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 (CerezymeTM) 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.