Positioning ustekinumab in moderate-to-severe ulcerative colitis: new kid on the block

ABSTRACT

Introduction: Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract. Dysregulated innate and adaptive immune pathways contribute to intestinal inflammation in IBD, and cytokines, including IL-12 and IL-23, play a key role. The blockade of both IL-12 and IL-23 may have an impact on different pathways of inflammation and could be effective for the treatment of inflammatory bowel diseases.

Ustekinumab is a fully human IgG1κ monoclonal antibody which binds to the shared p40 protein subunit of IL-12 and −23. It is currently approved for several immune-mediated diseases such as moderate to severe plaque psoriasis, psoriatic arthritis, and Crohn’s disease, and has shown promising results in UC.

Areas covered: A review of the literature was performed to understand several aspects including the role of IL-12 and −23 in UC, the potential therapeutic role of ustekinumab in inflammatory bowel disease, and the positioning of ustekinumab in the therapeutic algorithm of UC, based on extrapolated data from available randomized clinical trials.

Expert opinion: Ustekinumab is effective and safe in UC, and shows potential advantages compared to other drugs in moderate-to-severe UC.

KEYWORDS:

• Ulcerative colitis
• ustekinumab
• biologics
• monoclonal antibodies
• Il-23
• Il-12
• inflammatory bowel disease

Article highlights

• IL-12 and IL-23 play a key role in triggering and maintaining chronic inflammation in the colon of UC patients

• Ustekinumab blocks the p40 subunit of IL-12 and IL-23 and is effective in treating several immune-mediated disorders, such as psoriasis, psoriatic arthritis, and Crohn’s disease.

• Ustekinumab has been investigated in moderate-to-severe UC patients failing conventional and/or biological therapies

• Ustekinumab results show effectiveness in inducing and maintaining clinical, endoscopic, and histological remission, and maintenance of remission up to 1 year.

• The safety profile of ustekinumab in UC was not different from placebo, and immunogenicity was very low and not clinically relevant

• Ustekinumab represents a valid therapeutic choice in moderate-to-severe patients with UC, both in naïve subjects or patients previously exposed to biologics.

This box summarizes the key points contained in the article.

Declaration of interest

S Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, α Wasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson. G Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. L Peyrin-Biroulet has received consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, Amgen, and Sandoz; Lecture fees from Merck, Abbvie, Takeda, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi, and HAC-pharma. 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

One of the reviewers on this manuscript has received lecture and educational fees form Janssen, Takeda, Pfizer. All additional peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.