Promising biological therapies for ulcerative colitis: A review of the literature

Abstract

Ulcerative colitis (UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants (including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab (anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab (another anti-TNF-α agent), tofacitinib (a Janus kinase inhibitor), and vedolizumab and etrolizumab (integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.

Keywords: Anti-integrin agents; Anti-tumor necrosis factor α agents; Biological therapy; Janus kinase inhibitor; Ulcerative colitis.

Figure 1

A mechanism of action that works to reduce inflammation in the gastrointestinal tract (Reprinted with permission from Takeda Pharmaceutical Co.). Vedolizumab selectively inhibits the movement of a discrete subset of T lymphocytes that preferentially migrate into inflamed GI tissue. Vedolizumab specifically binds to the α4β7 integrin, blocking its interaction with MAdCAM-1, which is mainly expressed on gut endothelial cells. This interaction facilitates lymphocyte homing to the gut and is an important contributor to inflammation that is a hallmark of ulcerative colitis. GI: Gastrointestinal; MAdCAM-1: Mucosal addressin cell adhesion molecule-1; IBD: Inflammatory bowel disease; CCR: Chemokine receptor; IL: Interleukine; IFN-γ: Interferon-γ.