Emerging drugs for the treatment of moderately to severely active ulcerative colitis: review of phase II and III clinical trials

ABSTRACT

Introduction

Current therapeutic options for patients with ulcerative colitis comprise monoclonal antibodies against tumor necrosis factor (TNF), alpha4/beta7 integrin, and interleukin (IL)12/23 as well as small molecules such as tofacitinib, upadacitinib, ozanimod, and filgotinib. However, many patients fail to respond to these agents or have loss of response over time. Therefore, there is a large unmet clinical need for new therapeutic agents.

Areas covered

Here, we review recent phase 2/3 studies in active ulcerative colitis and discuss preliminary data on the efficacy (clinical, endoscopic, and histologic remission) and safety of novel drugs including Janus kinase (JAK) inhibitors, IL23 blockers, integrin inhibitors, and S1P1R modulators.

Expert opinion

We highlight the potential impact of these agents for the future therapeutic landscape of this disease with special emphasis on clinical impact, unmet needs, safety aspects, and advanced combination therapy.

KEYWORDS:

• Inflammatory bowel disease
• ulcerative colitis
• treatment
• phase II and phase III trials

Article highlights

• Recent findings have highlighted a key role of the activation of the mucosal immune system in the pathogenesis of ulcerative colitis

• Several new drugs have been recently tested in controlled clinical phase 2/3 trials in ulcerative colitis

• Promising results have been obtained with new drugs targeting Janus kinases and the cytokine IL-23

• It is likely that some of these new compounds will be available for clinical use in the future thereby expanding our armamentarium for clinical therapy

Declaration of interest

F. D’Amico has served as a speaker for Sandoz, Janssen, Galapagos, and Omega Pharma. S. Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millennium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

L Neurath wrote the article and created tables and figures. F D’Amico and S Danese critically revised the manuscript. The manuscript was approved by all authors.

Additional information

Funding

This paper was not funded.