Tailoring treatment to the individual patient: drug monitoring

Understanding why drug concentrations vary between patients and which drug concentrations are associated with efficacy allow the development of rational treatment algorithms. Factors that affect the clearance of monoclonal antibodies include: (1) the presence of antidrug antibodies (increased clearance), (2) concomitant immunosuppression (decreased clearance), (3) increased serum CRP concentration (increased clearance), (4) decreased serum albumin concentration (increased clearance), (5) decreased body weight (increased clearance), and (6) increased fecal infliximab concentration (increased clearance). These factors can result in marked variability in drug clearance. Higher serum infliximab and adalimumab concentrations are associated with increased rates of clinical response and mucosal healing, and lower rates of colectomy. Treatment algorithms incorporate the following principles: (1) patients who have symptoms of active disease and in whom high concentrations of antibodies to infliximab or adalimumab are present should switch to another TNF antagonist, (2) patients who have symptoms of active disease and in whom there are low concentrations of infliximab or adalimumab should have dose intensification, and (3) patients who are negative for antidrug antibody and who have a therapeutic drug concentration should undergo evaluation to confirm the presence of active disease by endoscopy or radiology studies, and if active disease is confirmed, then these patients should discontinue anti-TNF therapy and switch to another class of medications or consider surgical options.