Evidence Supporting High-Dose Use of Biologics in Clinical Practice

Abstract

Biologic therapies have transformed the management of inflammatory bowel disease (IBD). However, a significant proportion of patients demonstrate primary non-response (PNR) or develop a secondary loss of response (LOR) to these agents. Studies using therapeutic drug monitoring (TDM) have demonstrated a correlation between drug concentration and improved outcomes and that inadequate drug concentrations may be accountable for a significant proportion of PNR and LOR. This review aims to evaluate the role for high-dose biologic therapy in the treatment of IBD. Several studies have demonstrated an important role for dose optimization of anti-TNF agents to achieve desired therapeutic outcomes. More recently, there is also evidence for dose optimization and empiric dose escalation of vedolizumab and ustekinumab. With anti-TNF agents, dose optimization results in improved therapeutic outcomes by controlling inflammation and reducing immunogenicity. Immunogenicity may play less of a role with vedolizumab and ustekinumab. There is a role for TDM to guide dose optimization of biologics in IBD. Further prospective studies are needed to determine if there is a role for accelerated induction therapy with these agents and to evaluate target trough concentrations for vedolizumab and ustekinumab.