Comment on "Pancreatic Enzyme Replacement Therapy in Pancreatic Exocrine Insufficiency-Real-World's Dosing and Effectiveness: A Systematic Review".

Pancreatic enzyme replacement therapy (PERT) is vital for managing pancreatic exocrine insufficiency (PEI), yet real-world use often deviates from guideline-recommended dosing. In response to the recent review by Kadaj-Lipka et al., we highlight several overlooked but critical factors influencing PERT effectiveness. While the review identifies underdosing trends, it does not address patient adherence or the timing of enzyme intake, both essential for therapeutic success. Clinical applicability was further limited by the inconsistent measurement of important nutritional outcomes like weight gain, fat absorption, and fat-soluble vitamin levels. Even though dosing requirements differ by cause, the review does not stratify findings by PEI etiology. Cost implications and high-dose safety concerns, particularly in pediatric or long-term use, were also not thoroughly investigated. We commend the authors' contribution but emphasize the importance of incorporating adherence, standardized outcomes, etiology-specific dosing, safety, and cost-effectiveness in future analyses to improve PERT delivery and patient outcomes.