Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias
Abstract 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 (NH3) sca...
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0840-4 |
| _version_ | 1819150022768328704 |
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| author | Anupam Chakrapani Vassili Valayannopoulos Nuria García Segarra Mireia Del Toro Maria Alice Donati Angeles García-Cazorla María Julieta González Celine Plisson Vincenzo Giordano |
| author_facet | Anupam Chakrapani Vassili Valayannopoulos Nuria García Segarra Mireia Del Toro Maria Alice Donati Angeles García-Cazorla María Julieta González Celine Plisson Vincenzo Giordano |
| author_sort | Anupam Chakrapani |
| collection | DOAJ |
| description | Abstract 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 (NH3) scavengers compared with scavengers alone for reducing plasma NH3 levels in patients with OAs and hyperammonaemia (plasma NH3 > 60 μmol/L) during decompensation episodes. NH3 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 NH3 scavengers (22 patients) and 27 with carglumic acid combined with NH3 scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH3 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 NH3 scavenger group. Median baseline NH3 level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH3 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 NH3 levels were higher in the combination and carglumic acid groups, mean reduction in NH3 levels to 72 h in both groups was greater than the NH3 scavengers’ group; reductions were greatest in the combination group. Mean change in plasma NH3 vs baseline in the carglumic acid, NH3 scavengers and combination groups, respectively, was − 13, + 12% and − 27% at 0–12 h (p < 0.05 NH3 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 NH3 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 NH3 scavengers, the reduction in NH3 was greater than with NH3 scavengers alone in the first 72 h. |
| first_indexed | 2024-12-22T14:10:54Z |
| format | Article |
| id | doaj.art-29e9b5f3d6da47d29d22f5ccee2d9923 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T14:10:54Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-29e9b5f3d6da47d29d22f5ccee2d99232022-12-21T18:23:12ZengBMCOrphanet Journal of Rare Diseases1750-11722018-06-011311910.1186/s13023-018-0840-4Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic aciduriasAnupam Chakrapani0Vassili Valayannopoulos1Nuria García Segarra2Mireia Del Toro3Maria Alice Donati4Angeles García-Cazorla5María Julieta González6Celine Plisson7Vincenzo Giordano8Metabolic Medicine Department, Great Ormond Street Hospital NHS Foundation TrustHôpital Necker-Enfants MaladesReference Centre for Inherited Metabolic Diseases, Hôpital Robert DebréServicio de Neurologíia Infantil, Hospital Vall d’HebrónReference Centre for Inherited Metabolic and Muscular Disease, Azienda Ospedaliero Universitaria MeyerHospital Sant Joan de Déu and CIBERER, Instituto de Salud Carlos IIIHospital Sant Joan de Déu and CIBERER, Instituto de Salud Carlos IIIMedical Affairs, Orphan EuropeOrphan EuropeAbstract 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 (NH3) scavengers compared with scavengers alone for reducing plasma NH3 levels in patients with OAs and hyperammonaemia (plasma NH3 > 60 μmol/L) during decompensation episodes. NH3 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 NH3 scavengers (22 patients) and 27 with carglumic acid combined with NH3 scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH3 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 NH3 scavenger group. Median baseline NH3 level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH3 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 NH3 levels were higher in the combination and carglumic acid groups, mean reduction in NH3 levels to 72 h in both groups was greater than the NH3 scavengers’ group; reductions were greatest in the combination group. Mean change in plasma NH3 vs baseline in the carglumic acid, NH3 scavengers and combination groups, respectively, was − 13, + 12% and − 27% at 0–12 h (p < 0.05 NH3 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 NH3 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 NH3 scavengers, the reduction in NH3 was greater than with NH3 scavengers alone in the first 72 h.http://link.springer.com/article/10.1186/s13023-018-0840-4Carglumic acidAmmonia scavengersOrganic aciduriaHyperammonaemiaDecompensationExtracorporeal detoxification |
| spellingShingle | Anupam Chakrapani Vassili Valayannopoulos Nuria García Segarra Mireia Del Toro Maria Alice Donati Angeles García-Cazorla María Julieta González Celine Plisson Vincenzo Giordano Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias Orphanet Journal of Rare Diseases Carglumic acid Ammonia scavengers Organic aciduria Hyperammonaemia Decompensation Extracorporeal detoxification |
| 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 | Carglumic acid Ammonia scavengers Organic aciduria Hyperammonaemia Decompensation Extracorporeal detoxification |
| url | http://link.springer.com/article/10.1186/s13023-018-0840-4 |
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