Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors

Edoardo Troncone, Irene Marafini, Giovanna Del Vecchio Blanco, Antonio Di Grazia, Giovanni Monteleone Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, ItalyCorrespondence: Giovanni MonteleoneDipartimento di Medicina dei Sistemi, Università di Roma “Tor Vergata”, Via Montpellier, 1, Rome 00133, ItalyTel +390620903702Fax +390672596391Email Gi.Monteleone@Med.uniroma2.itAbstract: Crohn’s disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease(IBD) in human beings, are chronic relapsing-remitting disorders of the gastrointestinal tract, which usually require lifelong therapies. For many years, IBD have been managed with corticosteroids, aminosalicylates and immunosuppressants (ie, thiopurines). The advent of biologic therapies (anti-TNF-α agents) has significantly improved the outcome of IBD patients in terms of prolonged clinical remission, corticosteroid sparing, achievement of mucosal healing and prevention of disease-related complications. Nevertheless, primary failure or loss of response to biologics occur in about 50% of patients treated with these drugs. Therefore, the need for new effective treatments for such patients has critically emerged as an urgent priority. With this regard, several small-molecule drugs (SMDs) targeting lymphocyte trafficking (ie, sphingosine-1-phosphate receptor modulators) and the JAK/STAT pathway (eg, tofacitinib) have been recently developed and tested in IBD. In particular, JAK inhibitors are oral compounds characterized by short half-life, low antigenicity and the ability to dampen several pro-inflammatory pathways simultaneously. Tofacitinib, a pan-JAK inhibitor, has shown good efficacy and safety in UC clinical trials and has been recently approved for the treatment of UC patients. In this review, we analyze the main evidence supporting the use of JAK inhibitors in UC and explore the unanswered questions about the use of this class of drug in UC.Keywords: inflammatory bowel disease, tofacitinib, JAK/STAT pathway, small molecule drugs