Abstract
Inflammatory bowel diseases (IBDs), mainly represented by Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development.
Highlights
Inflammatory bowel diseases (IBDs) refer mainly to Crohn’s disease (CD) and ulcerative colitis (UC)
Small molecules drugs (SMDs) that use a broad range of novel pharmacological pathways, e.g., Janus kinases (JAKs) inhibitors, sphingosine-1phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for IBDs (Figure 1)
JAKs are activated in pairs through cytokine binding and, in turn, activate cytosolic DNA-binding proteins named signal transducers and activators of transcription (STATs)
Summary
Inflammatory bowel diseases (IBDs) refer mainly to Crohn’s disease (CD) and ulcerative colitis (UC) They are chronic, disabling diseases that may lead to severe medical and surgical complications and to extradigestive manifestations [1,2]. Biomolecular drugs are complex polypeptide chains with up to tertiary structures and a net higher molecular weight (mean: 150 kDa) [6] Their goal is to induce and maintain clinical remission, prevent complications, and avoid longterm steroid use. In IBD, a step-up strategy is currently the standard of care: guidelines mostly advise the use of biomolecular drugs in moderate to severe IBD when first-step medications such as steroids, aminosalicylates, and immunomodulators have failed or are insufficient to induce or maintain remission. A top-down strategy, that is, initial treatment with biologics or immunomodulators, is considered, especially in patients with a complicated or extensive disease with poor prognostic factors [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
