The Assessment of the Treatment and Management Landscape of Phenylketonuria survey study: Findings from 19 clinics in the United States
Biochemical/Metabolic and Therapeutics
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Introduction:
Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism characterized by chronic elevations of blood phenylalanine (Phe). While dietary management was historically the standard of care, patients with PKU are often unable to achieve and sustain recommended blood Phe levels with this approach. In recent years, with the US approval of pegvaliase for the treatment of adults with PKU with blood Phe >600 µmol/L and increased awareness of the detrimental effects of elevated Phe levels in adolescence and adulthood, the treatment landscape has changed. The aim of the Assessment of the Treatment and management LAndScape of phenylketonuria (ATLAS) survey study was to evaluate contemporary PKU treatment and management practices, physician experience of patient adherence to PKU treatment plans, and use of quality of life (QoL) questionnaires and neurocognitive assessments among US clinics treating patients with PKU.
Methods:
A retrospective physician survey was conducted via an online questionnaire in which anonymized aggregated data were collected on patients with PKU who were routinely managed (≥1 clinic follow-up within last 3 years) between December 2022 and July 2024.
Results:
A total of 19 clinics in the US provided responses to the survey. Clinics had a median of 40 years’ experience in managing patients with PKU. All clinics followed 2014 ACMG guidelines, recommending a target blood Phe of 120-360 µmol/L for patients of all ages; recommended clinic visit frequency and recommended blood Phe measurement frequency varied by age. Quality of life and neurocognitive questionnaires were routinely administered at 2 (10.5%) and 3 (15.8%) clinics, respectively. Across participating clinics, 2388 patients were actively managed; 52.1% were female and 54.8% were ≥18 years of age. A total of 986 actively managed patients (41.3%) were treated with medical nutrition therapy (MNT), 781 (32.7%) with sapropterin + MNT, and 372 (15.6% overall, 26.4% of patients ≥18 years of age) with pegvaliase. Among actively managed patients with available data, the proportion of patients with blood Phe 120-360 µmol/L decreased with age, from 82.6% for patients aged 0-4 years, 69.9% for those aged 5-11 years, 56.2% for those aged 12-17 years, 41.2% for those aged 18-29 years, 37.4% for those aged 30-44 years, and 28.2% for those aged 45+ years. The proportion of patients with Phe >1200 µmol/L increased with age, from 0% in patients aged 0-4 years to 9.4% in those aged 45+ years. The proportion of patients with Phe <120 µmol/L ranged from 2.4% to 7.0% and was highest among patients aged 0-4, 30-44, and 45+ years.
Conclusion:
The results of the ATLAS study demonstrate a shift in the treatment landscape and patient achievement of target blood Phe levels in recent years. Comparison of the findings from ATLAS with those from a similar survey conducted in 2015 (Jurecki et al, 2017) show that while blood Phe levels have remained similar in patients under 12 years, achievement of blood Phe 120-360 µmol/L in adults and adolescents has increased (from 46% to 56%, 35% to 41%, and 25% to 34% in patients aged 12-17, 18-29, and 30+, respectively). Correspondingly, the proportion of adult patients with blood Phe levels >1200 µmol/L has declined (from 15% to 6.0% and 20% to 7.4% in patients aged 18-29 and 30+ years, respectively). The improvements in blood Phe levels in the adult PKU population may be, at least in part, explained by increased awareness of the need for lifelong treatment as well as the availability of pegvaliase in this age group.
Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism characterized by chronic elevations of blood phenylalanine (Phe). While dietary management was historically the standard of care, patients with PKU are often unable to achieve and sustain recommended blood Phe levels with this approach. In recent years, with the US approval of pegvaliase for the treatment of adults with PKU with blood Phe >600 µmol/L and increased awareness of the detrimental effects of elevated Phe levels in adolescence and adulthood, the treatment landscape has changed. The aim of the Assessment of the Treatment and management LAndScape of phenylketonuria (ATLAS) survey study was to evaluate contemporary PKU treatment and management practices, physician experience of patient adherence to PKU treatment plans, and use of quality of life (QoL) questionnaires and neurocognitive assessments among US clinics treating patients with PKU.
Methods:
A retrospective physician survey was conducted via an online questionnaire in which anonymized aggregated data were collected on patients with PKU who were routinely managed (≥1 clinic follow-up within last 3 years) between December 2022 and July 2024.
Results:
A total of 19 clinics in the US provided responses to the survey. Clinics had a median of 40 years’ experience in managing patients with PKU. All clinics followed 2014 ACMG guidelines, recommending a target blood Phe of 120-360 µmol/L for patients of all ages; recommended clinic visit frequency and recommended blood Phe measurement frequency varied by age. Quality of life and neurocognitive questionnaires were routinely administered at 2 (10.5%) and 3 (15.8%) clinics, respectively. Across participating clinics, 2388 patients were actively managed; 52.1% were female and 54.8% were ≥18 years of age. A total of 986 actively managed patients (41.3%) were treated with medical nutrition therapy (MNT), 781 (32.7%) with sapropterin + MNT, and 372 (15.6% overall, 26.4% of patients ≥18 years of age) with pegvaliase. Among actively managed patients with available data, the proportion of patients with blood Phe 120-360 µmol/L decreased with age, from 82.6% for patients aged 0-4 years, 69.9% for those aged 5-11 years, 56.2% for those aged 12-17 years, 41.2% for those aged 18-29 years, 37.4% for those aged 30-44 years, and 28.2% for those aged 45+ years. The proportion of patients with Phe >1200 µmol/L increased with age, from 0% in patients aged 0-4 years to 9.4% in those aged 45+ years. The proportion of patients with Phe <120 µmol/L ranged from 2.4% to 7.0% and was highest among patients aged 0-4, 30-44, and 45+ years.
Conclusion:
The results of the ATLAS study demonstrate a shift in the treatment landscape and patient achievement of target blood Phe levels in recent years. Comparison of the findings from ATLAS with those from a similar survey conducted in 2015 (Jurecki et al, 2017) show that while blood Phe levels have remained similar in patients under 12 years, achievement of blood Phe 120-360 µmol/L in adults and adolescents has increased (from 46% to 56%, 35% to 41%, and 25% to 34% in patients aged 12-17, 18-29, and 30+, respectively). Correspondingly, the proportion of adult patients with blood Phe levels >1200 µmol/L has declined (from 15% to 6.0% and 20% to 7.4% in patients aged 18-29 and 30+ years, respectively). The improvements in blood Phe levels in the adult PKU population may be, at least in part, explained by increased awareness of the need for lifelong treatment as well as the availability of pegvaliase in this age group.