Small Molecules as Advanced Therapy for the Treatment of Inflammatory Bowel Disease, Particularly Regarding Ulcerative Colitis

Small molecules used to treat inflammatory bowel disease (IBD) are orally administered therapies that offer a rapid onset without immunogenicity. Currently, three Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, and upadacitinib), two Sphingosine-1-phosphate receptor (S1PR) modulators (ozanimod and etrasimod), and one alpha4-integrin antagonist (carotegrast methyl) are available in Japan. Each JAK inhibitor has its own efficacy and safety profile: Upadacitinib is the most effective, despite its higher frequency of associated adverse events, whereas filgotinib has a weaker efficiency but with fewer adverse events. Although tofacitinib has been associated with major cardiovascular events and thromboembolism in patients with rheumatoid arthritis, such findings have not been demonstrated in patients with ulcerative colitis. S1PR modulators have similar mechanisms of action, except for the titration at the beginning and the recovery time of the lymphocyte count after discontinuation. Overall, small-molecule drugs are effective and convenient options for IBD, with safety profiles that require individual patient assessment.