Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis

ABSTRACT

Introduction

Ustekinumab is a human IgG1 kappa monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23 and blocks the binding of these cytokines to the IL-12Rβ1 chain of their receptors. Ustekinumab is approved for treating moderate-to-severe ulcerative colitis (UC).

Areas covered

We reviewed the mechanism of action, pharmacokinetics, efficacy, and safety of ustekinumab. Future challenges for optimizing UC treatment with ustekinumab are discussed.

Expert opinion

Ustekinumab has favorable clinical efficacy and safety profiles for moderately-to-severely active UC. Ustekinumab is the first biologic for targeting IL-12/IL-23 pathways. Therefore, ustekinumab can be a therapeutic option following the failure of other biologics, including anti-tumor necrosis factor-α antagonists and anti-α₄ß₇ integrin antagonists. However, the positioning of ustekinumab in the therapeutic strategy for UC remains unclear. The efficacy of combinations of ustekinumab and immunomodulators over ustekinumab monotherapy has not been supported in studies. Ustekinumab is a human immunoglobulin G monoclonal antibody with low immunogenicity. Therefore, ustekinumab monotherapy, which should be safe, could be sufficient for treating UC. Further studies are required to understand the efficacy and safety of ustekinumab in patients with UC, particularly in special situations, and to optimize UC treatment with ustekinumab.

KEYWORDS:

• Ustekinumab
• ulcerative colitis
• safety evaluation
• biologics

Drug Summary box (Box 1)

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Acknowledgments

The authors thank Joe Barber Jr., PhD, from Edanz for editing a draft of this manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Janssen provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.