Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis
Abstract Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that is characterized by accumulation of cysteine and formation of crystals within cells of different organs and tissues causing systemic manifestations in childhood that include poor linear growth, ocular invol...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12260 |
| _version_ | 1798034341989711872 |
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| author | Maria Helena Vaisbich Juliana Caires Ferreira Heather Price Kyleen D. Young Saba Sile Gregg Checani Craig B. Langman |
| author_facet | Maria Helena Vaisbich Juliana Caires Ferreira Heather Price Kyleen D. Young Saba Sile Gregg Checani Craig B. Langman |
| author_sort | Maria Helena Vaisbich |
| collection | DOAJ |
| description | Abstract Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that is characterized by accumulation of cysteine and formation of crystals within cells of different organs and tissues causing systemic manifestations in childhood that include poor linear growth, ocular involvement, hypothyroidism, and progressive kidney disease. This study was a long‐term, prospective open‐label evaluation of twice‐daily delayed release (DR) cysteamine capsules in cystinosis patients <6 years of age who were naïve to any form of cysteamine treatment. Fifteen treatment‐naïve patients <6 years old (mean age 2.2 ± 1.0 years, 53% male, 73% White) were enrolled and treated with DR‐cysteamine capsules for up to 18 months. Patients had clinically meaningful decreases in WBC cysteine concentration during treatment (3.2 ± 3.0 nmol ½ cystine/mg protein at Day 1 to 0.8 ± 0.8 nmol ½ cystine/mg protein at study exit), and anthropometric data improvements were consistently observed in height, weight and body surface area. Additionally, estimated glomerular filtration rate increased from 55.93 ± 22.43 ml/min/1.73 m2 at baseline to 63.79 ± 21.44 ml/min/1.73 m2 at study exit. Pharmacokinetic/Pharmacodynamic results support the use of the same starting, escalation, and maintenance doses according to body surface for children aged <6 years that are currently recommended in adults and older children. All patients experienced ≥1 adverse event(s) with vomiting (80%) and upper respiratory tract infection (53%) most frequently reported. Based on our study, patients <6 years of age with nephropathic cystinosis without prior treatment can safely and effectively initiate treatment with DR‐cysteamine, a delayed‐release form of cysteamine bitartrate that can be given every 12 h. |
| first_indexed | 2024-04-11T20:42:57Z |
| format | Article |
| id | doaj.art-d94e9d5fb4c941ffa28be53443ea2b05 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-04-11T20:42:57Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-d94e9d5fb4c941ffa28be53443ea2b052022-12-22T04:04:09ZengWileyJIMD Reports2192-83122022-01-01631667910.1002/jmd2.12260Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosisMaria Helena Vaisbich0Juliana Caires Ferreira1Heather Price2Kyleen D. Young3Saba Sile4Gregg Checani5Craig B. Langman6São Paulo University Medical School São Paulo BrazilInstituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) São Paulo BrazilAnn & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois USAAnn & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois USAHorizon Therapeutics plc Deerfield Illinois USAHorizon Therapeutics plc Deerfield Illinois USAFeinberg School of Medicine Northwestern University Chicago Illinois USAAbstract Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that is characterized by accumulation of cysteine and formation of crystals within cells of different organs and tissues causing systemic manifestations in childhood that include poor linear growth, ocular involvement, hypothyroidism, and progressive kidney disease. This study was a long‐term, prospective open‐label evaluation of twice‐daily delayed release (DR) cysteamine capsules in cystinosis patients <6 years of age who were naïve to any form of cysteamine treatment. Fifteen treatment‐naïve patients <6 years old (mean age 2.2 ± 1.0 years, 53% male, 73% White) were enrolled and treated with DR‐cysteamine capsules for up to 18 months. Patients had clinically meaningful decreases in WBC cysteine concentration during treatment (3.2 ± 3.0 nmol ½ cystine/mg protein at Day 1 to 0.8 ± 0.8 nmol ½ cystine/mg protein at study exit), and anthropometric data improvements were consistently observed in height, weight and body surface area. Additionally, estimated glomerular filtration rate increased from 55.93 ± 22.43 ml/min/1.73 m2 at baseline to 63.79 ± 21.44 ml/min/1.73 m2 at study exit. Pharmacokinetic/Pharmacodynamic results support the use of the same starting, escalation, and maintenance doses according to body surface for children aged <6 years that are currently recommended in adults and older children. All patients experienced ≥1 adverse event(s) with vomiting (80%) and upper respiratory tract infection (53%) most frequently reported. Based on our study, patients <6 years of age with nephropathic cystinosis without prior treatment can safely and effectively initiate treatment with DR‐cysteamine, a delayed‐release form of cysteamine bitartrate that can be given every 12 h.https://doi.org/10.1002/jmd2.12260anthropometric parameterschildrencysteinecystinosisdelayed‐release cysteamineimmediate‐release cysteamine |
| spellingShingle | Maria Helena Vaisbich Juliana Caires Ferreira Heather Price Kyleen D. Young Saba Sile Gregg Checani Craig B. Langman Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis JIMD Reports anthropometric parameters children cysteine cystinosis delayed‐release cysteamine immediate‐release cysteamine |
| title | Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis |
| title_full | Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis |
| title_fullStr | Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis |
| title_full_unstemmed | Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis |
| title_short | Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis |
| title_sort | cysteamine bitartrate delayed release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open label study of treatment naive patients 6 years of age with nephropathic cystinosis |
| topic | anthropometric parameters children cysteine cystinosis delayed‐release cysteamine immediate‐release cysteamine |
| url | https://doi.org/10.1002/jmd2.12260 |
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