Yeo Mildrid, Rehsi Preeya, Dorman Megan, Grunewald Stephanie, Baruteau Julien, Chakrapani Anupam, Footitt Emma, Prunty Helen, McSweeney Melanie
Department of Paediatric Inherited Metabolic Disease Great Ormond Street Hospital NHS Foundation Trust and Institute for Child Health London UK.
JIMD Rep. 2023 Jul 23;64(5):317-326. doi: 10.1002/jmd2.12386. eCollection 2023 Sep.
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 ( = 8), arginosuccinate lyase deficiency ( = 6), ornithine carbamoyltransferase deficiency ( = 3), and carbamoyl phosphate synthetase 1 deficiency ( = 3). In the sub-group analysis ( = 11), GPB resulted in lower plasma ammonia (31 vs. 41 μmol/L, = 0.037), glutamine (670 vs. 838 μmol/L, = 0.002), annualised hyperammonaemic episodes (0.2 vs. 1.9, = 0.020), hospitalisations (0.5 vs. 2.2, = 0.010), and hyperammonaemic episodes resulting in hospitalisation (0.2 vs. 1.6, = 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.
在尿素循环障碍（UCDs）中，氨清除剂药物（通常为钠盐类）一直是主要的治疗手段。越来越多的人开始使用甘油苯丁酯（GPB，商品名Ravicti®），但关于其临床疗效的实际数据却很少。英国一家中心对开始使用或改用GPB的UCD患者进行了一项回顾性研究。在患者开始使用GPB前后收集了关于人口统计学特征、治疗方面、实验室检测结果和临床结局的数据，并对开始使用GPB前后有≥12个月数据的患者进行了亚组分析。UCDs包括精氨酸琥珀酸合成酶缺乏症（n = 8）、精氨酸琥珀酸裂解酶缺乏症（n = 6）、鸟氨酸氨甲酰基转移酶缺乏症（n = 3）和氨甲酰磷酸合成酶1缺乏症（n = 3）。在亚组分析（n = 11）中，GPB使血浆氨水平降低（31 vs. 41 μmol/L，P = 0.037）、谷氨酰胺水平降低（670 vs. 838 μmol/L，P = 0.002）、年化高氨血症发作次数降低（0.2 vs. 1.9，P = 0.020）、住院次数降低（0.5 vs. 2.2，P = 0.010）以及因高氨血症发作导致的住院次数降低（0.2 vs. 1.6，P = 0.035），这反映了整个组中观察到的变化。总体而言，暴露于高于英国每日限量的钠和丙二醇水平的患者分别减少了78%和83%。支链氨基酸、血红蛋白和白细胞计数的平均水平没有变化。两例药物不良反应（全血细胞减少、疲劳/食欲减退）在未停用GPB的情况下得到缓解。患者/家属更喜欢GPB，因为其体积更小、口感更好且给药更方便。GPB似乎改善了生化指标和临床结局。其原因是多方面的，可能包括GPB的作用时间延长及其良好的耐受性，即使在较高剂量下也能促进对氨的更严格控制。
