What is enzyme replacement therapy for Gaucher disease?
The clinical effectiveness of enzyme replacement therapy for patients with Gaucher disease was first investigated in the 1990s.1 This concept originated in 1966, when a marked reduction in glucocerebrosidase enzyme activity was reported in the spleen of patients with Gaucher disease.2 Enzyme replacement therapy is indicated for various signs and symptoms of Gaucher disease, including anaemia, thrombocytopaenia, bone disease, hepatomegaly and splenomegaly.3 The principle of enzyme replacement therapy is to supply cells, particularly Gaucher cells, with the necessary glucocerebrosidase enzyme activity (Figure 1).4
The first enzyme replacement therapy was placenta-derived alglucerase in 1991, which was replaced by human recombinant Chinese hamster ovary (CHO)-cell–derived imiglucerase in 1995. In 2010 and 2012, two newly developed enzyme replacement therapies became available: velaglucerase alfa, which is produced by gene activation technology in a human fibroblast cell line, and the plant-cell–derived human recombinant protein taliglucerase alfa, respectively.3,5
The availability of these treatments differs between countries. For further information, please consult your local prescribing information.
Enzyme replacement therapy restores the breakdown of glucosylceramide in patients with Gaucher disease
What studies have been performed looking at patients' attitudes toward enzyme replacement therapy?
Patient survey studies have been conducted in various geographies regarding use of both enzyme replacement therapies and substrate reduction therapies. Patient attitudes toward substrate reduction therapies can be accessed here.
In a study of health-related quality of life in 212 patients aged ≥14 years (mean [standard deviation] age, 45  years) with Gaucher disease (recruited by 146 physicians in the US), patients had been receiving enzyme replacement therapy for 1‒51 months at the time of study enrollment. Patients reported improvements in physical, general and emotional well-being following initiation of treatment, as follows6:
- 53% had fewer limitations in physical activities
- 77% had improvements in general health perceptions
- 49% experienced reduced negative emotions.
It was also found that longer duration of therapy was significantly associated with better mental health (p<0.01).6
A qualitative study, conducted in Australia, of young patients with lysosomal storage diseases (including Gaucher disease, mucopolysaccharidosis types I or II, or Pompe disease) and their families (7 families; 15 interviews) aimed to explore the impact that enzyme replacement therapy had on quality of life. All patients were either primary school age or teenagers. In total, nine parents, four patients receiving enzyme replacement therapy, and three siblings were interviewed. Results from this study suggested that participants had a positive attitude towards enzyme replacement therapy, and they felt that it improved their own health and health-related quality of life, as well as that of their children or their siblings. It was reported that the time commitments and visits to specialised centres associated with intravenous infusions of enzyme replacement therapy could affect lifestyle choices, and participants expressed their interest in home-based infusions which could allow more flexibility in how they accessed treatment.7
In a UK questionnaire-based satisfaction survey of 25 patients with Gaucher disease who were receiving enzyme replacement therapy, 84% indicated that they preferred home-based enzyme replacement therapy as, in their opinion, it was more comfortable, less stressful, and had less impact on family life compared with hospital-based treatment.8 Similarly, in a separate study of 42 patients with lysosomal storage diseases (including Fabry disease, Gaucher disease, mucopolysaccharidosis types I, II or IV, or Pompe disease) who were receiving hospital-based enzyme replacement therapy in Italy, 93% felt that this made them feel safer. These patients also reported that they felt hospital-based enzyme replacement therapy allowed closer monitoring and more support from healthcare professionals, compared with home-based infusions.9
Physicians should therefore take an individualised approach to treatment, accounting for their patients’ needs, and, when possible, should include patients in the decision-making process when discussing treatment options.7
Data from these studies should be interpreted with caution, in light of the period these studies were conducted and the study locations. The availability of these treatments differs between countries. For further information, please consult your local prescribing information. Moreover, introduction to the market of each treatment differs for enzyme replacement therapies (imiglucerase, 1995; velaglucerase alfa, 2010; taliglucerase alfa, 2012) and substrate reduction therapies (miglustat, 2002; eliglustat, 2014),3 which may have influenced patient attitudes towards treatment depending upon when the study was performed.
C-ANPROM/INT//7568; Date of preparation:September 2020
- Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 1991; 324: 1464-1470.
- Brady RO, Kanfer JN, Bradley RM, et al. Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease. J Clin Invest 1966; 45: 1112-1115.
- Revel-Vilk S, Szer J, Mehta A, et al. How we manage Gaucher disease in the era of choices. Br J Haematol 2018; 182: 467-480.
- Stirnemann J, Belmatoug N, Camou F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci 2017; 18: 441.
- Shire Pharmaceuticals Ltd. VPRIV® EU Summary of Product Characteristics. Last updated August 2020.
- Damiano AM, Pastores GM, Ware JE, Jr. The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study. Qual Life Res 1998; 7: 373-386.
- Freedman R, Sahhar M, Curnow L, et al. Receiving enzyme replacement therapy for a lysosomal storage disorder: a preliminary exploration of the experiences of young patients and their families. J Genet Couns 2013; 22: 517-532.
- Milligan A, Hughes D, Goodwin S, et al. Intravenous enzyme replacement therapy: better in home or hospital? Br J Nurs 2006; 15: 330-333.
- Parini R, Pozzi K, Di Mauro S, et al. Intravenous enzyme replacement therapy: hospital vs home. Br J Nurs 2010; 19: 892-894, 896-898.
- Sanofi Genzyme. Cerezyme® EU Summary of Product Characteristics. Last updated March 2020.
- Pfizer Canada Inc. ELELYSO® Product Monograph. Last updated August 2017.