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Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias
BACKGROUND: Hyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment. METHODS: A post-hoc analysis of two retrospective studies analysed the efficacy of carglumic acid ± ammonia (NH(3)) scavenge...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011521/ https://www.ncbi.nlm.nih.gov/pubmed/29925411 http://dx.doi.org/10.1186/s13023-018-0840-4 |
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author | Chakrapani, Anupam Valayannopoulos, Vassili Segarra, Nuria García Del Toro, Mireia Donati, Maria Alice García-Cazorla, Angeles González, María Julieta Plisson, Celine Giordano, Vincenzo |
author_facet | Chakrapani, Anupam Valayannopoulos, Vassili Segarra, Nuria García Del Toro, Mireia Donati, Maria Alice García-Cazorla, Angeles González, María Julieta Plisson, Celine Giordano, Vincenzo |
author_sort | Chakrapani, Anupam |
collection | PubMed |
description | BACKGROUND: Hyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment. METHODS: A post-hoc analysis of two retrospective studies analysed the efficacy of carglumic acid ± ammonia (NH(3)) scavengers compared with scavengers alone for reducing plasma NH(3) levels in patients with OAs and hyperammonaemia (plasma NH(3) > 60 μmol/L) during decompensation episodes. NH(3) was analysed in 12-h periods at 0–48 h and 24-h periods at 48–120 h. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Of 98 episodes, 38 were treated with carglumic acid (34 patients), 33 with NH(3) scavengers (22 patients) and 27 with carglumic acid combined with NH(3) scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH(3) scavengers group) and 74% (combination group) of episodes occurred in neonates. Median episode duration was 6 days for the carglumic acid and combination groups, and 9 days for the NH(3) scavenger group. Median baseline NH(3) level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH(3) scavengers; and 271 μmol/L, combination; 13, 30 and 11% of episodes required extracorporeal detoxification (ED), respectively. Data were censored at ED initiation. While baseline NH(3) levels were higher in the combination and carglumic acid groups, mean reduction in NH(3) levels to 72 h in both groups was greater than the NH(3) scavengers’ group; reductions were greatest in the combination group. Mean change in plasma NH(3) vs baseline in the carglumic acid, NH(3) scavengers and combination groups, respectively, was − 13, + 12% and − 27% at 0–12 h (p < 0.05 NH(3) scavengers vs combination); − 47, − 22% and − 52% at 12–24 h (not significant); − 44, − 5% and − 61% at 24–48 h; and − 66, − 16% and − 76% at 48–72 h (p < 0.05 carglumic acid/combination groups vs NH(3) scavengers for both timepoints). The number of TEAEs was similar between groups and mainly related to the disease/condition. CONCLUSIONS: Carglumic acid is a well-tolerated and efficacious treatment for OA decompensation episodes. When given alone or combined with NH(3) scavengers, the reduction in NH(3) was greater than with NH(3) scavengers alone in the first 72 h. |
format | Online Article Text |
id | pubmed-6011521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60115212018-07-05 Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias Chakrapani, Anupam Valayannopoulos, Vassili Segarra, Nuria García Del Toro, Mireia Donati, Maria Alice García-Cazorla, Angeles González, María Julieta Plisson, Celine Giordano, Vincenzo Orphanet J Rare Dis Research BACKGROUND: Hyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment. METHODS: A post-hoc analysis of two retrospective studies analysed the efficacy of carglumic acid ± ammonia (NH(3)) scavengers compared with scavengers alone for reducing plasma NH(3) levels in patients with OAs and hyperammonaemia (plasma NH(3) > 60 μmol/L) during decompensation episodes. NH(3) was analysed in 12-h periods at 0–48 h and 24-h periods at 48–120 h. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Of 98 episodes, 38 were treated with carglumic acid (34 patients), 33 with NH(3) scavengers (22 patients) and 27 with carglumic acid combined with NH(3) scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH(3) scavengers group) and 74% (combination group) of episodes occurred in neonates. Median episode duration was 6 days for the carglumic acid and combination groups, and 9 days for the NH(3) scavenger group. Median baseline NH(3) level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH(3) scavengers; and 271 μmol/L, combination; 13, 30 and 11% of episodes required extracorporeal detoxification (ED), respectively. Data were censored at ED initiation. While baseline NH(3) levels were higher in the combination and carglumic acid groups, mean reduction in NH(3) levels to 72 h in both groups was greater than the NH(3) scavengers’ group; reductions were greatest in the combination group. Mean change in plasma NH(3) vs baseline in the carglumic acid, NH(3) scavengers and combination groups, respectively, was − 13, + 12% and − 27% at 0–12 h (p < 0.05 NH(3) scavengers vs combination); − 47, − 22% and − 52% at 12–24 h (not significant); − 44, − 5% and − 61% at 24–48 h; and − 66, − 16% and − 76% at 48–72 h (p < 0.05 carglumic acid/combination groups vs NH(3) scavengers for both timepoints). The number of TEAEs was similar between groups and mainly related to the disease/condition. CONCLUSIONS: Carglumic acid is a well-tolerated and efficacious treatment for OA decompensation episodes. When given alone or combined with NH(3) scavengers, the reduction in NH(3) was greater than with NH(3) scavengers alone in the first 72 h. BioMed Central 2018-06-20 /pmc/articles/PMC6011521/ /pubmed/29925411 http://dx.doi.org/10.1186/s13023-018-0840-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chakrapani, Anupam Valayannopoulos, Vassili Segarra, Nuria García Del Toro, Mireia Donati, Maria Alice García-Cazorla, Angeles González, María Julieta Plisson, Celine Giordano, Vincenzo Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title | Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title_full | Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title_fullStr | Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title_full_unstemmed | Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title_short | Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
title_sort | effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011521/ https://www.ncbi.nlm.nih.gov/pubmed/29925411 http://dx.doi.org/10.1186/s13023-018-0840-4 |
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