Several recent publications have confirmed that knowing tumour necrosis factor-α (TNF-α) antagonist trough levels will result in different decisions that using clinical information alone(1), results in fewer flares(2), and is cost effective.(3) Using trough levels during secondary loss of response can guide therapy. In the presence of low trough levels and low antidrug antibody (ADA) levels, dose optimization can often restore clinical response, and although pharmacokinetic models suggest that shortening the dosing interval is superior to increasing the dose, there do not seem to be significant differences between the strategies clinically.(4)
Patients who do not benefit from dose optimization may respond to a switch to a second TNF-α antagonist, but efficacy tends to be lower than with the first agent. A radioimmunoassay study found infliximab levels between 3 and 10 μg/mL appear to be an appropriate trough therapeutic range. Patients with levels <3 μg/mL should have their dose escalated. In addition, infliximab ADA <10 ug/mL can be overcome with dose escalation. Levels >10 ug/mL are associated with a higher loss of response and infliximab infusion rate reactions, which can rarely be overcome with dose escalation.
An analysis of the association between trough drug levels and ADAs evaluated outcomes of interventions implemented in patients with loss of response to infliximab or adalimumab.(5) Patients with undetectable or low ADA titres responded to dose intensification. Patients with adequate trough levels (>4.5 μg/mL adalimumab and >3.8 μg/mL infliximab) did not respond to dose intensification or a switch to another TNF-α antagonist but did respond to expectant management or out-of-class interventions. Patients with >4 μg/mL-equivalent adalimumab ADA or >9 μg/mL-equivalent infliximab ADAs did not respond to an increased drug dosage but did respond to switching TNF-α antagonists. TDM can help to identify the appropriate approach to optimizing treatment in patients with loss of response.
Special Edition IBD Dialogue: Therapeutic Drug Monitoring in Clinical Practice 2014·Volume 01 is made possible by an unrestricted educational grant from…