title: Impact of imiglucerase supply shortage on clinical and laboratory parameters in Norrbottnian patients with Gaucher disease type 3.
abstract: A viral contamination of the production plant producing imiglucerase (Cerezyme™) resulted in an unpredicted worldwide shortage of global supplies during 2009-2010. The aim of the study was to describe the effects of dose reduction of enzyme replacement therapy (ERT) in adults with Norrbottnian form of Gaucher disease type 3 (N-GD3). There were ten adults with N-GD3 treated with imiglucerase in the county of Norrbotten in June 2009. Analyzed variables included plasma chitotriosidase activity and concentration of CCL18/PARC, whole blood hemoglobin concentration (Hb) and platelet count (PLT), as well as patients' body weight, subjective complaints and health status measured by the EuroQoL-5D questionnaire. The median duration of ERT shortage lasted for 14 months (10-20 months). The median percentage reduction of imiglucerase dose was 36 % (26-59 %). Hb decreased in four patients, PLT decreased in three patients, chitotriosidase increased in three patients (max. +22 % of baseline), and CCL18/PARC increased in six patients (+14 % to +57 %). The body weight was moderately decreased in one patient. No new bone events were noted. Self-assessment of individual patient's health status was stable in all but one patient. Our results suggest that moderate reduction of ERT dosage lasting for relatively short period of time can lead to worsening in biomarkers of adults with N-GD3. However, this worsening is infrequently translated to clinical worsening of patients. It is possible that CCL18/PARC has a higher sensitivity than chitotriosidase in monitoring of ERT dosing in GD3.
authors.affiliation: Medical Faculty, University of Rzeszow, 35-959, Rzeszow, Poland, maciej.machaczka@ki.se.
authors.forename: Maciej
authors.initials: M
authors.lastname: Machaczka
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kämpe Björkvall
authors.forename: Joanna
authors.initials: J
authors.lastname: Wieremiejczyk
authors.forename: Martin
authors.initials: M
authors.lastname: Paucar Arce
authors.forename: Kristina
authors.initials: K
authors.lastname: Myhr-Eriksson
authors.forename: Monika
authors.initials: M
authors.lastname: Klimkowska
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000328:Adult; D001835:Body Weight; D019742:Chemokines, CC / Q000378:metabolism; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000600:supply & distribution* / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011795:Surveys and Questionnaires; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D006454:Hemoglobins; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase; C090568:imiglucerase