The Role of Novel Small Molecule Drugs in the Management of Inflammatory Bowel Disease

Treatment algorithms have traditionally been based on biological therapy when conventional therapy was not successful in controlling inflammatory bowel disease (IBD). Novel small molecule drugs (SMDs) for IBD include the Janus Kinase (JAK) inhibitors Tofacitinib, Filgotinib and Upadactinib and the sphingosine-1 phosphate (S1P) inhibitors Ozanimod and Etrasimod. SMDs have advantages over biologics, such as oral administration, lack of immunogenicity, and rapid onset of action. All agents are effective in treating ulcerative colitis, while Upadactinib is the only SMD for Crohn's disease. There is growing interest in the use of JAK inhibitors for acute severe colitis. However, safety profiles are distinct from biologics. Clinicians need to be aware of the need for additional lipid monitoring for JAK inhibitors. S1P inhibitors require pre-treatment electrocardiograms to reduce the risk of bradycardia and retinal exams at least in high-risk patients to avoid macular oedema. In this review we highlight the key evidence on efficacy and safety for general hospital physicians.