Targeting IL12/23 in ulcerative colitis: update on the role of ustekinumab.

As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline. Interleukin (IL)-12 and IL23 are two key cytokines responsible for promoting and perpetuating bowel inflammation in IBD. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of both cytokines, and it was recently approved for the treatment of ulcerative colitis (UC). In the pivotal phase III UNIFI trial, ustekinumab showed a superiority over placebo in both clinical and endoscopic outcomes; furthermore, it was characterized by a favorable safety profile, with a similar rate of adverse events as compared with placebo. Recent evidence from real-life experiences have started accumulating, generally confirming the effectiveness and safety figures emerged from the registration studies. However, most of these observational studies enrolled multirefractory patients; moreover, comparative data with other target therapies are lacking, leaving physicians without clear indications about the appropriate positioning of ustekinumab in the therapeutic pipeline for UC. This review examines the basis of targeting IL12-23 in UC therapy and summarizes the data from both clinical trials and real-life studies, to highlight the main evidence already available and the research gaps that need to be filled for the optimal usage of ustekinumab in UC.

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© The Author(s), 2022.

Déclaration de conflit d'intérêts

Conflict of interest statement: The authors declare the following conflicts of interest: Daniela Pugliese received speaker fees from AbbVie, MSD, Takeda and Janssen, Pfizer; advisory board fees from Pfizer. Giuseppe Privitera received consultancy fees from Alphasigma. Antonio Gasbarrini reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and Sanofi S.p.A, personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A, and personal fees for acting on advisory boards for VSL3 and Eisai. Alessandro Armuzzi: consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi-Tanabe, Nikkiso, Novartis, Pfizer, Sandoz, Samsung Bioepis, Takeda; and research grants from MSD, Pfizer, Takeda and Biogen. All the other authors have no conflict of interest to declare.