Mechanisms of molecular resistance and predictors of response to biological therapy in inflammatory bowel disease

Biological therapy has led to marked improvements in treatment of patients with inflammatory bowel disease, and an increasing number of drugs has been approved for treatment. However, only a subgroup of patients responds to therapy, highlighting the need to identify biomarkers for therapeutic response to allow personalised medicine in inflammatory bowel disease. Potential markers of response to biological therapy have been identified; however, studies also suggest that changes in the composition of immune cell infiltrates in response to therapeutic pressure lead to molecular resistance to these drugs. For instance, the cytokine interleukin 23 has been identified as a driver of evasion of apoptosis in response to anti-tumour necrosis factor drugs in patients with Crohn's disease, leading to expansion of apoptosis-resistant T cells and drug resistance. In this Review, we examine the concept of molecular resistance to biological therapy and discuss implications for future therapy.