#1105 PAn-european Registry Addressing Difelikefalin in Goal-oriented Medical treatment for chronic kidney disease-associated pruritus (PARADIGM): study design and research goals

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) affects 40%–60% of patients with kidney failure undergoing hemodialysis (HD). This debilitating condition significantly impacts health-related quality of life (HRQoL) and is associated with poor sleep, depression, hospitalization, and increased mortality. Despite its high prevalence, CKD-aP remains under-recognized and inadequately treated, with limited therapeutic options. Difelikefalin (DFK), a selective kappa-opioid receptor agonist, was approved by the FDA 2021 and EMA in 2022 for CKD-aP treatment. Clinical trials have shown DFK reduces pruritus, improves HRQoL, and alleviates symptoms like sleep disturbances in dialysis patients. However, real-world data on DFK's effectiveness, safety, and healthcare resource utilization (HCRU) are limited, necessitating further investigation. The Pan-European Registry Addressing Difelikefalin in Goal-oriented Medical treatment for chronic kidney disease-associated pruritus (PARADIGM) study aims to fill this gap by collecting real-world data on the use of DFK in patients undergoing HD. PARADIGM aims to (i) characterize patients initiating DFK, (ii) examine treatment patterns, (iii) assess effectiveness, (iv) evaluate safety and tolerability, and (v) assess HCRU among HD patients taking DFK. Method PARADIGM is an investigator-initiated, observational treatment registry led by Arbor Research Collaborative for Health, an organization serving as the coordinating center for the Dialysis Outcomes and Practice Patterns Study (DOPPS). PARADIGM will collect data from at least 400 DFK initiators across HD facilities in France, Germany, Italy, Spain, and the United Kingdom. Adult patients initiating DFK for CKD-aP while receiving in-center HD are eligible. Data will be collected via medical records, patient-reported outcome (PRO) questionnaires, and facility questionnaires, using ArborLink, a web-based electronic data collection system. At baseline (prior to DFK initiation), and at months 1, 3, 6, and 12 after DFK initiation, data on DFK prescription, medications, dialysis characteristics, lab measurements, and hospitalizations will be collected via medical record review. At each of the aforementioned timepoints, patients will complete PRO questionnaires, which include validated instruments, to assess itch severity, sleep quality, fatigue, depression, life participation, fall risk, dialysis recovery, side effects/symptoms, and HCRU. In patients who continue DFK treatment beyond 12 months, data collection will continue in 6 months intervals. If DFK is discontinued, providers will report reasons for discontinuation, and patients will complete follow-up PRO questionnaires 2 weeks, 2 months, and 6 months after their last treatment. Annual facility questionnaires will track DFK uptake and prescribing practices at participating facilities. Results Results from PARADIGM are not yet available, as patient recruitment is expected to begin in Q2 2025. PRO questionnaires will assess changes in itch severity, sleep quality, fatigue, depression, and life participation. Safety and tolerability will be evaluated through adverse events (e.g. dizziness, somnolence) monitoring, while HCRU analysis will focus on hospitalizations, emergency department visits, missed dialysis sessions, and healthcare referrals. Conclusion The PARADIGM study will advance the clinical understanding of CKD-aP treatment and provide essential real-world data on the use of DFK in the management of this condition in HD patients. By evaluating treatment patterns, effectiveness, safety, and HCRU, the study will help optimize DFK's role in CKD-aP management. The findings will inform clinical practice guideline development, future clinical trials, regulatory decisions, and healthcare policy, ultimately improving patient outcomes and enhancing the quality of life for CKD-aP patients undergoing hemodialysis.