A critical review of ustekinumab for the treatment of active ulcerative colitis in adults

ABSTRACT

Introduction

Ustekinumab is a humanized monoclonal antibody, targeting the p40 subunit common to both human interleukin 12 and 23, approved by the European Medicines Agency and US Food and Drug Administration for the treatment of moderate-to-severe ulcerative colitis.

Areas covered

In this review, the results of the phase 3 UNIFI and the real-world studies assessing the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis are discussed, as well as limitations of these studies. Predictive factors of response, the interest of therapeutic drug monitoring and the positioning of ustekinumab in specific situations are also addressed. Finally, in the light of data presented, the positioning of ustekinumab in the therapeutic algorithm of ulcerative colitis will also be considered.

Expert opinion

Ustekinumab has been shown to be effective to induce and maintain clinical, endoscopic and histologic remission in moderate-to-severe ulcerative colitis both in phase 3 and real-world studies, with a favorable safety profile. Overall, its favorable risk–benefit ratio, its efficacy on extra-intestinal manifestations and in biologics failure patients make ustekinumab an ideal candidate as first, second, or third-line therapy in ulcerative colitis.

KEYWORDS:

• Ustekinumab
• ulcerative colitis
• UNIFI
• real-world studies
• efficacy
• safety

Article highlights

• Ustekinumab, a humanized monoclonal antibody, targeting the p40 subunit common to both human interleukin 12 and 23, is effective to induce and maintain clinical, endoscopic and histologic remission in moderate-to-severe ulcerative colitis both in the phase 3 and real-world studies

• The clinical benefit could be observed in both biologic-naive and biologic-failure patients (even in patients who have failed 2 biologics with different targets)

• Evidence from real-life experiences are accumulating, confirming the favorable safety profile which had emerged from the randomized control trial

• Among other advantages, ustekinumab has an easy mode of administration and a low rate of neutralizing antibodies and therefore a low immunogenicity

• Ustekinumab can be positioned either as a first biologic agent after failure of conventional therapy, or as a valid alternative in patients failing anti-TNF and/or vedolizumab

Abbreviations

AE, adverse event; CARP, chronic antibiotic-refractory pouchitis; CD, Crohn’s disease; CRP, C-reactive protein; CS, corticosteroid; IBD, inflammatory bowel disease; EIMs, extraintestinal manifestations; FDA, Food and Drug Administration; IBDQ, inflammatory bowel disease questionnaire; IL, interleukin; IPAA, ileal pouch anal anastomosis; IQR, interquartile range; IMID, immune-mediated inflammatory diseases; IV, intravenous; JAK, Janus kinase; LTE, long-term extension; PRO, patient reported outcomes; RCT, randomized control trial; SAE, serious adverse event; SC, subcutaneous; SHS, short health scale; STRIDE, Selecting Therapeutic Targets in Inflammatory Bowel Disease; TNF- α, tumor necrosis factor-α; UC, ulcerative colitis

Declaration of interest

S Vieujean has served as a speaker for: AbbVie, Ferring, Janssen and Takeda. E Louis discloses: research grants from AbbVie, Falk, Ferring, Janssen, Pfizer, and Takeda; educational grants from AbbVie, Fresenius Kabi, Janssen and Takeda; speaker fees from AbbVie, Falk, Ferring, Galapagos, Janssen, Pfizer and Takeda; advisory board roles for AbbVie, Arena, BMS, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Pfizer and Takeda; and consultant role for AbbVie. S Danese has served as a speaker, consultant, and advisory board member for: AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plow, UCB Pharma and Vifor. L Peyrin-Biroulet discloses: personal fees from consulting for AbbVie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor and Ysopia; grants from Celltrion, Fresenius Kabi and Takeda; personal fees from lectures for: AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Pfizer, Sandoz, Takeda, Tillots, Viatris 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

Reviewers on this manuscript have disclosed: speaker, consultant, and/or advisory board roles for AbbVie, Janssen, Pfizer and Takeda; research support from Galápagos NV and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships to disclose. Janssen provided a scientific accuracy review at the request of the journal editor.

Data availability statement

The data underlying this article are available in the article.

Additional information

Funding

This paper was not funded.