PurposePhenylketonuria (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.MethodsA 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.ResultsGuidance 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.ConclusionHere 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.
Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. Until recently, the only treatment for PKU was a Phe-restricted diet. Increasing evidence of suboptimal outcomes in diet-treated individuals, inconsistent PKU management practices, and the recent availability of tetrahydrobiopterin (BH(4)) therapy have fueled the need for new management and treatment recommendations for this metabolic disorder. BH(4), now available as sapropterin dihydrochloride (sapropterin), may offer the potential for improved metabolic control as well as enhanced dietary Phe tolerance in some PKU patients. A group of metabolic dietitians from North America convened in June 2011 to draft recommendations for the use of sapropterin therapy in PKU. Physicians with extensive experience in PKU management were invited at a later date to contribute to the development of these recommendations. Based on extensive clinical experience and current evidence, the present recommendations provide guidance from patient selection and determination of sapropterin response to the long-term management of patients on sapropterin therapy. Target Phe levels, nutritional adequacy, neurocognitive screening and adherence to treatment are addressed to optimize patient outcomes.
Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.
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