INTRODUCTION: Ulcerative colitis (UC) is an inflammatory bowel disease with a relapsing - remitting course, whose etiology is still unknown. Mild forms are generally managed with mesalazine, whereas moderate-to-severe disease may be addressed through a stepwise approach, often starting with corticosteroids and immunomodulators, and, when needed, progressing to advanced therapies targeting specific molecular pathways. Even though these therapies have led to substantial improvements in patients' quality of life and prognosis over recent decades, consistent and lasting therapeutic responses remain challenging to attain. AREAS COVERED: this review aims to outline emerging small molecules for UC, emphasizing efficacy and safety data from recent phase II - III clinical trials, including both published studies and ongoing research. We performed a thorough literature search using PubMed, Scopus, and ClinicalTrials.gov, excluding earlier-phase studies, and identified additional relevant articles through reference screening. EXPERT OPINION: it is essential to investigate innovative, safe, and easy-to-administer therapies that target alternative immunological pathways to enhance UC treatment. Some molecules, such as miRNA-124 upregulators, JAKi, S1P modulators, and LANCL2 agonists, may enrich our therapeutic armamentarium in UC management. To further optimize therapeutic strategies, combining small molecules with biologic agents could enhance treatment effectiveness, reduce immunogenicity, and improve long-term durability by targeting complementary inflammatory pathways.
Lanzotti et al. (Sun,) studied this question.