A Pharmacometrics Approach to Improve Dose Individualisation Methods of Biologicals in Patients with Chronic Inflammatory Diseases
In clinical drug development, “one dose fits all” is a key objective. However, variability in exposure and thus response is common and can result in suboptimal treatment of individual patients. To hit a predefined exposure target in each patient, “therapeutic drug monitoring” (TDM) is often implemented. TDM helps improving attainment of a desired exposure target by guiding individualised drug dosing based upon drug concentrations. “Population models” can be employed to further maximise the success of TDM. These models can be applied to predict what will happen in the future and dosing can be adapted accordingly. The dictum of “one dose fits all” has been shown problematic in patients with chronic inflammatory diseases receiving biological therapies. Particular pathophysiological conditions in these patients often result in underexposure, making it difficult to properly treat these patients using standard dosing. With data from clinical trials, the applicant will develop population (and physiologically-based) models to characterise the dose-exposure- response relationship and to investigate dose optimisation opportunities (incl. model-informed precision dosing), thereby aiming to improve outcomes of (1) patients with ulcerative colitis or Crohn’s disease receiving infliximab, ustekinumab or vedolizumab therapy. (2) patients with psoriasis receiving adalimumab or guselkumab therapy.
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