Imiglucerase (Cerezyme((R))) improves quality of life in patients with skeletal manifestations of Gaucher disease

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Clinical Genetics (Impact Factor: 3.93). 07/2007; 71(6):576-88. DOI: 10.1111/j.1399-0004.2007.00811.x
Source: PubMed


Health-related quality of life (HRQOL) can be diminished in patients with type 1 Gaucher disease (GD) owing to the debilitating clinical manifestations of this chronic disease. This study investigates the impact of imiglucerase treatment on HRQOL of patients with type 1 GD and bone involvement. Thirty-two previously untreated type 1 GD patients with skeletal manifestations including bone pain, medullary infarctions, avascular necrosis, and lytic lesions received biweekly imiglucerase (at 60 U/kg). The Short Form-36 Health Survey (SF-36) was administered at regular intervals to assess HRQOL. Mean baseline SF-36 physical component summary (PCS) scores were diminished relative to US general population norms. Low PCS scores were more common in patients with medullary infarction, lytic lesions, and higher bone pain severity scores. Statistically significant improvements were observed for all eight SF-36 subscales after 2 years of treatment. Mean PCS and mental component summary (MCS) scores increased to within the normal range after 2 years of treatment and were maintained through year 4. Large HRQOL gains were observed even in patients with the most advanced disease and lowest baseline PCS scores. Imiglucerase treatment has a significant positive impact on HRQOL of type 1 GD patients with skeletal disease, including those with bone infarctions, lytic lesions, and avascular necrosis.

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    • "study are consistent with Kuratsubo's (2009) suggestion with MPS II subjects that when cognitive abilities are preserved, subjects may display increased psychological symptoms as a result of understanding their disease burden more fully. Research in other LSDs, such as Fabry disease (FD) and Gaucher disease (GD), has likewise documented decreased QOL and begun to examine psychological functioning (Crosbie et al. 2009; Gold et al. 2002; Masek et al. 1999; Packman et al. 2006; Watt et al. 2010; Weinreb et al. 2007; Wilcox et al. 2008). Prevalence estimates of depression in FD range from 15 to 62% (Bolsover et al. 2014; Grewal 1993; Wang et al. 2007), with the largest study (n ¼ 296) reporting 46% (Cole et al. 2007). "

    Full-text · Article · Feb 2015 · Molecular Genetics and Metabolism
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    • "le , save for a relatively small number of patients with pretreatment complications , such as fibrotic spleen or liver fibrosis and portal hypertension . On the other hand , skeletal manifestations associated with untreated GD1 have the poten - tial to cause long - term disability and negatively impact the patient ' s quality of life permanently ( Weinreb et al . 2007 ) . In this study , by the time treatment was begun , bone pain was reported by the majority of nonsplenectomized ( 98 / 187 ) and nearly all splenectomized ( 48 / 54 ) patients . Bone crises , which often signal irreversible osteonecrosis , were reported not only in splenectomized ( 18 / 47 ) patients , but also in those with intact sp"
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    ABSTRACT: Objective: We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). Methods: The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within-patient absolute change in continuous measurements and McNemar/chi-square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance. Results: As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks. Conclusion: Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.
    Full-text · Article · Sep 2012 · Journal of Inherited Metabolic Disease
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    • "The infiltration of bone marrow by Gaucher cells imparts a clear signature on magnetic resonance imaging of the skeleton as the normal fat signal in adult marrow is replaced by a more hydrated cellular infiltrate.72 Bone mineralization density is often reduced and salutary responses to treatment are readily documented by conventional dual energy X-ray absorptiometry.72–76 Subjective measures are also revealing; validated clinical scores of pain, fatigue, and health-related quality of life are sensitive to the evolution and amelioration of disease.77–79 "
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    ABSTRACT: The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease.
    Full-text · Article · Apr 2012 · Drug Design, Development and Therapy
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