Maurizio Scarpa, George A. Diaz, Roberto Giugliani, Simon A. Jones, Eugen Mengel, Nathalie Guffon, Peter Witters, Jaya Ganesh, Nicole M. Armstrong, Shruti Srivastava, Yong Kim
{"title":"脂酶- α酶替代疗法治疗酸性鞘磷脂酶缺乏症儿童和青少年的长期安全性和临床结果","authors":"Maurizio Scarpa, George A. Diaz, Roberto Giugliani, Simon A. Jones, Eugen Mengel, Nathalie Guffon, Peter Witters, Jaya Ganesh, Nicole M. Armstrong, Shruti Srivastava, Yong Kim","doi":"10.1002/jimd.70086","DOIUrl":null,"url":null,"abstract":"<p>Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease characterized by hepatosplenomegaly, pulmonary dysfunction, dyslipidemia, and growth deficits. Olipudase alfa (recombinant-human ASM) is the only treatment for non-central-nervous-system ASMD manifestations in children and adults. An open-label long-term study followed 4 to 8 years of olipudase alfa treatment in 20 children and adolescents with ASMD (baseline age (years) 1.5–17.5). At final assessments, splenomegaly and hepatomegaly were reduced relative to baseline (mean percent decrease in spleen and liver volumes 78% ± 1.2% and 59.8% ± 1.5%, respectively). Baseline splenomegaly was severe (spleen volume > 15 MN [multiples of normal]) or moderate (5–15 MN) (<i>n</i> = 12 and <i>n</i> = 8, respectively) versus mild/absent (< 5 MN) (<i>n</i> = 12) or moderate (<i>n</i> = 8) at final assessment. Baseline hepatomegaly was severe (liver volume > 2.5 MN) (<i>n</i> = 10) or moderate (1.25–2.5 MN) (<i>n</i> = 10) versus mild/absent (< 1.25 MN) (<i>n</i> = 19) or moderate (<i>n</i> = 1) at final assessment. Among nine individuals able to perform assessments, diffusing capacity of the lung for carbon monoxide (DL<sub>CO</sub>) impairment was severe (< 40%) (<i>n</i> = 1), moderate (40%–60%) (<i>n</i> = 4), or mild (60%–80%) (<i>n</i> = 4) at baseline versus absent (<i>n</i> = 4), mild (<i>n</i> = 4) or moderate (<i>n</i> = 1) at final assessment. Mean percent increase in DL<sub>CO</sub> was 53.7% ± 6.5%. At baseline, 10/20 children had clinical short stature (height <i>Z</i>-scores ≤ − 2) at baseline versus 0/20 at the final assessment. Atherogenic lipid profiles and liver function tests normalized within 2 years and remained stable. Adverse events were mostly mild or moderate, with 4 individuals experiencing 7 serious adverse events, all recovered/resolved. Interpretation: Enzyme replacement therapy with olipudase alfa in children and adolescents with chronic ASMD was well-tolerated with clinically meaningful improvements in multiple disease parameters.</p><p><b>Trial Registration:</b> NCT02004704.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 5","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70086","citationCount":"0","resultStr":"{\"title\":\"Long-Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency\",\"authors\":\"Maurizio Scarpa, George A. Diaz, Roberto Giugliani, Simon A. Jones, Eugen Mengel, Nathalie Guffon, Peter Witters, Jaya Ganesh, Nicole M. Armstrong, Shruti Srivastava, Yong Kim\",\"doi\":\"10.1002/jimd.70086\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease characterized by hepatosplenomegaly, pulmonary dysfunction, dyslipidemia, and growth deficits. Olipudase alfa (recombinant-human ASM) is the only treatment for non-central-nervous-system ASMD manifestations in children and adults. An open-label long-term study followed 4 to 8 years of olipudase alfa treatment in 20 children and adolescents with ASMD (baseline age (years) 1.5–17.5). At final assessments, splenomegaly and hepatomegaly were reduced relative to baseline (mean percent decrease in spleen and liver volumes 78% ± 1.2% and 59.8% ± 1.5%, respectively). Baseline splenomegaly was severe (spleen volume > 15 MN [multiples of normal]) or moderate (5–15 MN) (<i>n</i> = 12 and <i>n</i> = 8, respectively) versus mild/absent (< 5 MN) (<i>n</i> = 12) or moderate (<i>n</i> = 8) at final assessment. Baseline hepatomegaly was severe (liver volume > 2.5 MN) (<i>n</i> = 10) or moderate (1.25–2.5 MN) (<i>n</i> = 10) versus mild/absent (< 1.25 MN) (<i>n</i> = 19) or moderate (<i>n</i> = 1) at final assessment. Among nine individuals able to perform assessments, diffusing capacity of the lung for carbon monoxide (DL<sub>CO</sub>) impairment was severe (< 40%) (<i>n</i> = 1), moderate (40%–60%) (<i>n</i> = 4), or mild (60%–80%) (<i>n</i> = 4) at baseline versus absent (<i>n</i> = 4), mild (<i>n</i> = 4) or moderate (<i>n</i> = 1) at final assessment. Mean percent increase in DL<sub>CO</sub> was 53.7% ± 6.5%. At baseline, 10/20 children had clinical short stature (height <i>Z</i>-scores ≤ − 2) at baseline versus 0/20 at the final assessment. Atherogenic lipid profiles and liver function tests normalized within 2 years and remained stable. Adverse events were mostly mild or moderate, with 4 individuals experiencing 7 serious adverse events, all recovered/resolved. 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Long-Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency
Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease characterized by hepatosplenomegaly, pulmonary dysfunction, dyslipidemia, and growth deficits. Olipudase alfa (recombinant-human ASM) is the only treatment for non-central-nervous-system ASMD manifestations in children and adults. An open-label long-term study followed 4 to 8 years of olipudase alfa treatment in 20 children and adolescents with ASMD (baseline age (years) 1.5–17.5). At final assessments, splenomegaly and hepatomegaly were reduced relative to baseline (mean percent decrease in spleen and liver volumes 78% ± 1.2% and 59.8% ± 1.5%, respectively). Baseline splenomegaly was severe (spleen volume > 15 MN [multiples of normal]) or moderate (5–15 MN) (n = 12 and n = 8, respectively) versus mild/absent (< 5 MN) (n = 12) or moderate (n = 8) at final assessment. Baseline hepatomegaly was severe (liver volume > 2.5 MN) (n = 10) or moderate (1.25–2.5 MN) (n = 10) versus mild/absent (< 1.25 MN) (n = 19) or moderate (n = 1) at final assessment. Among nine individuals able to perform assessments, diffusing capacity of the lung for carbon monoxide (DLCO) impairment was severe (< 40%) (n = 1), moderate (40%–60%) (n = 4), or mild (60%–80%) (n = 4) at baseline versus absent (n = 4), mild (n = 4) or moderate (n = 1) at final assessment. Mean percent increase in DLCO was 53.7% ± 6.5%. At baseline, 10/20 children had clinical short stature (height Z-scores ≤ − 2) at baseline versus 0/20 at the final assessment. Atherogenic lipid profiles and liver function tests normalized within 2 years and remained stable. Adverse events were mostly mild or moderate, with 4 individuals experiencing 7 serious adverse events, all recovered/resolved. Interpretation: Enzyme replacement therapy with olipudase alfa in children and adolescents with chronic ASMD was well-tolerated with clinically meaningful improvements in multiple disease parameters.
期刊介绍：
The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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