Journal of Genetic Medicine

  • 제17권2호
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  • Pages.62-67
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  • 2020
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  • 1226-1769(pISSN)
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  • 2383-8442(eISSN)
대한의학유전학회 (Korean Society of Medical Genetics and Genomics)
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One-year experience of oral substrate reduction therapy in three patients with Gaucher disease type I

  • Sohn, Young Bae (Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Kim, Yewon (Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Moon, Ji Eun (Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine)
  • 투고 : 2020.05.15
  • 심사 : 2020.06.12
  • 발행 : 2020.12.31
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초록

Purpose: Eliglustat is an oral substrate reduction therapy (SRT) approved for adults with Gaucher disease type I (GD1) who are extensive, intermediate, or poor CYP2D6 metabolizers. Here we report one-year experience of eliglustat switch therapy from long-term enzyme replacement therapy (ERT) in three adult patients with GD1. Materials and Methods: Medical history, clinical (hemoglobin concentration, platelet count, and bone mineral density) and biochemical parameters (angiotensin converting enzyme, total acid phosphatase, and lyso-gb1) of the patients were collected and evaluated by retrospective review of medical records at every 3, 6, or 12 month after switch to SRT. Results: Patient 1 was a 43-year old female diagnosed GD1 and her clinical and biochemical parameters were stabilized for more than 20 years by ERT. Due to the burden of regular hospital visit, she switched to SRT. During one-year of SRT, clinical parameters and biomarkers were maintained stable. However, after suffering acute febrile illness during SRT, she decided to re-switch to ERT due to concerns about drug interaction. Patient 2 was 41-year old male, younger brother of patient 1 and Patient 3 was 31-year old male. They switched to SRT in clinically stable condition with long-term ERT. The one-year SRT was tolerable without specific safety issue and the clinical parameters were maintained stable. Conclusion: One-year eliglustat therapy in three adult patients with GDI was generally tolerable and effective for maintaining the clinical parameters and biomarkers. However, the drug compliance, concurrent drug interactions, and long-term safety of eliglustat should be carefully monitored.

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참고문헌

  1. Grabowski GA, Petsko GA, Kolodny EH. Gaucher disease. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The online metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 2019.
  2. Cox TM, Cachon-Gonzalez MB. The cellular pathology of lysosomal diseases. J Pathol 2012;226:241-54. https://doi.org/10.1002/path.3021
  3. Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, et al. Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial. Lancet 2015;385:2355-62. https://doi.org/10.1016/S0140-6736(14)61841-9
  4. Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial. JAMA 2015;313:695-706. https://doi.org/10.1001/jama.2015.459
  5. Mistry PK, Lukina E, Ben Turkia H, Shankar SP, Baris H, Ghosn M, et al. Outcomes after 18 months of eliglustat therapy in treatment-naive adults with Gaucher disease type 1: the phase 3 ENGAGE trial. Am J Hematol 2017;92:1170-6. https://doi.org/10.1002/ajh.24877
  6. Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 2010;116:893-9. https://doi.org/10.1182/blood.v116.21.893.893
  7. Lukina E, Watman N, Dragosky M, Lau H, Avila Arreguin E, Rosenbaum H, et al. Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: final results from the phase 2 trial. Am J Hematol 2019;94:29-38. https://doi.org/10.1002/ajh.25300
  8. Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, et al. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood 2017;129:2375-83. https://doi.org/10.1182/blood-2016-12-758409
  9. Peterschmitt MJ, Freisens S, Underhill LH, Foster MC, Lewis G, Gaemers SJM. Long-term adverse event profile from four completed trials of oral eliglustat in adults with Gaucher disease type 1. Orphanet J Rare Dis 2019;14:128. https://doi.org/10.1186/s13023-019-1085-6
  10. Dekker N, van Dussen L, Hollak CE, Overkleeft H, Scheij S, Ghauharali K, et al. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood 2011;118:e118-27. https://doi.org/10.1182/blood-2011-05-352971
  11. Murugesan V, Chuang WL, Liu J, Lischuk A, Kacena K, Lin H, et al. Glucosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol 2016;91:1082-9. https://doi.org/10.1002/ajh.24491
  12. Rolfs A, Giese AK, Grittner U, Mascher D, Elstein D, Zimran A, et al. Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients. PLoS One 2013;8:e79732. https://doi.org/10.1371/journal.pone.0079732
  13. Elstein D, Mellgard B, Dinh Q, Lan L, Qiu Y, Cozma C, et al. Reductions in glucosylsphingosine (lyso-Gb1) in treatment-naive and previously treated patients receiving velaglucerase alfa for type 1 Gaucher disease: data from phase 3 clinical trials. Mol Genet Metab 2017;122:113-20. https://doi.org/10.1016/j.ymgme.2017.08.005
  14. Hurvitz N, Dinur T, Becker-Cohen M, Cozma C, Hovakimyan M, Oppermann S, et al. Glucosylsphingosine (lyso-Gb1) as a biomarker for monitoring treated and untreated children with Gaucher disease. Int J Mol Sci 2019;20:3033. https://doi.org/10.3390/ijms20123033
  15. Bennett LL, Turcotte K. Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease. Drug Des Devel Ther 2015;9:4639-47. https://doi.org/10.2147/DDDT.S77760
  16. Balwani M, Burrow TA, Charrow J, Goker-Alpan O, Kaplan P, Kishnani PS, et al. Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States. Mol Genet Metab 2016;117:95-103. https://doi.org/10.1016/j.ymgme.2015.09.002
  17. Belmatoug N, Di Rocco M, Fraga C, Giraldo P, Hughes D, Lukina E, et al. Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe. Eur J Intern Med 2017;37:25-32. https://doi.org/10.1016/j.ejim.2016.07.011