Translating therapeutic drug monitoring of biopharmaceuticals into individualised care of inflammatory bowel disease patients through pharmacometric modelling en farmaco-economic evaluation.

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD). Approximately 2.2 million patients suffer from these incurable disabling diseases in Europe. State-of-the-art anti-tumour necrosis factor (TNF) alpha treatment (e.g. infliximab, adalimumab) is increasingly used throughout the disease course to induce and maintain clinical remission in IBD patients. Notwithstanding these drugs are very efficacious; nearly 40% of the patients will lose clinical benefit after one year of treatment (secondary loss of response). This is attributed to suboptimal dosing and immunogenicity that causes patients to develop anti-drug antibodies. Anti-TNF treatment costs € 15-20.000 per patient per year; hence many tens of thousands of euro are lost annually by treating drug-tolerant patients and by treating patients suboptimal. This research proposal has four objectives: 1) To identify an optimal drug level window for anti-TNF treatment in IBD. 2) To evaluate a patient-tailored treatment scheme based on personal therapeutic drug monitoring in randomised controlled trials. 3) To conduct a pharmacoeconomic evaluation of individualised anti-TNF treatment. 4) To investigate underlying causes of immunogenicity. The goal is to tailor anti-TNF dosing to the needs of the patient through monitoring of individual therapeutic drug levels and thereby increase the efficacy, patient safety and costeffectiveness of the treatment.