An Overview of Emerging Trends and Technologies in Ulcerative Colitis
Authors: Mendell Ari , Le Kim , Vannabouathong Chris , Mahood Quenby 
Published: July 2023

This report provides an overview of the evolving therapeutic landscape for moderate to severe ulcerative colitis (UC), including recent changes to clinical practice guidelines, key trends in therapeutic strategies, and new or emerging treatment options, with a focus on biologics and small-molecule therapies.
Recent guidelines on the medical management of patients with UC include those of the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and European Crohn’s and Colitis Organisation (ECCO), which were published in 2019, 2020, and 2022, respectively. These guidelines provide an accurate reflection of how clinical practice has changed to incorporate newer therapies that have entered the market and newer evidence that has been published since the release of the Canadian guidelines in 2015. The ACG, AGA, and ECCO guidelines all recommend use of a tumour necrosis factor (TNF) antagonist, vedolizumab, or tofacitinib for induction of remission in patients with moderate to severe UC; the AGA and ECCO guidelines also recommend ustekinumab as an option and recommend vedolizumab over adalimumab, whereas the AGA guidelines recommend early use of biologic drugs over a step-up approach after failure of 5-aminosalicylates.
Two important trends in therapeutic strategies for UC include changes in the use and definition of treatment targets and recommendations regarding therapeutic drug monitoring (TDM).

The 2021 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) guidelines provide contemporary consensus recommendations for using new and updated targets throughout an individualized treatment timeline in patients with inflammatory bowel disease (IBD). Although histologic remission is not considered a formal UC treatment target in STRIDE-II, it is acknowledged as an adjunctive measure to endoscopic remission to represent a deeper level of healing and is the focus of many current studies.
The use of TDM emerged from challenges associated with the use of older biologics (primarily TNF antagonists), which posed difficulties related to immunogenicity and dosing. The relevance of TDM for newer biologics with different mechanisms of action, reduced immunogenicity, and fixed dosing (e.g., vedolizumab and ustekinumab) is a topic of ongoing debate. Although AGA guidelines on TDM in IBD and expert consensus statements support the use of reactive TDM for patients with UC who lose response to a TNF antagonist, evidence gaps remain regarding appropriate use of proactive TDM, utility of TDM for small molecules and biologics outside of the TNF antagonist class, and consistent target concentration thresholds to guide dose changes.

There is a substantial pipeline of new and emerging drugs for the treatment of adults with moderate to severe UC, with many in phase IIb or III of clinical development; several notable trends of emerging pharmacotherapies exist, including an increasing number of Janus kinase inhibitors, several therapies with biologic targets that are new in UC (e.g., interleukin-23 antibodies, TNF-like ligand 1A inhibitors), an increasing number of oral therapies, and the first combination of 2 biologic therapies in UC.
The Canadian health care system should be prepared to adapt to the rapidly evolving treatment landscape and potential clinical practice changes in moderate to severe UC. Drugs with new mechanisms of action in the treatment area and the new paradigm of combination therapy with multiple biologics of different classes may lead to improved patient outcomes but can also further complicate the treatment decision-making process. Therefore, it is important for health care providers to stay up to date on new and upcoming treatment options, which may require educational initiatives for both providers and patients as well as updates to the Canadian treatment guidelines. Overall, potential changes on the horizon may have substantial implications for the health care system given the prevalence of UC in Canada, the costs of advanced therapies, and the increasing number of available treatment options.