Abstract Background Biologic therapies, including vedolizumab (VDZ) and ustekinumab (UST), provide effective treatment options for inflammatory bowel disease (IBD). Although evidence is limited, clinicians often escalate the dosing regimen when clinical symptoms or biomarkers suggest a waning effect or loss of response. This study aims to assess whether Model-Informed Precision Dosing (MIPD) can match the efficacy of conventional symptom-based management while providing superior cost-effectiveness. Methods This prospective, unblinded randomized controlled trial will be conducted at seven Danish centers and enroll 166 patients with Crohn’s disease or ulcerative colitis who have been on stable VDZ or UST therapy for at least three months. Exclusion criteria include a diagnosis of IBD unclassified, as well as having a pouch or stoma, and fistulizing disease being the primary reason for treatment with biologics. Participants will continue treatment with the biologic they were receiving prior to enrollment and will be randomized to either standard symptom- and biomarker-based dosing or dosing guided by therapeutic drug monitoring using pharmacokinetic (PK) models and PK/pharmacodynamic (PKPD) targets (MIPD). Laboratory results obtained every four weeks (±1 week) will be incorporated into the PK model, which will be used to predict whether adjustments to dosing frequency are warranted. Results The primary outcome is steroid-free remission at week 48. Secondary outcomes include mucosal healing at week 48, clinical remission determined based on both patient-reported symptom measures and clinician-rated disease activity, as fraction of observation period and at week 48 respectively. Further, biochemical remission, PK measures, and cost-effectiveness encompassing secondary outcomes. Recruitment is planned for late 2025, with results expected in 2028. Conclusion The trial has been approved by the Danish Medicines Agency and The Medical Research Ethics Committee. Results will be published in peer-reviewed journals and presented at international conferences. The study is registered under EU CT number: 2024-517123-39-00 and https://clinicaltrials.gov/study/NCT06788340. Conflict of interest: Mrs. Frimor, Camilla: Steenholdt, Casper: No conflict of interest Widigson, Ella: No conflict of interest Larsen, Lone: Speaker fee from Takeda, and has served as an advisory board member for Tillots and AbbVie Burisch, Johan: grants from AbbVie,Janssen-Cilag, MSD, Takeda, Tillots Pharma, Bistrol Myers Squibb and Novo Nordisk Foundation personal fees from AbbVie, Janssen-Cilag, Celgene, MSD, Pfizer, Takeda, Tillots Pharma, Bistrol Myers Squibb, Samsung Bioepis, Pharmacosmos, Ferring, Galapagos, Eli Lilly, Dr Falk Pharma and Orion Pharma. Jørgensen, Maiken Thyregod: No conflict of interest Halling, Morten: Personal fee from TAKEDA Kloft, Charlotte: grant from an industry consortium (AbbVie. Astra Zeneca, Boehringer Ingelheim, F. Hoffmann-La Roche, Merck, Novo Nordisk and Sanofi) for the PharMetrX PhD program and from the European Commission within the Horizon 2020 framework program (“FAIR”) Ainsworth, Mark Andrew: lectures/consulting for Abbvie, Celltrion, Eli Lilly, Janssen, MSD
Frimor et al. (Thu,) studied this question.