Emerging Therapies for Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic heterogeneous group of diseases that has undergone major advances in the understanding of its etiology and pathogenesis in recent years. The development of biologics had resulted in better overall management of the disease, including lower rates of surgery and better long-term clinical and patient-reported outcomes. Treatment modalities have either been newly developed or extrapolated from their approved use for a different indication. Modes of action and treatment targets have varied as well. Treatments such as vedolizumab and ustekinumab, as well as second-generation corticosteroids have been approved by the US Food and Drug Administration (FDA) for the treatment of IBD. Other agents are currently being developed at various stages of clinical trials including anti-adhesion agents such as etrolizumab and abrilumab, JAK inhibitors such as tofacitinib, and anti-trafficking molecules. Toll-like receptors and phosphatidylcholine are also new promising emerging targets that are being investigated in phase 3 clinical trials. It is projected that many therapies will become available in the coming years if supported by the results of current clinical trials. This will provide IBD patients with a wide array of options and allow physicians to choose the best therapies for each individual patient.

Keywords: Crohn’s disease; Inflammatory bowel disease; Therapy; Ulcerative colitis.

Fig. 1

Proposed pathways and signaling molecules involved in the pathogenesis of IBD, including new developing therapies that target them. IEL intraepithelial lymphocyte, IL interleukin, JAK Janus kinase, MAdCAM mucosal addressin cell adhesion molecule, NF-κB nuclear factor-κB, P phosphorylation, S1P sphingosine-1-phosphate, S1P1 S1P receptor 1, STAT signal transducer and activator of transcription, TE effector T cell, TGF-β transforming growth factor-β, TGF-βR TGF-β receptor, TN naïve T cell, TNF-α tumor necrosis factor-α, TNFR TNF receptor, VCAM vascular cell adhesion molecule. Modified with permission from Coskun. M, Vermeire. S & Nielsen O.H. Novel Targeted Therapies for Inflammatory Bowel Disease. Trends Pharmacol Sci. 2017; 38: 127–142. [1]