Maiken Thyregod Joergensen

Background and aims: No medications are currently approved for the prevention of recurrent acute pancreatitis. This trial evaluated whether naldemedine, a peripherally acting μ ‐opioid receptor antagonist, reduces the risk of acute pancreatitis in patients with recurrent acute pancreatitis. Methods: This was a multicentre, double‐blinded, placebo‐controlled randomised trial conducted at four Danish pancreatitis referral centres. Participants aged 18–75 years with recurrent acute pancreatitis, both with and without a diagnosis of chronic pancreatitis, were randomised to receive naldemedine 0.2 mg or a matching placebo daily for up to 12 months. The primary outcome was acute pancreatitis recurrence, defined by the revised Atlanta Criteria. Secondary outcomes included pain flares, gastrointestinal symptoms, and quality of life. At the end of follow‐up, the participant's global impression of change, safety and tolerability outcomes, new‐onset diabetes and pancreatic exocrine insufficiency were assessed. Results: 74 participants (mean age: 46 years; 41% female) were randomised to naldemedine ( n = 36) or placebo ( n = 38). During a median follow‐up time of 365 days (IQR, 352–370), participants in the naldemedine group had a numerically lower risk of acute pancreatitis compared to placebo (HR 0.54; 95% CI, 0.29–1.01; p = 0.05). No differences were observed between the groups for secondary efficacy, safety, and tolerability outcomes. Participants treated with naldemedine for at least 1 year had a lower risk of acute pancreatitis (HR 0.49; 95% CI, 0.24–0.97; p = 0.04). Conclusions: Treatment with naldemedine was safe and well‐tolerated and may reduce the risk of recurrent acute pancreatitis. A larger confirmatory trial is needed to verify these findings. Trial registration: ClinicalTrials.gov Identifier: PAMORA‐RAP: NCT04966559

Introduction: Biologic therapies, such as vedolizumab (VDZ) and ustekinumab (UST), offer effective treatment options for inflammatory bowel disease. In spite of limited evidence, it is common practice to escalate the dosing regimen if clinical symptoms or biomarkers give suspicion of loss of response. This study aims to determine whether model-informed precision dosing (MIPD) can provide equal efficacy and possibly superior cost-effectiveness compared with symptom-based management. Methods and analysis: This study is an unblinded, randomised controlled trial, conducted at six centres in Denmark. A total of 166 patients diagnosed with Crohn’s disease or ulcerative colitis who have been on stable VDZ or UST therapy for at least 3 months will be enrolled. Participants will be randomised to receive either continued symptom and biomarker-based dosing (control group) or dosing guided by therapeutic drug monitor using pharmacokinetic (PK) models together with PK-pharmacodynamic targets (=MIPD; intervention group). The primary endpoint is the fraction of patients in steroid-free remission at the end of the observation period. Secondary endpoints include mucosal healing, clinical remission, biochemical disease control, PK assessment and cost-effectiveness. Ethics and dissemination: The trial has been approved by the Danish Medicines Agency and The Medical Research Ethics Committee. No study-related procedures will take place before patients have signed written informed consent. Results will be published in peer-reviewed journals and presented at international conferences. Trial registration numbers: EUCT, 2024-517123-39-00; NCT06788340 .