Long-term safety of sapropterin in paediatric and adult individuals with phenylalanine hydroxylase deficiency: Final results of the Kuvan® Adult Maternal Paediatric European Registry multinational observational study.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
François Feillet, Jean-Baptiste Arnoux, María Bueno Delgado, Alberto Burlina, Brigitte Chabrol, Ece Kucuksayrac, Florian B Lagler, Ania C Muntau, David Olsson, Sabrina Paci, Frank Rutsch, Francjan J van Spronsen
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引用次数: 0

Abstract

Phenylketonuria is a rare inherited disorder that disrupts the metabolism of phenylalanine (Phe) to tyrosine by phenylalanine hydroxylase (PAH). Sapropterin dihydrochloride (Kuvan®) is approved for use in Europe to reduce blood Phe levels and improve Phe tolerance in sapropterin-responsive individuals. KAMPER (NCT01016392) is an observational, multinational registry assessing long-term safety and efficacy of sapropterin. Five hundred and seventy-six participants with PAH deficiency were enrolled from nine European countries (69 sites; December 2009-May 2016). Participants were aged <4 years (n = 11), 4 to <12 years (n = 329), 12 to <18 years (n = 141), and ≥18 years (n = 95) at enrolment. Overall, 401 (69.6%) participants experienced a total of 1960 adverse events; 61 events in 42 participants were serious, and two were considered sapropterin-related by the investigator. Mean (standard deviation) actual dietary Phe intake increased from baseline across all age groups: 957 (799) mg/day to a maximum of 1959 (1121) mg/day over a total study period of 11 years. Most participants exhibited an increase in Phe tolerance while blood Phe levels remained in the target range for their age (120-360 μmol/L for <12 years; 120-600 μmol/L for ≥12 years). Most participants exhibited normal growth for height, weight, and body mass index. No additional safety concerns were identified. As an observational study, limitations include variability in routine care practices and inconsistent availability of data. Long-term sapropterin use demonstrates a favourable safety profile in real-world settings and increases Phe tolerance in participants with PAH deficiency while maintaining blood Phe levels in the target ranges.

苯丙氨酸羟化酶缺乏症患儿和成人服用沙普特林的长期安全性:Kuvan®(库万®)成人孕产妇儿科欧洲注册多国观察研究的最终结果。
苯丙酮尿症是一种罕见的遗传性疾病,它会破坏苯丙氨酸羟化酶(PAH)将苯丙氨酸(Phe)代谢为酪氨酸的过程。欧洲已批准使用盐酸沙普特林(Kuvan®)来降低血液中的 Phe 水平,并改善对沙普特林有反应的人对 Phe 的耐受性。KAMPER(NCT01016392)是一项观察性多国登记项目,旨在评估沙普特林的长期安全性和有效性。来自 9 个欧洲国家(69 个研究机构;2009 年 12 月至 2016 年 5 月)的 576 名 PAH 缺乏症患者接受了登记。参与者年龄为
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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