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Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several cl...

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Autores principales: Pan, Yu-Wen, Tsai, Meng-Che, Yang, Chiao-Yu, Yu, Wen-Hao, Wang, Bow, Yang, Yao-Jong, Chou, Yen-Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979262/
https://www.ncbi.nlm.nih.gov/pubmed/36873248
http://dx.doi.org/10.1016/j.ymgmr.2023.100957
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author Pan, Yu-Wen
Tsai, Meng-Che
Yang, Chiao-Yu
Yu, Wen-Hao
Wang, Bow
Yang, Yao-Jong
Chou, Yen-Yin
author_facet Pan, Yu-Wen
Tsai, Meng-Che
Yang, Chiao-Yu
Yu, Wen-Hao
Wang, Bow
Yang, Yao-Jong
Chou, Yen-Yin
author_sort Pan, Yu-Wen
collection PubMed
description BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several clinical trials have reported promising safety and efficacy results in adult and pediatric patients. However, no data have been reported outside of the clinical trial setting yet. This study aimed to evaluate major outcomes in pediatric chronic ASMD patients receiving olipudase alfa in the real-world setting. MATERIALS AND METHODS: Two children with type A/B (chronic neuropathic) ASMD have received olipudase alfa treatment since May 2021. Clinical parameters, including height, weight, complete blood count, liver function tests, lipid profiles, biomarkers, abdominal ultrasonography with shear wave elastography, chest computed tomography, nerve conduction studies, neurodevelopmental evaluations, and six-minute walk tests, were checked at baseline and every three to six months in the first year of enzyme replacement therapy (ERT) to assess its efficacy and safety. RESULTS: The two patients in our study started olipudase alfa treatment at the age of 5 years and 8 months and 2 years and 6 months. During the first year of treatment, both patients saw a reduction in their hepatic and splenic volumes as well as liver stiffness. Height z-score, weight z-score, lipid profiles, biomarker levels, interstitial lung disease scores, and bone mineral densities also improved over time. The six-minute walk test showed a gradual increase in walking distance in both patients. There were no obvious improvements or deterioration in neurocognitive function and peripheral nerve conduction velocities after treatment. No severe infusion-associated reactions were noted during the first year of treatment. One patient had two episodes of transient but significantly elevated liver enzymes during the dose-escalation phase. The patient was asymptomatic, and the impaired liver function resolved spontaneously within two weeks. CONCLUSION: Our results provide real-world experience that olipudase alfa is safe and effective in improving major systemic clinical outcomes for pediatric chronic ASMD patients. Monitoring of liver stiffness by shear wave elastography is a noninvasive procedure that can monitor treatment efficacy during ERT.
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spelling pubmed-99792622023-03-03 Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan Pan, Yu-Wen Tsai, Meng-Che Yang, Chiao-Yu Yu, Wen-Hao Wang, Bow Yang, Yao-Jong Chou, Yen-Yin Mol Genet Metab Rep Research Paper BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several clinical trials have reported promising safety and efficacy results in adult and pediatric patients. However, no data have been reported outside of the clinical trial setting yet. This study aimed to evaluate major outcomes in pediatric chronic ASMD patients receiving olipudase alfa in the real-world setting. MATERIALS AND METHODS: Two children with type A/B (chronic neuropathic) ASMD have received olipudase alfa treatment since May 2021. Clinical parameters, including height, weight, complete blood count, liver function tests, lipid profiles, biomarkers, abdominal ultrasonography with shear wave elastography, chest computed tomography, nerve conduction studies, neurodevelopmental evaluations, and six-minute walk tests, were checked at baseline and every three to six months in the first year of enzyme replacement therapy (ERT) to assess its efficacy and safety. RESULTS: The two patients in our study started olipudase alfa treatment at the age of 5 years and 8 months and 2 years and 6 months. During the first year of treatment, both patients saw a reduction in their hepatic and splenic volumes as well as liver stiffness. Height z-score, weight z-score, lipid profiles, biomarker levels, interstitial lung disease scores, and bone mineral densities also improved over time. The six-minute walk test showed a gradual increase in walking distance in both patients. There were no obvious improvements or deterioration in neurocognitive function and peripheral nerve conduction velocities after treatment. No severe infusion-associated reactions were noted during the first year of treatment. One patient had two episodes of transient but significantly elevated liver enzymes during the dose-escalation phase. The patient was asymptomatic, and the impaired liver function resolved spontaneously within two weeks. CONCLUSION: Our results provide real-world experience that olipudase alfa is safe and effective in improving major systemic clinical outcomes for pediatric chronic ASMD patients. Monitoring of liver stiffness by shear wave elastography is a noninvasive procedure that can monitor treatment efficacy during ERT. Elsevier 2023-01-31 /pmc/articles/PMC9979262/ /pubmed/36873248 http://dx.doi.org/10.1016/j.ymgmr.2023.100957 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Pan, Yu-Wen
Tsai, Meng-Che
Yang, Chiao-Yu
Yu, Wen-Hao
Wang, Bow
Yang, Yao-Jong
Chou, Yen-Yin
Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title_full Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title_fullStr Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title_full_unstemmed Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title_short Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan
title_sort enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: a single center experience in taiwan
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979262/
https://www.ncbi.nlm.nih.gov/pubmed/36873248
http://dx.doi.org/10.1016/j.ymgmr.2023.100957
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