Aetiology-Specific Pancreatic Enzyme Dose Requirements and Treatment Outcomes in Pancreatic Exocrine Insufficiency: The Multicentre EURO-PEI Registry.

BACKGROUND Pancreatic exocrine insufficiency (PEI) is a maldigestion syndrome leading to symptoms and nutritional deficiencies. Prospective real-world data on pancreatic enzyme replacement therapy (PERT) dose requirements across aetiologies are limited. OBJECTIVE To define PERT dose requirements and treatment outcomes across PEI aetiologies in specialist European practice. METHODS EURO-PEI was a multicentre observational registry with predominantly prospective data collection conducted at eight pancreatic centres in five European countries between June 2021 and September 2025. Adults with clinician-established PEI in whom PERT was initiated or actively optimised were included. The primary outcome was the optimised PERT dose associated with the achievement of a clinician-assessed therapeutic goal: improvement or resolution of PEI-related symptoms with normalisation or clinically relevant improvement of nutritional abnormalities. RESULTS Among 1015 patients, PEI was secondary to chronic pancreatitis in 496 (48.9%), pancreatectomy in 185 (18.2%), pancreatic cancer in 174 (17.1%), and acute pancreatitis in 95 (9.4%). Median total daily optimised doses were highest after pancreatectomy (240,000 PhU, IQR 175,000-375,000) and in pancreatic cancer (210,000 PhU, 175,000-325,000), compared with chronic pancreatitis (175,000 PhU, 120,000-210,000) and acute pancreatitis (100,000 PhU, 75,000-200,000). After optimisation, the therapeutic goal was achieved in 951 patients (93.7%); of these, 446 (46.9%) required enzyme doses exceeding commonly recommended starting doses. Related adverse events occurred in 38 patients (3.7%). CONCLUSIONS PERT dose requirements vary substantially by PEI aetiology, supporting aetiology-aware starting doses, early reassessment, and individualised optimisation in high-risk groups.