Advances in Therapeutic Drug Monitoring of Biologic Therapies in Inflammatory Bowel Disease: 2015 in Review.

OPINION STATEMENT: Monoclonal antibody therapy directed against tumor necrosis factor-alpha (anti-TNFs) has revolutionized the care of patients with Crohn's disease and ulcerative colitis. These large proteins are potentially immunogenic. Early clinical trials demonstrated an association with both serum concentrations of these agents as well as the presence of antidrug antibodies generated by the host with loss of response. More recent research has provided further evidence to confirm the impact of low drug trough concentrations and antidrug antibodies on subsequent clinical course in CD and UC. Given these clinical implications, treatment algorithms have been developed to aid clinicians in interpreting trough drug levels and antibody concentrations in those with confirmed active disease. Several studies have demonstrated the utility of these approaches. Furthermore, there are growing data supporting the use of therapeutic drug monitoring in a prospective fashion in those patients who are clinically stable on anti-TNF therapies to ensure they are receiving appropriate dosing and have not yet developed antibodies. In addition, for those who have developed low-level antibodies, increasing the dose of an anti-TNF or adding an immunomodulator may help to overcome this immunologic response. Further research is required to assess these proposed strategies, as well as to determine the role of trough drug level assessment and antibody testing for new anti-TNFs and biologic medication with alternative mechanisms of action.