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Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre

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 sw...

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Autores principales: Yeo, Mildrid, Rehsi, Preeya, Dorman, Megan, Grunewald, Stephanie, Baruteau, Julien, Chakrapani, Anupam, Footitt, Emma, Prunty, Helen, McSweeney, Melanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494499/
https://www.ncbi.nlm.nih.gov/pubmed/37701329
http://dx.doi.org/10.1002/jmd2.12386
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author Yeo, Mildrid
Rehsi, Preeya
Dorman, Megan
Grunewald, Stephanie
Baruteau, Julien
Chakrapani, Anupam
Footitt, Emma
Prunty, Helen
McSweeney, Melanie
author_facet Yeo, Mildrid
Rehsi, Preeya
Dorman, Megan
Grunewald, Stephanie
Baruteau, Julien
Chakrapani, Anupam
Footitt, Emma
Prunty, Helen
McSweeney, Melanie
author_sort Yeo, Mildrid
collection PubMed
description 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.
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spelling pubmed-104944992023-09-12 Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre Yeo, Mildrid Rehsi, Preeya Dorman, Megan Grunewald, Stephanie Baruteau, Julien Chakrapani, Anupam Footitt, Emma Prunty, Helen McSweeney, Melanie JIMD Rep Case Reports 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. John Wiley & Sons, Inc. 2023-07-23 /pmc/articles/PMC10494499/ /pubmed/37701329 http://dx.doi.org/10.1002/jmd2.12386 Text en © 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Reports
Yeo, Mildrid
Rehsi, Preeya
Dorman, Megan
Grunewald, Stephanie
Baruteau, Julien
Chakrapani, Anupam
Footitt, Emma
Prunty, Helen
McSweeney, Melanie
Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre
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 Case Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494499/
https://www.ncbi.nlm.nih.gov/pubmed/37701329
http://dx.doi.org/10.1002/jmd2.12386
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