Use of anti-TNF drug levels to optimise patient management.

Abstract

Anti-tumour necrosis factor (TNF) therapies, such as infliximab, adalimumab, certolizumab pegol and golimumab, have been proven to be effective for the treatment of patients with Crohn's disease and ulcerative colitis. However, 10%-30% of patients with inflammatory bowel disease (IBD) show no initial clinical benefit to anti-TNF therapy (primary non-response), and over 50% after an initial favourable outcome will lose response over time (secondary loss of response (SLR)). Numerous recent studies in IBD have revealed an exposure-response relationship suggesting a positive correlation between high serum anti-TNF concentrations and favourable therapeutic outcomes including clinical, biomarker and endoscopic remission, whereas antidrug antibodies have been associated with SLR and infusion reactions. Currently, therapeutic drug monitoring (TDM) is typically performed when treatment failure occurs either for SLR, drug intolerance (potential immune-mediated reaction) or infusion reaction (reactive TDM). Nevertheless, recent data demonstrate that proactive TDM and a treat-to-target (trough) therapeutic approach may more effectively optimise anti-TNF therapy efficacy, safety and cost. However, implementing TDM in real-life clinical practice is currently limited by the diversity in study design, therapeutic outcomes and assays used, which have hindered the identification of robust clinically relevant concentration thresholds. This review will focus mainly on the pharmacodynamic properties of anti-TNF therapy and the role of TDM in guiding therapeutic decisions in IBD.