Disease Burden and Pharmacological Treatment Patterns in Children and Adults With Phenylketonuria: A Real‐World Matched Cohort Study

Phenylketonuria (PKU) is caused by defective catabolism of phenylalanine (Phe), resulting in Phe accumulation and subsequent neurocognitive impairment. This retrospective study used a large United States claims database linked to laboratory records (6/2018-05/2023) to compare comorbidities, healthcare resource utilization, and healthcare costs between individuals with PKU and matched controls, stratified by age and Phe level, as well as describe pharmacological treatment patterns among individuals with PKU. The study included 5729 and 2648 matched pairs aged ≥ 12 and < 12 years, respectively (mean age: 31 and 3 years; 60% and 47% female). Individuals aged ≥ 12 years with PKU had significantly higher prevalence of neuropsychiatric and cognitive comorbidities than controls, including intellectual or developmental disabilities (prevalence difference: 5.2%), fatigue and malaise (4.9%), and anxiety (4.2%; all p < 0.05), along with other comorbidities across multiple organ systems. Individuals aged ≥ 12 years with PKU also accessed the healthcare system more than controls (39% more hospitalizations, 18% more emergency room visits, and 25% more outpatient visits) and incurred higher medical and pharmacy costs ($2869 and $9075, respectively; p < 0.05). Individuals aged < 12 years similarly had higher burden than controls, but only for certain outcomes and at smaller magnitudes. Individuals with Phe ≥ 600 μmol/L showed a greater incremental burden for certain comorbidities, such as intellectual or developmental disabilities, compared to individuals with Phe < 600 μmol/L. These findings demonstrate the substantial burden of PKU across age and Phe level strata, notably in those aged ≥ 12 years, highlighting the need for improved treatments.