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Alglucerase

A Pharmacoeconomic Appraisal of its Use in the Treatment of Gaucher’s Disease

  • Alglucerase: A Pharmacoeconomic Appraisal
  • Ceftazidime or Combination Therapy for Febrile Neutropenia
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Summary

Synopsis

Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher s disease, in whom functional glucocerebrosidase is deficient. Alglucerase has provided a breakthrough in treatment for patients with this relatively rare disease. With alglucerase infusions typical disease manifestations are ameliorated or normalised: hepatosplenomegaly is reduced, haematological parameters improve, and patients experience an increased quality of life usually within 4 to 6 months of treatment. Parameters of bone disease also respond, but generally over a longer period of treatment. Alglucerase is well tolerated by children and adults, with few adverse effects reported. Seroconversion occurs in approximately 15% of patients on high—dose therapy, but does not appear to affect the efficacy of treatment.

Several dosage regimens have been used to deliver alglucerase, and the comparative benefits of these remain controversial. High-dose regimens of 60 IU/kg bodyweight administered every 2 weeks are clearly effective; however, smaller dosages given more frequently are also effective and incur a greatly reduced acquisition cost. Patient responses are variable, and the dosage regimen should be tailored to individual needs. Dosage regimens may be considerably reduced for the maintenance phase of treatment, but clinical experience is as yet insufficient to establish the minimum dosages required in the long term.

Acquisition cost of alglucerase is $US3.70 per unit (1994 US dollars); thus, a dosage regimen of60 IU/kg bodyweight administered every 2 weeks for a patient weighing 70kg costs $US404 040 per year. The minimal costs per quality-adjusted life year saved (QALY) have been estimated for 3 dosage regimens over a 10-year periodo Cost per QALY was $US147 000 for 60 IU/kg bodyweight administered every 2 weeks, $US75 000 for 30 IU/kg every 2 weeks, and $US49 000 for 2.3 IU/kg administered 3 times per week. These costs were calculated assuming immediate death with no treatment, which suggests that the actual costs per QALY for most patients with type 1 or 3 disease are likely to be much higher. Drug administration costs may become a significant part of the cost during maintenance therapy; in addition, possible cost savings due to increased patient productivity and reduced palliative treatments remain unresolved.

Although some patients may obtain increased benefit from high-dosage regimens, the very high cost may preclude general use of these regimens. Healthcare resources consumed by alglucerase therapy represent a large opportunity cost for other therapeutic areas. Savings in treatment costs may be achieved by frequent administration of smaller doses in a home environment (to decrease administration costs). Further research to develop less expensive means of manufacturing the enzyme is urgently required, as current acquisition costs may limit treatment to only the most severely affected patients.

In conclusion, enzyme replacement therapy is the most effective and well tolerated treatment available for Gaucher’s disease. However, the cost effectiveness of this expensive treatment has not yet been established.

Disease Considerations

Gaucher’s disease resu1ts from an inherited inability to hydrolyse glucocerebroside, a byproduct of cell membrane metabolismo Excessive storage of glucocerebroside by macrophages results in hepatosplenomegaly (which may be massive), bleeding disorders and bone disease. The rate of splenic enlargement indicates the progression of the disease. Accumulation of glucocerebroside in the spleen contributes to the anaemia, thrombocytopenia and bleeding disorders commonly seen in patients with Gaucher’s disease.

Bone disease is a major source of discomfort and disability. ‘Bone crises’ (periods of intense pain due to bone infarction) require intravenous narcotic analgesia. Failure of bone remodelling, growth retardation and spontaneous fractures may occur as a result of bony pathology. In addition, a number of other body systems may be affected by Gaucher’s disease. Pulmonary, cardiac, renal, and gastrointestinal dysfunction have been reported, as well as lymphadenopathy and yellow-brown skin pigmentation. Fatigue is a common finding, possibly due to a raised resting metabolic rate caused by the accumulation of glucocerebroside.

Three main types ofGaucher’s disease have been identified. Type 1 Gaucher’s disease is characterised by the lack of neurological involvement and a chronic time course. With a prevalence of 1 in 40 000 in the general population and a carrier rate of 1 in 31 in East European Jews (Ashkenazim) in the US, type 1 disease is the most common form, accounting for approximately 99% of cases. Type 2 disease is the most severe neuronopathic form, and generally results in death within the first 2 years of life. Type 3 disease typically begins in early childhood and shares characteristics of both types 1 and 2. Types 2 and 3 are universally rare (≤1 in 100 000 population), except for an isolated group of patients with type 3 disease in Norrbotten, Sweden. Estimates suggest 1780 to 11 200 patients with type 1 disease in the US may be candidates for enzyme replacement therapy.

Therapeutic Efficacy and Tolerability

Alglucerase reduces organ enlargement, improves haematological parameters, and in the long term may improve bone architecture. Typically, improvements in organomegaly are the first to occur, with 20% reduction in liver volume and 35% reduction in splenic volume expected within the first year of treatment. Significant changes are usually evident within the first 6 months of therapy. Haematological parameters are slower to respond, but in most anaemic patients an increase in haemoglobin levels of 15 g/L may be expected in the initial treatment year. Platelet counts in patients with severe thrombocytopenia may double or be expected to normalise in patients with mild thrombocytopenia over the same treatment period. Bone pain usually reduces in severity and frequency within the first year of treatment but radiographical changes in bony architecture are rarely evident within this time-frame. A preliminary report of a single comparative trial between alglucerase and a recombinant enzyme preparation (imiglucerase) indicated that there was no difference in efficacy between these agents.

Alglucerase is generally well tolerated, with infrequent adverse effects usually related to the method of administration (e.g. inflammation at the intravenous catheter site) rather than to the drug itself. Seroconversion occurs in approximately 15% of patients but does not appear to alter the efficacy of alglucerase or necessitate treatment withdrawal. Episodes of pruritus or urticaria during infusion occur rarely and may be prevented with oral antihistamine agents.

Although formal studies have not been performed, patients treated with alglucerase appear to experience improved quality of life. Energy levels rise, and patients are able to resume work or school. Improvements in symptomatology, for example epistaxis, bruising, fatigue and pain, typically precede changes in physical and laboratory parameters.

Pharmacoeconomic Considerafions

The severity of Gaucher’s disease is highly variable and is only partially correlated with the patient’s genotype. Nonetheless, genetic services form an indispensable part of the costs of the disease. Although no specific data are available for the cost of genetic services for patients with Gaucher’s disease, genetic counselling sessions in the US cost between $US45 and $US89 per outpatient visit in 1984.

Other costs of illness may include splenectomy, blood transfusion, analgesia and orthopaedic procedures. Average direct and indirect costs for total hip joint replacement (a procedure frequent1y performed in patients with Gaucher’s disease) were estimated to be $Can9990 (1988 Canadian dollars). These costs are likely to be greater for patients with Gaucher’s disease as the risks of haemorrhage and infection are high in these patients. Charges for splenectomy in children with chronic immunothrombocytic purpura in the US ranged from $US5000 to $US30 000 in 1986. Pamidronic acid therapy has proved useful in alleviating bone disease in preliminary studies. However, cost data for this and other palliative treatments are unavailable.

Bone marrow transplantation has been performed in a limited number of patients with type l and 3 disease. Most surviving patients had subsequent complications that included mild graft-versus-host disease, or cerebral or pulmonary dysfunction. Allogeneic bone marrow transplantation has been estimated to cost between £40 000 and £60 000 in the UK.

Alglucerase is clearly more expensive than other treatment options, as estimated acquisition costs of dosage regimens used in clinical trials vary between $US16 650 and $US133 200 for the initial 6-month treatment period in 1994 (assuming $US3.70 per unit of alglucerase and patient bodyweight of 50kg). These costs do not include administration or monitoring costs, which may add a significant cost to frequent1y-administered low-dosage regimens unless patients can be treated at home. Experience with maintenance therapy is lacking, but it is expected that high dosages will be able to be reduced to 25% of the initial regimen.

Minimal costs per quality-adjusted life year (QALY) for a 10-year treatment period were estimated as $US147 000 for high-dose regimen of alglucerase 60 IU/kg bodyweight administered once every 2 weeks, compared with $US49 000 for alglucerase 2.3 IU/kg administered 3 times per week. These costs included some administration costs but assumed that immediate death would result from no treatment, which suggests that actual costs per QALY for patients with type l disease (which is not usually fatal) would be considerably higher.

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References

  1. Go1dman DP, C1arke AE, Garber AM. Creating the cost1iest orphan. The Orphan Drug Act in the deve10pment ofCeredase. Int J Technol Assess Health Care 1992 Fall; 8: 583–97

    Article  PubMed  CAS  Google Scholar 

  2. Syrop J. The worlds cost1iest drug: conflict overshadows cure. P&T 1994 Mar: 286–91

  3. WilIiams R. Can we afford medicaI advances? J R ColI Physicians Lond 1993 Jan; 27: 70-2

  4. Christomanou H, Chabas A, Pampo1s T, et al. Activator protein deficient Gauchers disease: a second patient with the new1y identified lipid storage disorder. K1in Wochenschr 1989; 67: 999-1003

    Google Scholar 

  5. Whittington R, Goa KL. Alglucerase: a review of its therapeutic use in Gaucher’s disease. Drugs 1992 Jul; 44: 72–93

    Article  PubMed  CAS  Google Scholar 

  6. Barranger JA, Ginns EJ. Glucosylceramide lipidoses: Gaucher disease. In: Scriver CR, Beaudet AL, Sly WS, et al., editors. The metabolic basis of inherited disease. 6th ed. New York: Mcgraw—Hill, 1989: 1677–98

    Google Scholar 

  7. Patterson MC, Horowitz M, Abel RB, et al. Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvementin Gaucher’s disease. Neurology 1993 Oct; 43 (10): 1993–7

    Article  PubMed  CAS  Google Scholar 

  8. Beutler E, Garber AM. Alglucerase for Gaucher’s disease: dose, costs and benefits. PharmacoEconomics 1994; 5: 453–9

    Article  PubMed  CAS  Google Scholar 

  9. Dahl N, Erikson A. Mutation diagnostics and Gaucher’s disease type III; a simple technique for risk evaluation [in Swedish]. Lakartidningen 1991; 88 (5): 313–5

    PubMed  CAS  Google Scholar 

  10. Hirano M, Ino T, Matsui T, et al. A 3 cases of Gaucher’s disease (adult type), with reference to cases reported in lapan (19701981)[in Japanese]. Rinsho Ketsueki 1984 Jul; 25: 1116–26

    PubMed  CAS  Google Scholar 

  11. Beutler E, Nguyen NJ, Henneberger MW, et al. Gaucher disease: gene frequencies in the Ashkenazi lewish popuIation. Am J Hum Genet 1993; 52: 85–8

    PubMed  CAS  Google Scholar 

  12. Goldblatt J, Beighton P. South African variants of Gaucher disease. Prog Clin Biol Res 1982; 95: 95–106

    PubMed  CAS  Google Scholar 

  13. Matoth Y, Chazan S, Cnaan A, et al. Frequency of carriers of chronic (type I) Gaucher disease in Ashkenazi jews. Am J Med Genet 1987 Jul; 27: 561–5

    Article  PubMed  CAS  Google Scholar 

  14. Beutler E, Gelbart T. Gaucher disease mutations in non—lewish patients. Br J Haematol 1993; 85: 401–5

    Article  PubMed  CAS  Google Scholar 

  15. Aerts JMFG, Donker-Koopman WE, Brul S, et al. Comparative study on glucocerebrosidase in spleens from patients withGaucher disease. Biochem J 1990; 269: 93–100

    PubMed  CAS  Google Scholar 

  16. James SP, Stromeyer FW, Chang C, et al. Liver abnormalities in patients with Gaucher’s disease. Gastroenterology 1981; 80: 126–33

    PubMed  CAS  Google Scholar 

  17. Kolodny EH, Ullman MD, Mankin HJ, et al. Phenotypic manifestations of Gaucher’s disease: clinical features in 48 biochemically verified type 1 patients and comment on type 2 patients. In: Desnick RJ, Gatt S, Grabowski GA, editors. Gaucher disease: a century of deIineation and research. NewYork: Alan R Liss, 1982: 33–65

    Google Scholar 

  18. Mankin HJ, Doppelt SH, Rosenberg AE, et al. Metabolic bone disease in patients with Gaucher’s disease. In: Avioli LV, Krane SM, editors. Metabolic bone disease and clinicalIy relateddisorders. 2nd ed. Philadelphia: WB Saunders, 1990: 730–49

    Google Scholar 

  19. Erikson A, Groth CG, Mansson J—E, et al. ClinicaI and biochemical outcome of marrow transplantation for Gaucher diseaseofthe Norrbottnian type. Acta Paediatr Scand 1990; 79: 680–5

    Article  PubMed  CAS  Google Scholar 

  20. Abella E, Smietana S, Bawle E, et al. Treatment of neuronopathic [NP] Gaucher’s disease [GD] with high dose mannoseterminaI glucocerebrosidase (M—GC):. Pediatr Res 1993 Apr; 33 (Part 2): 124A

    Google Scholar 

  21. Beutler E. Gaucher’s disease. N Engl J Med 1991; 325: 1354–60

    Article  PubMed  CAS  Google Scholar 

  22. ShoenfeId Y, Gallant LA, Shaklai M, et al. Gaucher’s disease: a disease with chronic stimulation of the immune system. Arch PathoI Lab Med 1982; 106: 388–91

    CAS  Google Scholar 

  23. Zimran A, Abrahamov A, Aker M, et al. Correction ofneutrophil chemotaxis defect in patients with Gaucher disease by lowdoseenzyme replacement therapy. Am J Hematol 1993 May; 43: 69–71

    Article  PubMed  CAS  Google Scholar 

  24. Barton DJ, Ludman MD, Benkov K, et al. Resting energy expenditure in Gaucher’s disease type I: effect of Gaucher’s cellburden on energy requirements. Metabolism 1989 Dec; 38: 1238–43

    Article  PubMed  CAS  Google Scholar 

  25. Verderese CL, Graham OC, Holder-McShane CA, et al. Gaucher’s disease: a pilot study ofthe symptomatic responsesto enzyme replacement therapy. J Neurosci Nurs 1993 Oct; 25: 296–301

    Article  PubMed  CAS  Google Scholar 

  26. Biswas SK, Pal NC, Sen NN, et al. Gaucher’s disease. Indian 1 Pathol Bacteriol 1968 Jul; 1l: 194–201

    Google Scholar 

  27. Dahl N, Hillborg PO, Olofsson A. Gaucher disease (Norrbottnian type III): probable founders identified by genealogical andmolecular studies. Hum Genet 1993 Nov; 92 (5): 513–5

    Article  PubMed  CAS  Google Scholar 

  28. Sibille A, Eng CM, Kim SJ, et al. Phenotype/genotype correlations in Gaucher disease type I: clinical and therapeutic implications. Am J Hum Genet 1993; 52 (6): 1094–101

    PubMed  CAS  Google Scholar 

  29. 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: 1464–70

    Article  PubMed  CAS  Google Scholar 

  30. Theophilus B, Latham T, Grabowski GA, et al. Gaucher disease: molecular heterogeneity and phenotype—genotype correlations. Am J Hum Genet 1989; 45: 212–25

    PubMed  CAS  Google Scholar 

  31. Zimran A, Gross E, West C, et al. Prediction of severity of Gaucher’s disease by identification of mutations at DNAlevel. Lancet 1989; 2: 349–52

    Article  PubMed  CAS  Google Scholar 

  32. Zimran A, Horowitz M. RecTL: a complex allele of the glucocerebrosidase gene associated with a mild clinicalcourse of Gaucher disease. Am J Med Genet 1994 Mar I; 50(I): 74–8

    Article  Google Scholar 

  33. Lewis BD, Nelson PV, Robertson EF, et al. Mutation analysis of 28 Gaucher disease patients: the Australasian experience. Am 1 Med Genet 1994 Jan 15; 49 (2): 218–23

    Article  CAS  Google Scholar 

  34. Kawame H, Maekawa K, Eto Y. Molecular screening of lapanese patients with Gaucher disease: phenotypic variability inthe same genotypes. Hum Mutat 1993; 2 (5): 362–7

    Article  PubMed  CAS  Google Scholar 

  35. Sidransky E, Bottler A, Stubblefield B, et al. DNA mutational analysis of type l and type 3 Gaucher patients: how well domutations predict phenotype? Hum Mutat 1994; 3 (l): 25–8

    Article  PubMed  CAS  Google Scholar 

  36. Pastores GM, Sibille AR, Grabowski GA. Enzyme therapy in Gaucher disease type l: dosage efficacy and adverse effectsin 33 patients treated for 6 to 24 months. Blood 1993 Jul 15; 82: 408–16

    PubMed  CAS  Google Scholar 

  37. Masuno M, Tomatsu S, Sukegawa K, et al. Non—existence of a tight association between a 4441eucine to proline mutationand phenotypes of Gaucher disease: high frequency of a Ncilpolymorphism in the non—neuronopathic form. Hum Genet 1990; 84 (2): 203–6

    Article  PubMed  CAS  Google Scholar 

  38. Bernhardt BA, Pyeritz RE. The organization and delivery of clinical genetics services. Pediatr Clin North Am 1992; 39: 1–12

    PubMed  CAS  Google Scholar 

  39. Myers TL, Prouty LA. Consumer costs for genetic services. Am J Med Genet 1987; 26: 521–30

    Article  PubMed  CAS  Google Scholar 

  40. Aerts JM, Donker-Koopman WE, Murray GJ, et al. Aprocedure for the rapid purification in high yield of human glucocerebrosidaseusing immunoaffinity chromatography withmonoclonal antibodies. Anal Biochem 1986; 154: 655–63

    Article  PubMed  CAS  Google Scholar 

  41. Aerts JM, Donker-Koopman WE, Koot M, et al. Deficient activity of glucocerebrosidase in urine from patients with typel Gaucher disease. Clin Chim Acta 1986; 158: 155–63

    Article  PubMed  CAS  Google Scholar 

  42. Barns RJ, Clague AE. An improved procedure for diagnosis of Gaucher disease using cultured skin fibroblasts and the chromogenicsubstrate, 2—hexadecanoylamino—4—nitrophenyl—o—glucopyranoside. Clin Chim Acta 1982; 120: 57–63

    Article  PubMed  CAS  Google Scholar 

  43. Midorikawa M, Okada S, Yutaka T, et al. Assay of glucocerebrosidase using a fluorescent analogue of glucocerebroside for the diagnosis of Gaucher disease. Biochem Int 1985; 11: 327–32

    PubMed  CAS  Google Scholar 

  44. Dinur T, Grabowski GA, Desnick RJ, et al. Synthesis of a fluorescent derivative of glucosyl ceramide for the sensitive determinationof glucocerebrosidase activity. Anal Biochem 1984; 136: 223–34

    Article  PubMed  CAS  Google Scholar 

  45. Choy FY. Intrafamilial clinical variability of type I Gaucher disease in a French—Canadian family. J Med Genet 1988; 25: 322–5

    Article  PubMed  CAS  Google Scholar 

  46. Lacerda L, Amaral O, Pinto R, et al. Identification of Gaucher disease carriers: glucocerebrosidase antigen and DNA analysis. Biochem Med Metab Biol 1993 Oct; 50 (2): 190–6

    Article  PubMed  CAS  Google Scholar 

  47. Beutler E, Saven A. Misuse of marrow examination in the diagnosis of Gaucher disease. Blood 1990; 76: 646–8

    PubMed  CAS  Google Scholar 

  48. Hollak CEM, van Weely S, van Oers MHJ, et al. Marked elevation of plasma chitotriosidase activity: a novel hallmark ofGaucher disease. J Clin Invest 1994 Mar; 93 (3): 1288–92

    Article  PubMed  CAS  Google Scholar 

  49. Fleshner PR, Aufses AH Jr, Grabowski GA, et al. A 27—year experience with splenectomy for Gaucher’s disease. Am J Surg 1991; 161: 69–75

    Article  PubMed  CAS  Google Scholar 

  50. Erikson A, Karlberg J, Skogman A—L, et al. Gaucher disease (type III): intellectual profile. Pediatr Neurol 1987; 3 (2): 87–91

    Article  PubMed  CAS  Google Scholar 

  51. Lee RE. The pathology of Gaucher disease. In: Desnick RJ, Gatt S, Grabowski GA, editors. Gaucher disease: a century of delineationand research. New York: Alan R Liss, 1982: 177–217

    Google Scholar 

  52. Fleshner PR, Astion DJ, Ludman MD, et al. Gaucher disease: fate of the splenic remnant after partial splenectomy — a caseofrapid enlargement. J Pediatr Surg 1989 Jun; 24 (6): 610–2

    Article  PubMed  CAS  Google Scholar 

  53. Bar-Maor JA. Partial splenectomy in Gaucher’s disease: follow— up report. J Pediatr Surg 1993; 28 (5) May: 686–8

    Article  PubMed  CAS  Google Scholar 

  54. Hollenberg JP, Subak LL, Ferry JJ Jr, et al. Cost—effectiveness of splenectomy versus intravenous gamma globulin in treatmentof chronic immune thrombocytopenic purpura in childhood. J Pediatr 1988; 112: 530–9

    Article  PubMed  CAS  Google Scholar 

  55. van Wellen PA, Haentjens P, Frecourt N, et al. Loosening of a noncemented porous—coated anatomic femoral component inGaucher’s disease. Acase report and review ofliterature. ActaOrthop Belg 1994; 60 (l): 119–23

    PubMed  Google Scholar 

  56. Rorabeck CH, Bourne RB, Laupacis A, et al. A double—blind study of 250 cases comparing cemented with cementless total hip arthroplasty. Clin Orthop Relat Res 1994 Jan (298): 156–64

    PubMed  Google Scholar 

  57. Samuel R, Katz K, Papapoulos SE, et al. Aminohydroxy propylidene bisphosphonate (APD) treatment improves the clinicalskeletal manifestations of Gaucher’s disease. Pediatrics 1994 Sep; 94 (3): 385–9

    PubMed  CAS  Google Scholar 

  58. Ostlere L, Warner T, Meunier PJ, et al. Treatment of type 1 Gaucher’s disease affecting bone with aminohydroxypropylidenebisphosphonate (pamidronate). Q J Med 1991 Jun; 79(290): 503–15

    Google Scholar 

  59. Harinck HIJ, Bijvoet OLM, van der Meer JWH, et al. Regression of bone lesions in Gaucher’s disease during treatmentwith aminohydroxypropylidene bisphosphonate [Ietter]. Lancet 1984; 1: 513

    Article  Google Scholar 

  60. Bembi B, Agosti E, Boehm P, et al. Aminohydroxypropylidenebiphosphonate in the treatment of bone lesions in a case ofGaucher’s disease type 3. Acta Paediatr 1994 Jan; 83 (1): 122–4

    Article  PubMed  CAS  Google Scholar 

  61. A 1994 Physician’s Gen Rx. New York: Data Pharmaceutica Inc.,1994

  62. Hobbs JR, Shaw PJ, Jones KH, et al. BeneficiaI effect of pretransplant splenectomy on displacement bone marrow transplantationfor Gaucher’s syndrome. Lancet 1987; 1: 1111–5

    Article  PubMed  CAS  Google Scholar 

  63. Rappeport JM, Ginns EJ. Bone—marrow transplantation in severe Gaucher’s disease. N Engl J Med 1984; 311: 84–8

    Article  PubMed  CAS  Google Scholar 

  64. Tsai P, Lipton JM, Sahdev I, et al. Allogenic bone marrow transplantation in severe Gaucher disease. Pediatr Res 1992 May; 31 (5): 503–7

    Article  PubMed  CAS  Google Scholar 

  65. Ringdén O, Groth CG, Erikson A, et al. Ten years’ experience of bone marrow transplantation for Gaucher disease. Transplantation. In press

  66. Dufoir T, Saux M—C, Terraza B, et al. Comparative cost of allogeneic or autologous bone marrow transplantation and chemotherapyin patients with acute myeloid leukaemia in firstremission. Bone Marrow Transplant 1992; 10: 323–9

    PubMed  CAS  Google Scholar 

  67. Goldman JM. Bone marrow transplantation in Europe — can the geographical differences be explained? J Intern Med 1993; 233: 311–3

    Article  PubMed  CAS  Google Scholar 

  68. Figueroa ML, Rosenbloom BE, Kay AC, et al. A less costly regimen of alglucerase to treat Gaucher’s disease. N Engl J Med 1992; 327: 1632–6

    Article  PubMed  CAS  Google Scholar 

  69. Hobbs JR. Current treatment for Gaucher’s disease. In: Hobbs JR, Riches PG, editors. Correction of certain genetic diseasesby transplantation 1991. London: COGENT, 1992: 30–7

    Google Scholar 

  70. Desnick SJ, Desnick RJ, Brandy RO, et al. Renal transplantation in type II Gaucher disease. Birth Defects 1973; 9: 109–19

    PubMed  CAS  Google Scholar 

  71. Groth CG, Bergstrom K, ColIste L, et al. Immunologic and plasma protein studies in a splenic homograft recipient. ClinExp Immunol 1972; 10: 359–65

    PubMed  CAS  Google Scholar 

  72. Carlson DE, Busuttil RW, Giudici TA, et al. Orthotopic liver transplantation in the treatment of complications of type IGaucher disease. Transplantation 1990 Jun; 49 (6): 1192–4

    Article  PubMed  CAS  Google Scholar 

  73. Starzl TE, Demetris AJ, Trucco M, et al. Chimerism after Iiver transplantation for type IV glycogen storage disease and typeI Gaucher’s disease. N Engl J Med 1993; 328: 745–9

    Article  PubMed  CAS  Google Scholar 

  74. Ducer FC, Bancel B, Caillon P, et al. Orthotopic Iiver transplantation for type I Gaucher’s disease. Transplantation 1992 May; 53 (5): 1141–3

    Article  Google Scholar 

  75. Smanik EJ, Tavill AS, Jacobs GH, et al. Orthotopic liver transplantation in two adults with Niemann—Pick and Gaucher’sDiseases: implications for the treatment of inherited metabolicdisease. Hepatology 1993 Jan; 17 (1): 42–9

    Article  PubMed  CAS  Google Scholar 

  76. Evans RW, Manninen DL, Dong FB, et al. Is retransplantation cost effective? Transplant Proc 1993; 25: 1694–6

    PubMed  CAS  Google Scholar 

  77. Barranger JA. Gaucher’s disease: new hope for treatment [Ietter]. Lancet 1993 Nov 27; 342: 1372

    Google Scholar 

  78. Zimran A, Elstein D, Kannai R, et al. Low—dose enzyme replacement therapy for Gaucher’s disease: effects of age, sex, genotype,and clinical features on response to treatment. Am J Med 1994 Jul; 97: 3–13

    Article  PubMed  CAS  Google Scholar 

  79. Fallet S, Grace ME, Sibille A, et al. Enzyme augmentation in moderate to life—threatening Gaucher disease. Pediatr Res 1992; 31: 496–502

    PubMed  CAS  Google Scholar 

  80. Barton NW, Brady RO, Dambrosia JM. Treatment of Gaucher’s disease [Ietter]. N Engl J Med 1993 May 27; 328: 1564–5

    Article  PubMed  CAS  Google Scholar 

  81. Beutler E, Kay A, Saven A, et al. Enzyme replacement therapy for Gaucher disease. Blood 1991; 78: 1183–9

    PubMed  CAS  Google Scholar 

  82. Hollak CEM, Aerts JMFG, van Oers MHJ. Treatment of Gaucher’s disease [Ietter]. N Engl J Med 1993; 328: 1565–6

    PubMed  CAS  Google Scholar 

  83. Barton NW, Brady RO, Dambrosia JM, et al. Dose—dependent responses to macrophage—targeted glucocerebrosidase in achild with Gaucher disease. J Pediatr 1992; 120: 277–80

    Article  PubMed  CAS  Google Scholar 

  84. Mistry PK, Davies S, Corfield A, et al. Successful treatment of bone marrow failure in Gaucher’s disease with low—dose modifiedglucocerebrosidase. QJ Med 1992 Jul; 83: 541–6

    CAS  Google Scholar 

  85. Barton NW, Brady RO. Gaucher disease: skeletal responses to enzyme replacement therapy. Gaucher Clinical Perspectives 1994 Sep; 2: 8–11

    Google Scholar 

  86. Sidransky E, Ginns EJ, Westman JA, et al. Pathologic fractures may develop in Gaucher patients receiving enzyme replacementtherapy [Ietter]. Am J Hematol 1994 Oct; 47: 248–9

    Google Scholar 

  87. Freiwald DR. Treatment ofGaucher’s disease [Ietter]. N Engl J Med 1993; 328: 1566

    PubMed  CAS  Google Scholar 

  88. Mìstry PK, Wraight EP, Cox TM. Tissue distribution and metabolism of placental and recombinant mannose—terminatedglucocerebrosidase in Gaucher’s disease [abstract]. FirstWorkshop of the European Working Group on Gaucher Disease. 1994 Oct 13-16; Trieste, Italy, 51.

    Google Scholar 

  89. Erikson A, Johansson K, Mansson JE, et al. Enzyme replacement therapy of infantile Gaucher disease. Neuropediatrics 1993 Aug; 24 (4): 237–8

    Article  PubMed  CAS  Google Scholar 

  90. Grabowski GA, Pastores G, Brady RO, et al. Gaucher disease type I: safety and efficacy of macrophage-targeted recombinantglucocerebrosidase therapy [abstract]. Pediatr Res 1993 Apr; 33 (Part 2): 139

    Google Scholar 

  91. Zimran A, Hollak CEM, Abrahamov A, et al. Home treatment with intravenous enzyme replacement therapy for Gaucherdisease: an international collaborative study of 33 patients. Blood 1993 Aug 15; 82: 1107–9

    PubMed  CAS  Google Scholar 

  92. Brady RO, Barton NW. Enzyme replacement therapy for Gaucher disease: criticaI investigations beyond demonstrationof clinical efficacy. Biochem Med Metab Biol 1994; 52: 1–9

    Article  PubMed  CAS  Google Scholar 

  93. Beutler E, Figueroa M, Koziol J. Treatment of Gaucher’s disease. Reply [Ietter]. N Engl J Med 1993 May 27; 328: 1567

    Google Scholar 

  94. Zimran A, Elstein D, Levy-Lahad E, et al. Preliminary report of low—dose enzyme replacement therapy with human recombinantglucocerebrosidase in Gaucher disease [abstract no.1038]. Am J Hum Genet 1994 Sep; 55 Suppl.: A179

    Google Scholar 

  95. Data on file, Genzyme Corporation 1992.

  96. Syrop J. The world’s costliest drug: conflict overshadows cure. Drug Ther 1993 Sep; 23: 47–9

    Google Scholar 

  97. Bansal V, Mowery-Rushton PA, Lucht L, et al. Retroviral transduction of myoblasts with human glucocerebrosidase gene forsystemic delivery of glucocerebrosidase [abstract]. Br J HumGen 1993; 53 Suppl.: 104

    Google Scholar 

  98. Laupacis A, Feeny D, Detsky AS, et al. How attractive does a new technology have to be to warrant adoption and utilization?Tentative guidelines for using clinical and economicevaluations. Can Med Assoc J 1992; 146: 473–81

    Google Scholar 

  99. Eddy DM. Rationing resources while improving quality: how to get more for less. JAMA 1994 Sep 14; 272 (IO): 817-24

  100. Eddy DM. Principles for making difficult decisions in difficult times. JAMA 1994 Jun 8; 271 (22): 1792–8

    Article  PubMed  CAS  Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag No. 65901, Mairangi Bay, Auckland 10, New Zealand

    Ruth Whittington & Karen L. Goa

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  1. Ruth Whittington
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  2. Karen L. Goa
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Various sections of the manuscript reviewed by: N.W. Barton, Clinical Investigations Section, Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA; E. Beutler, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California, USA; A. Bomford, Institute of Liver Studies, King’s College School of Medicine and Dentistry, London, England; T.M. Cox, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, England; C.A. Crabowski, College of Medicine, University of Cincinnati, Cincinnati, USA; R.I. Parker, Department of Pediatrics, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York, USA; O. Ringdén, Department of Transplantation Surgery, Huddinge Hospital, Stockholm, Sweden; Z. Yosipovitch,Department of Orthopedics, Beilinson Medical Center, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, Israel; A. Zimran, Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.

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Whittington, R., Goa, K.L. Alglucerase. Pharmacoeconomics 7, 63–90 (1995). https://doi.org/10.2165/00019053-199507010-00007

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