摘要：Background Phenylketonuria (PKU) leads to an accumulation of phenylalanine (Phe) in the blood and subsequent neurologic, cognitive, psychiatric, and behavioral dysfunction. Many patients report social isolation and decreased quality of life. Pegvaliase is an enzyme substitution therapy that reduces blood Phe levels in patients with PKU and is associated with a risk of hypersensitivity reactions. Objective To define the minimum acceptable benefit (MAB) of pegvaliase, i.e., the minimum probability of achieving a blood Phe level <360 μmol/L, which patients require to tolerate the risks of hypersensitivity associated with pegvaliase. Methods Adult, pegvaliase-naïve patients with blood Phe levels >600 μmol/L participated in a patient-preference web survey using two surveys: adapted swing-weighting and thresholding. Participants were asked to make ordinal choices between varying clinical benefit and severity levels for hypersensitivity. Disease effects and treatment satisfaction were also assessed. Results Among 45 participants, the mean (standard deviation) self-reported blood Phe level was 976.9 (429.9) μmol/L; only 28.8% reported satisfaction with their current treatment. Most (84.4%) indicated difficulty in following a PKU diet; 60% reported that the PKU diet was burdensome, and 58% reported feeling socially isolated. Most (≥69%) reported their MAB to be less than the expected clinical benefit provided by pegvaliase; the mean MAB was 22.7% and 34.4% in the swing-weighting and thresholding surveys, respectively. Conclusion Most participants felt the burden of PKU on their daily lives, were dissatisfied with current treatments, and were willing to accept the risks of hypersensitivity reactions to achieve recommended blood Phe levels with pegvaliase treatment.
关键词：Phenylketonuria ; PKU ; Pegvaliase ; Minimum acceptable benefit ; Benefit-risk analysis ; Patient preference ; ANOVA analysis of variance ; FDA Food and Drug Administration ; IgE immunoglobin E ; MAB minimum acceptable benefit ; Phe phenylalanine ; PKU phenylketonuria ; SD standard deviation ; SE standard error
