the same cumulative dose (six patients). The primary end-point was change in liver ratio (mL/kg body weight). Secondary end-points were spleen volume, hemoglobin level, platelet count, lumbar bone marrow fat content measured with quantitative chemical shift imaging (QCSI), white cell count, and plasma levels of ferritin, chitotriosidase, liver enzymes and angiotensin-converting enzyme (ACE). Results: There were no significant mean differences between the two treatment arms in liver ratio or any of the other end-points. However, there were two treatment failures in the low frequency of administration group. These patients showed progression of disease as evidenced by a reduction of QCSI in one patient and an increase in liver ratio as well as a slow decrease in QCSI in the other. Both patients already had relatively low baseline QCSI values. One patient switched back to the original regimen at 6 months because of subjective complaints. Interpretation and Conclusions: Low frequency ERT in adult Gaucher type I patients maintains stable disease in most, but not all patients with stable and minimal disease. Close monitoring of all disease parameters remains mandatory. Key words: Gaucher disease, anemia, thrombocytopenia, randomized trial. Related Article Therapy of adult Gaucher disease Joerg Schmitz, Ludger Wilhelm Poll, Stephan vom Dahl Haematologica 2007 92: 148-152. [Full Text] [PDF]