Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria.
Mol Genet Metab
; 128(1-2): 92-101, 2019.
Article
em En
| MEDLINE
| ID: mdl-31439512
ABSTRACT
Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency, resulting in high blood and brain Phenylalanine (Phe) concentrations that can lead to impaired brain development and function. Standard treatment involves a Phe-restricted diet alone or in conjunction with sapropterin dihydrochloride in responsive patients. The Food and Drug Administration approved pegvaliase enzyme substitution therapy for adults with blood Phe >600⯵mol/L in the US. Recently, the European Commission also approved pegvaliase for treatment of PKU patients aged 16â¯years or older with blood Phe >600⯵mol/L. The analyses presented below were conducted to provide comparative evidence on long-term treatment effectiveness of pegvaliase versus standard of care in adults with PKU. Adult patients (≥18â¯years) with baseline blood Phe >600⯵mol/L who had enrolled in the pegvaliase phase 2 and phase 3 clinical trials were propensity score-matched to historical cohorts of patients treated with "sapropterin + diet" or with "diet alone". These cohorts were derived from the PKU Demographics, Outcome and Safety (PKUDOS) registry and compared for clinical outcomes including blood Phe concentration and natural intact protein intake after 1 and 2â¯years. Propensity scores were estimated using logistic regression with probability of treatment as outcome (i.e. pegvaliase, "sapropterin + diet", or "diet alone") and patient demographic and disease severity covariates as predictors. An additional analysis in adult PKU patients with baseline blood Phe ≤600⯵mol/L comparing non-matched patient groups "sapropterin + diet" to "diet alone" using PKUDOS registry data only was also conducted. The analyses in patients with baseline blood Phe >600⯵mol comparing pegvaliase with "sapropterin + diet" (Nâ¯=â¯64 matched pairs) showed lower mean blood Phe concentrations after 1 and 2â¯years with pegvaliase (505 and 427⯵mol/L) versus "sapropterin + diet" (807 and 891⯵mol/L); mean natural intact protein intake after 1 and 2â¯years was 49 and 57â¯g/day respectively with pegvaliase versus 23 and 28â¯g/day with "sapropterin + diet". The analysis comparing pegvaliase with "diet alone" (Nâ¯=â¯120 matched pairs) showed lower mean blood Phe at 1 and 2â¯years with pegvaliase (473 and 302⯵mol/L) versus "diet alone" (1022 and 965⯵mol/L); mean natural intact protein intake after 1 and 2â¯years was 47 and 57â¯g/day with pegvaliase and 27 and 22â¯g/day with "diet alone". Considerably more patients achieved blood Phe ≤600, ≤360, and ≤120⯵mol/L and reductions from baseline of ≥20%, ≥30%, and ≥50% in blood Phe after 1 and 2â¯years of pegvaliase versus standard treatments. The analysis in patients with baseline blood Phe ≤600⯵mol/L showed lower blood Phe after 1 and 2â¯years with "sapropterin + diet" (240 and 324⯵mol/L) versus "diet alone" (580 and 549⯵mol/L) and greater percentages of patients achieving blood Phe targets ≤600, ≤360, and ≤120⯵mol/L and reductions from baseline of ≥20%, ≥30%, and ≥50% in blood Phe. These results support pegvaliase as the more effective treatment option to lower Phe levels in adults with PKU who have difficulty keeping blood Phe ≤600⯵mol/L with "diet alone". For patients with blood Phe ≤600⯵mol/L, adding sapropterin to dietary management is an appropriate treatment option, for those responsive to the treatment.
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Base de dados:
MEDLINE
Assunto principal:
Fenilalanina Amônia-Liase
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Fenilcetonúrias
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Proteínas Recombinantes
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Padrão de Cuidado
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article