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Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease.
Am J Hematol. 2015 Jul; 90(7):592-7.AJ

Abstract

Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 × 10(9) /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for anti-imiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes.

Authors+Show Affiliations

Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.Department of Haematology, Royal Free Hospital, London, United Kingdom. Department of Haematology, University College London, London, United Kingdom.Department of Haematology, Royal Free Hospital, London, United Kingdom. Department of Haematology, University College London, London, United Kingdom.Medicina Metabólica Hereditaria, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain. Grupo de Estudio de Enfermedades Hematologícas y Metabolicas, Hospital Universitario Miguel Servet, Zaragoza, Spain.Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.Departments of Human Genetics and Ophthalmology, School of Medicine, Emory University, Atlanta, Georgia.Department of Biomedical, Industrial, & Human Factors Engineering, Wright State University, Dayton, Ohio.Bioanalytical and BioMarker Development, Shire, Lexington, Massachusetts.Biostatistics & Statistical Programming Department, Shire, Lexington, Massachusetts.Rare Disease Unit, Shire, Lexington, Massachusetts.Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25776130

Citation

Elstein, Deborah, et al. "Safety and Efficacy Results of Switch From Imiglucerase to Velaglucerase Alfa Treatment in Patients With Type 1 Gaucher Disease." American Journal of Hematology, vol. 90, no. 7, 2015, pp. 592-7.
Elstein D, Mehta A, Hughes DA, et al. Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease. Am J Hematol. 2015;90(7):592-7.
Elstein, D., Mehta, A., Hughes, D. A., Giraldo, P., Charrow, J., Smith, L., Shankar, S. P., Hangartner, T. N., Kunes, Y., Wang, N., Crombez, E., & Zimran, A. (2015). Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease. American Journal of Hematology, 90(7), 592-7. https://doi.org/10.1002/ajh.24007
Elstein D, et al. Safety and Efficacy Results of Switch From Imiglucerase to Velaglucerase Alfa Treatment in Patients With Type 1 Gaucher Disease. Am J Hematol. 2015;90(7):592-7. PubMed PMID: 25776130.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease. AU - Elstein,Deborah, AU - Mehta,Atul, AU - Hughes,Derralynn A, AU - Giraldo,Pilar, AU - Charrow,Joel, AU - Smith,Laurie, AU - Shankar,Suma P, AU - Hangartner,Thomas N, AU - Kunes,Yune, AU - Wang,Nan, AU - Crombez,Eric, AU - Zimran,Ari, PY - 2014/11/21/received PY - 2015/02/20/revised PY - 2015/03/10/accepted PY - 2015/3/18/entrez PY - 2015/3/18/pubmed PY - 2015/9/2/medline SP - 592 EP - 7 JF - American journal of hematology JO - Am. J. Hematol. VL - 90 IS - 7 N2 - Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 × 10(9) /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for anti-imiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes. SN - 1096-8652 UR - https://www.unboundmedicine.com/medline/citation/25776130/Safety_and_efficacy_results_of_switch_from_imiglucerase_to_velaglucerase_alfa_treatment_in_patients_with_type_1_Gaucher_disease_ L2 - https://doi.org/10.1002/ajh.24007 DB - PRIME DP - Unbound Medicine ER -