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 TM ) 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.

Characteristics of 27 patients with type 3 Gaucher disease: a descriptive analysis from the Gaucher Outcome Survey

“…In this analysis, 3 of 33 (9.1%) patients enrolled in GOS in Brazil had GD3, compared with a previous report of 5% [29], although absolute numbers were small. Given the low patient numbers involved, the percentage of patients reported as having GD3 in GOS (2.7%) is similar to that reported by other registry studies (5%), which typically include countries known to have higher prevalence rates of GD3, such as Sweden, Egypt, China, India, Korea, and Japan [4][5][6][7][8][9]. Further work would be needed to establish whether the GBA1 genotype, disease course, and clinical characteristics of patients with GD3 in GOS differ from those in countries with a higher prevalence of GD3.…”

“…Patients with type 2 (acute neuronopathic) GD (GD2) suffer rapid deterioration, with death usually occurring before 2 years of age, while patients with type 3 (chronic neuronopathic) GD (GD3) experience a slower disease course [3]. An estimated 5% of patients with GD in Europe, North America, and Israel are affected by type 3 disease [3,4], but much higher percentages have been reported in some countries, including Sweden, Egypt, China, India, Korea, and Japan [4][5][6][7][8][9].…”

Zarys objawów klinicznych, leczenia oraz trudności w rozpoznawaniu choroby Gauchera

“…Pewne obszary geograficzne oraz grupy ludności są bardziej dotknięte występowaniem choroby Gauchera niż pozostałe [27]. Na przykład na północy Szwecji, nad Zatoką Botnicką, w rejonach Norrbotten i Västerbotten, częstość występowania choroby Gauchera jest większa i wynosi ok. 1:10 000 mieszkańców [16,17].…”

“…3), zwykle przed 2 rokiem życia, choć może się czasem objawiać u nastolatków [16,17]. W typie 3 choroby Gauchera (GD3), poza objawami hematologicznymi, trzewnymi i kostnymi, takimi jak w GD1, występuje także zajęcie OUN przez proces neurodegeneracyjny [3,27]. Początkowo zajęcie OUN przejawia się w postaci nieprawidłowych ruchów gałek ocznych (sakad poziomych), ale z czasem dochodzi do nasilenia objawów neurologicznych: paraparezy spastycznej, ataksji, padaczki mioklonicznej, utraty koordynacji mięśniowej, trudności w uczeniu się oraz wolno postę-pującej demencji [16,17].…”

Atypical cytomorphology of Gaucher cells is frequently seen in bone marrow smears from untreated patients with Gaucher disease type 1

“…Three clinical types of GD are distinguished according to the absence (type 1) or presence (types 2 and 3) of neurological symptoms and the dynamics of developing clinical signs [1,2,12]. The most prevalent form of GD is non-neuronopathic GD type 1 (GD1).…”