Management of pegvaliase-related skin concerns: best practice recommendations using a modified Delphi approach

The approval of pegvaliase (PALYNZIQ®) represented a paradigm shift in the management of phenylketonuria (PKU) by enabling sustained reductions in blood phenylalanine levels and permitting an unrestricted diet. However, as it is a bacterially derived injectable therapy, individuals receiving pegvaliase may experience skin-related adverse events (AEs). Anticipating these AEs and other pegvaliase-related skin concerns and having best-practice strategies to manage them may be crucial to achieving optimal patient outcomes.

An expert panel comprising eight clinicians from the USA and Europe convened to develop best practice recommendations for managing pegvaliase-associated skin concerns. Employing a modified Delphi process, the panel generated 39 initial statements based on their clinical insights and results of a targeted literature review. These statements were refined over two phases of anonymous voting using a 10-point scale, with consensus predefined as ≥75% of panellists rating a statement ≥7.

The Delphi process resulted in 18 consensus statements. These were organized into three themes: patient-centric recommendations/considerations; considerations for premedications and concomitant medications; and recommendations for monitoring. Key recommendations included comprehensive patient education to overcome needle phobia and promote self-injection; training on injection technique and rotation to reduce scar tissue formation; and the proactive use of premedications and as-needed concomitant medications to mitigate skin reactions. Recommendations also emphasize the importance of regular in-person follow-up to assess injection sites and monitor for scar tissue. Mean agreement scores ranged from 8.5 to 10, reflecting robust consensus among panel members.

These internationally relevant, evidence-based recommendations provide a structured framework for managing pegvaliase-related skin concerns. Adoption of this guidance may enhance treatment adherence, mitigate adverse events, and ultimately improve patient outcomes.