Efficacy and safety of sapropterin before and during pregnancy

TY - JOUR

T1 - Efficacy and safety of sapropterin before and during pregnancy

T2 - Final analysis of the Kuvan® Adult Maternal Paediatric European Registry (KAMPER) maternal and Phenylketonuria Developmental Outcomes and Safety (PKUDOS) PKU-MOMs sub-registries

AU - Feillet, François

AU - Ficicioglu, Can

AU - Lagler, Florian B

AU - Longo, Nicola

AU - Muntau, Ania C

AU - Burlina, Alberto

AU - Trefz, Friedrich K

AU - van Spronsen, Francjan J

AU - Arnoux, Jean-Baptiste

AU - Lindstrom, Kristin

AU - Lilienstein, Joshua

AU - Clague, Gillian E

AU - Rowell, Richard

AU - Burton, Barbara K

AU - KAMPER and PKUDOS investigators

N1 - © 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

PY - 2024/7

Y1 - 2024/7

N2 - 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.

AB - 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.

KW - Humans

KW - Pregnancy

KW - Female

KW - Registries

KW - Adult

KW - Phenylalanine/blood

KW - Biopterins/analogs & derivatives

KW - Infant, Newborn

KW - Phenylketonurias/drug therapy

KW - Pregnancy Outcome

KW - Phenylketonuria, Maternal/drug therapy

KW - Young Adult

KW - Europe

KW - Pregnancy Complications/drug therapy

U2 - 10.1002/jimd.12724

DO - 10.1002/jimd.12724

M3 - SCORING: Journal article

C2 - 38433424

VL - 47

SP - 636

EP - 650

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

IS - 4

ER -