Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria

Nicola Longo¹, David Dimmock², Harvey Levy³, Krista Viau³, Heather Bausell⁴, Deborah A Bilder⁵, Barbara Burton⁶, Christel Gross⁷, Hope Northrup⁸, Fran Rohr⁹, Stephanie Sacharow³, Amarilis Sanchez-Valle¹⁰, Mary Stuy¹¹, Janet Thomas¹², Jerry Vockley¹³, Roberto Zori¹⁴, Cary O Harding¹⁵

Affiliations

¹ Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA. Nicola.Longo@hsc.utah.edu.
² Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
³ Division of Genetics and Genomics, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
⁴ Division of Clinical Nutrition & Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
⁵ Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Medical Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷ Department of Pediatrics, University of Florida, Gainesville, FL, USA.
⁸ Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹ Nutrition Center, Boston Children's Hospital, Boston, MA, USA.
¹⁰ Division of Genetics and Metabolism, University of South Florida, Tampa, FL, USA.
¹¹ Department of Medical and Molecular Genetics, IU School of Medicine, Indianapolis, IN, USA.
¹² Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine, Aurora, CO, USA.
¹³ Department of Pediatrics University of Pittsburgh School of Medicine, Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
¹⁴ Division of Genetics and Metabolism, University of Florida, Gainesville, FL, USA.
¹⁵ Departments of Molecular and Medical Genetics and Pediatrics, Oregon Health & Science University, Portland, OR, USA.

PMID: 30546086
PMCID: PMC6752676
DOI: 10.1038/s41436-018-0403-z

Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria

Nicola Longo et al. Genet Med. 2019 Aug.

. 2019 Aug;21(8):1851-1867.

doi: 10.1038/s41436-018-0403-z. Epub 2018 Dec 14.

Authors

Affiliations

¹ Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA. Nicola.Longo@hsc.utah.edu.
² Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
³ Division of Genetics and Genomics, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
⁴ Division of Clinical Nutrition & Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
⁵ Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Medical Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷ Department of Pediatrics, University of Florida, Gainesville, FL, USA.
⁸ Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹ Nutrition Center, Boston Children's Hospital, Boston, MA, USA.
¹⁰ Division of Genetics and Metabolism, University of South Florida, Tampa, FL, USA.
¹¹ Department of Medical and Molecular Genetics, IU School of Medicine, Indianapolis, IN, USA.
¹² Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine, Aurora, CO, USA.
¹³ Department of Pediatrics University of Pittsburgh School of Medicine, Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
¹⁴ Division of Genetics and Metabolism, University of Florida, Gainesville, FL, USA.
¹⁵ Departments of Molecular and Medical Genetics and Pediatrics, Oregon Health & Science University, Portland, OR, USA.

PMID: 30546086
PMCID: PMC6752676
DOI: 10.1038/s41436-018-0403-z

Abstract

Purpose: Phenylketonuria (PKU) is a rare metabolic disorder that requires life-long management to reduce phenylalanine (Phe) concentrations within the recommended range. The availability of pegvaliase (PALYNZIQ™, an enzyme that can metabolize Phe) as a new therapy necessitates the provision of guidance for its use.

Methods: A Steering Committee comprising 17 health-care professionals with experience in using pegvaliase through the clinical development program drafted guidance statements during a series of face-to-face meetings. A modified Delphi methodology was used to demonstrate consensus among a wider group of health-care professionals with experience in using pegvaliase.

Results: Guidance statements were developed for four categories: (1) treatment goals and considerations prior to initiating therapy, (2) dosing considerations, (3) considerations for dietary management, and (4) best approaches to optimize medical management. A total of 34 guidance statements were included in the modified Delphi voting and consensus was reached on all after two rounds of voting.

Conclusion: Here we describe evidence- and consensus-based recommendations for the use of pegvaliase in adults with PKU. The manuscript was evaluated against the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and is intended for use by health-care professionals who will prescribe pegvaliase and those who will treat patients receiving pegvaliase.

Keywords: PALYNZIQ, pegvaliase; anaphylaxis management; dietary management; hypophenylalaninemia.

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Figures

**Fig. 1**
**Diet and dose-adjustment algorithm.** *DRI* dietary reference intake, *Phe* phenylalanine, *Tyr* tyrosine.

See this image and copyright information in PMC

References

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1. ten Hoedt AE, de Sonneville LM, Francois B, et al. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial. J Inherit Metab Dis. 2011;34:165–171. - PMC - PubMed
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Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria

Affiliations

Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding