Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre
Abstract In urea cycle disorders (UCDs) ammonia scavenger drugs, usually sodium‐based, have been the mainstay of treatment. Increasingly, glycerol phenylbutyrate (GPB, Ravicti®) is being used but scant real‐world data exist regarding clinical outcomes. A retrospective study of UCD patients initiated...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12386 |
| _version_ | 1827822330943897600 |
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| author | Mildrid Yeo Preeya Rehsi Megan Dorman Stephanie Grunewald Julien Baruteau Anupam Chakrapani Emma Footitt Helen Prunty Melanie McSweeney |
| author_facet | Mildrid Yeo Preeya Rehsi Megan Dorman Stephanie Grunewald Julien Baruteau Anupam Chakrapani Emma Footitt Helen Prunty Melanie McSweeney |
| author_sort | Mildrid Yeo |
| collection | DOAJ |
| description | Abstract In urea cycle disorders (UCDs) ammonia scavenger drugs, usually sodium‐based, have been the mainstay of treatment. Increasingly, glycerol phenylbutyrate (GPB, Ravicti®) is being used but scant real‐world data exist regarding clinical outcomes. A retrospective study of UCD patients initiated on or switched to GPB was performed at a UK centre. Data on population characteristics, treatment aspects, laboratory measurements, and clinical outcomes were collected before and after patients started GPB with a sub‐group analysis undertaken for patients with ≥12 months of data before and after starting GPB. UCDs included arginosuccinate synthetase deficiency (n = 8), arginosuccinate lyase deficiency (n = 6), ornithine carbamoyltransferase deficiency (n = 3), and carbamoyl phosphate synthetase 1 deficiency (n = 3). In the sub‐group analysis (n = 11), GPB resulted in lower plasma ammonia (31 vs. 41 μmol/L, p = 0.037), glutamine (670 vs. 838 μmol/L, p = 0.002), annualised hyperammonaemic episodes (0.2 vs. 1.9, p = 0.020), hospitalisations (0.5 vs. 2.2, p = 0.010), and hyperammonaemic episodes resulting in hospitalisation (0.2 vs. 1.6, p = 0.035) reflecting changes seen in the whole group. Overall, patients exposed to sodium and propylene glycol levels above UK daily limits reduced by 78% and 83% respectively. Mean levels of branched chain amino acids, haemoglobin, and white cell count were unchanged. Two adverse drug reactions (pancytopenia, fatigue/appetite loss) resolved without GPB discontinuation. Patients/families preferred GPB for its lower volume, greater palatability and easier administration. GPB appeared to improve biochemical measures and clinical outcomes. The causes are multi‐factorial and are likely to include prolonged action of GPB and its good tolerability, even at higher doses, facilitating tighter control of ammonia. |
| first_indexed | 2024-03-12T01:56:32Z |
| format | Article |
| id | doaj.art-cb4630541705478ab681b28299176d20 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-03-12T01:56:32Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-cb4630541705478ab681b28299176d202023-09-08T04:48:16ZengWileyJIMD Reports2192-83122023-09-0164531732610.1002/jmd2.12386Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centreMildrid Yeo0Preeya Rehsi1Megan Dorman2Stephanie Grunewald3Julien Baruteau4Anupam Chakrapani5Emma Footitt6Helen Prunty7Melanie McSweeney8Department of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKDepartment of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UKAbstract In urea cycle disorders (UCDs) ammonia scavenger drugs, usually sodium‐based, have been the mainstay of treatment. Increasingly, glycerol phenylbutyrate (GPB, Ravicti®) is being used but scant real‐world data exist regarding clinical outcomes. A retrospective study of UCD patients initiated on or switched to GPB was performed at a UK centre. Data on population characteristics, treatment aspects, laboratory measurements, and clinical outcomes were collected before and after patients started GPB with a sub‐group analysis undertaken for patients with ≥12 months of data before and after starting GPB. UCDs included arginosuccinate synthetase deficiency (n = 8), arginosuccinate lyase deficiency (n = 6), ornithine carbamoyltransferase deficiency (n = 3), and carbamoyl phosphate synthetase 1 deficiency (n = 3). In the sub‐group analysis (n = 11), GPB resulted in lower plasma ammonia (31 vs. 41 μmol/L, p = 0.037), glutamine (670 vs. 838 μmol/L, p = 0.002), annualised hyperammonaemic episodes (0.2 vs. 1.9, p = 0.020), hospitalisations (0.5 vs. 2.2, p = 0.010), and hyperammonaemic episodes resulting in hospitalisation (0.2 vs. 1.6, p = 0.035) reflecting changes seen in the whole group. Overall, patients exposed to sodium and propylene glycol levels above UK daily limits reduced by 78% and 83% respectively. Mean levels of branched chain amino acids, haemoglobin, and white cell count were unchanged. Two adverse drug reactions (pancytopenia, fatigue/appetite loss) resolved without GPB discontinuation. Patients/families preferred GPB for its lower volume, greater palatability and easier administration. GPB appeared to improve biochemical measures and clinical outcomes. The causes are multi‐factorial and are likely to include prolonged action of GPB and its good tolerability, even at higher doses, facilitating tighter control of ammonia.https://doi.org/10.1002/jmd2.12386glycerol phenylbutyratehyperammonaemiaRavictisodium benzoatesodium phenylbutyrateurea cycle disorders |
| spellingShingle | Mildrid Yeo Preeya Rehsi Megan Dorman Stephanie Grunewald Julien Baruteau Anupam Chakrapani Emma Footitt Helen Prunty Melanie McSweeney Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre JIMD Reports glycerol phenylbutyrate hyperammonaemia Ravicti sodium benzoate sodium phenylbutyrate urea cycle disorders |
| title | Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre |
| title_full | Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre |
| title_fullStr | Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre |
| title_full_unstemmed | Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre |
| title_short | Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre |
| title_sort | clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a uk paediatric centre |
| topic | glycerol phenylbutyrate hyperammonaemia Ravicti sodium benzoate sodium phenylbutyrate urea cycle disorders |
| url | https://doi.org/10.1002/jmd2.12386 |
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