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.

Autor: Feillet F; Hôpital d'enfants Brabois, Vandœuvre-lès-Nancy, France., Arnoux JB; Necker-Enfants Malades University Hospital, APHP, Paris, France., Delgado MB; Hospital Universitario Virgen del Rocío, Sevilla, Spain., Burlina A; University Hospital, Padova, Italy., Chabrol B; Timone Children's University Hospital, AP-HM, Marseille, France., Kucuksayrac E; BioMarin Europe Ltd., London, UK., Lagler FB; Paracelsus Medical University, Salzburg, Austria., Muntau AC; University Children's Hospital, Medical Center Hamburg-Eppendorf, Hamburg, Germany., Olsson D; Karolinska University Hospital, Stockholm, Sweden., Paci S; Pediatric Department, San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy., Rutsch F; Muenster University Children's Hospital, Muenster, Germany., van Spronsen FJ; Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2024 Sep 05. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1002/jimd.12796
Abstrakt: 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.
(© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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