Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years

摘要

Abstract Introduction Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. Methods Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2months to 2years were switched to, or started, GPB. Retrospective data up to 12months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia ( Results 82% and 53% of patients completed 3 and 6months of therapy, respectively (mean 8.85months, range 6days–18.4months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10% of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. Conclusion GPB was safe and effective in UCD patients aged 2months to 2years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB. Highlights ? Little data exist on using nitrogen scavenging drugs in infant UCD patients. ? The efficacy and safety of glycerol phenylbutyrate in infants are presented. ? Targeted short and long term ammonia levels were reached in most patients. ? Hyperammonemic crises were reduced over the study period. ? Glycerol phenylbutyrate was safe and effective in infant UCD patients.