The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

Abstract

The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

Fig. 1. Mechanism of action of existing and investigational biologic agents in IBD

TNF tumor necrosis factor, Th1 T helper cell 1, MAdCAM-1 mucosal vascular addressin cell adhesion molecule 1

Fig. 2. Mechanism of action of new investigational small-molecule agents in IBD

(a) JAK janus kinase, STAT signal transducer and activator of transcription protein, PDE4 phosphodiesterase type 4, cAMP cyclic adenosine monophosphate, PKA protein kinase A, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, CREB cAMP response element-binding protein, (b) S1P sphingosine-1 phosphate