Efficacy and safety of sapropterin before and during pregnancy: Final analysis of the Kuvan® Adult Maternal Paediatric European Registry (KAMPER) maternal and Phenylketonuria Developmental Outcomes and Safety (PKUDOS) PKU-MOMs sub-registries

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
François Feillet, Can Ficicioglu, Florian B. Lagler, Nicola Longo, Ania C. Muntau, Alberto Burlina, Friedrich K. Trefz, Francjan J. van Spronsen, Jean-Baptiste Arnoux, Kristin Lindstrom, Joshua Lilienstein, Gillian E. Clague, Richard Rowell, Barbara K. Burton, the KAMPER and PKUDOS investigators
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引用次数: 0

Abstract

Infants born to mothers with phenylketonuria (PKU) may develop congenital abnormalities because of elevated phenylalanine (Phe) levels in the mother during pregnancy. Maintenance of blood Phe levels between 120 and 360 μmol/L reduces risks of birth defects. Sapropterin dihydrochloride helps maintain blood Phe control, but there is limited evidence on its risk–benefit ratio when used during pregnancy. Data from the maternal sub-registries—KAMPER (NCT01016392) and PKUDOS (NCT00778206; PKU-MOMs sub-registry)—were collected to assess the long-term safety and efficacy of sapropterin in pregnant women in a real-life setting. Pregnancy and infant outcomes, and the safety of sapropterin were assessed. Final data from 79 pregnancies in 57 women with PKU are reported. Sapropterin dose was fairly constant before and during pregnancy, with blood Phe levels maintained in the recommended target range during the majority (82%) of pregnancies. Most pregnancies were carried to term, and the majority of liveborn infants were reported as ‘normal’ at birth. Few adverse and serious adverse events were considered related to sapropterin, with these occurring in participants with high blood Phe levels. This report represents the largest population of pregnant women with PKU exposed to sapropterin. Results demonstrate that exposure to sapropterin during pregnancy was well-tolerated and facilitated maintenance of blood Phe levels within the target range, resulting in normal delivery. This critical real-world data may facilitate physicians and patients to make informed treatment decisions about using sapropterin in pregnant women with PKU and in women of childbearing age with PKU who are responsive to sapropterin.

Abstract Image

怀孕前和怀孕期间沙普特林的疗效和安全性:欧洲库万®成人孕产妇儿科登记(KAMPER)孕产妇子登记和苯丙酮尿症发育结果与安全性(PKUDOS)PKU-MOMs 子登记的最终分析。
患有苯丙酮尿症(PKU)的母亲所生的婴儿可能会出现先天性畸形,因为母亲在怀孕期间体内的苯丙氨酸(Phe)水平升高。将血液中的 Phe 含量维持在 120 至 360 μmol/L 之间可降低出生缺陷的风险。盐酸沙泊三嗪有助于维持血 Phe 的控制,但关于其在孕期使用时的风险效益比的证据有限。我们收集了来自孕产妇子登记处--KAMPER(NCT01016392)和PKUDOS(NCT00778206;PKU-MOMs 子登记处)的数据,以评估在现实生活中孕妇使用沙普特林的长期安全性和有效性。对妊娠和婴儿结局以及沙普特林的安全性进行了评估。本文报告了 57 名患有 PKU 的孕妇 79 次妊娠的最终数据。怀孕前和怀孕期间,沙普特林的剂量相当稳定,大多数孕妇(82%)的血 Phe 水平保持在推荐的目标范围内。大多数孕妇都顺利分娩,据报告,大多数活产婴儿出生时 "正常"。与沙普特林有关的不良和严重不良事件极少,这些不良事件发生在血 Phe 水平较高的参试者中。这份报告代表了接触过沙普特林的最大一批 PKU 孕妇。结果表明,孕妇在怀孕期间接触沙普特林的耐受性良好,并有助于将血 Phe 水平维持在目标范围内,从而实现正常分娩。这一重要的真实世界数据有助于医生和患者做出明智的治疗决定,为患有 PKU 的孕妇以及对沙普特林有反应的患有 PKU 的育龄妇女使用沙普特林。
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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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