Short summary

Patients will be randomized to either control group (treated as the physician deems best) or intervention group (treated per PK-model to maintain target levels). Blood and stool samples will be collected every 4 weeks, along with a brief questionnaire. Control group data will be blinded to physicians. Drug administrations will be registered. Clinic visits occur at weeks 0, 24, and 48. At week 48, disease activity will be assessed via endoscopy or imaging depending on disease placement.

Rationale

Biologic therapies, such as vedolizumab (VDZ) and ustekinumab (UST), offer effective treatment options for inflammatory bowel disease (IBD). 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 to symptom-based management.

Description of the cohort

Included patients must be ≥ 18 years of age, been diagnosed with ulcerative colitis or Crohn's disease. Patients must have received stable treatment with Vedolizumab or Ustekinumab of at least 3 months and must have had stable clinical disease activity for the same period of time with f-calprotectin ≤ 250 and a PRO2 of < 14 (weighted) for CD or ≤ 3 for UC (RB>1 is not allowed). Patients cannot be included if they have a pouch or a stoma. Neither can they be included if the primary reason for biologic treatment is fistulizing disease, if there is an expected eminent change of therapy, expected need for surgical intervention within the coming 3 months, as well as contraindication against continuing treatment with VDZ or UST, including prior acute or delayed infusion reaction to VDZ or UST, any active infection requiring parenteral treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus. Pregnant or nursing patients will not be included.

Data and biological material

At baseline we will collect demographic data. We will collect blood- and stool samples every 4 weeks. In a sub-protocol approximately 20 patients will have taken biopsies at baseline and end of study. The patients will also be asked to answer different questionnaires with different frequencies. Data from national registries will be used to assess sick-leave, early retirement etc.

Collaborating researchers and departments

Department of Medical Gastrointestinal Diseases, Odense University Hospital, Odense, Denmark

• Professor, MD, PhD, DMSc, Mark Andrew Ainsworth
• Professor, MD, PhD, Jens Kjeldsen
• Professor, MD, PhD, Casper Steenholdt

Department of Clinical Pharmacy and Biochemistry, Freie Universität Berlin, Berlin, Germany

• Prof. Dr. rer. nat. habil. Charlotte Kloft
• MSc Pharmacy, Ella Widigson

Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark

• MD, PhD, Lone Larsen

Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark

• Professor, MD, PhD, DMSc, Johan Burisch

Department of Internal Medicine, Section of Gastroenterology, Sygehus Lillebælt, Vejle, Denmark

• MD, PhD, Maiken Thyregod Jørgensen

Department of Internal Medicine, Section of Gastroenterology, Sydvestjysk Sygehus, Esbjerg, Denmark

• MD, PhD, Morten Lee Halling

Department of Internal Medicine, Section of Gastroenterology, Odense University Hospital, Svendborg, Denmark

• MD, Camilla Höglund

Department of Clinical Biochemistry, Odense University Hospital, Svendborg, Denmark

• MSc Biochemistry, PhD, Morten Beck Trelle

Centre for Evidence-Based Medicine Odense (CEBMO), University of Southern Denmark, Odense, Denmark

• Professor, MD, PhD, Asbjørn Hróbjartsson