Tofacitinib in the Management of Ulcerative Colitis Refractory to Anti-TNF and Anti-Integrin Therapies

Abstract

-Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib. HEADINGS -Proctocolitis, therapy. Biological factors. Monoclonal antibodies. Janus kinase inhibitors, therapeutic use.Declared conflict of interest of all authors: Teixeira FV is a speaker and consultant for Janssen, Ferring, Abbvie and Takeda; advisory board for Ferring and Janssen. Damião AOMC is a speaker and consultant for Abbvie, Janssen, Pfizer and Takeda. He is also an employee of Nestle. Kotze PG is a speaker and consultant of Abbvie, Janssen, Takeda and Pfizer. Disclosure of funding: no funding received Studied carried out at Gastrosaúde,

Letter: thromboembolic and cardiovascular events with tofacitinib in ulcerative colitis—two cases in real world clinical practice

“…Tofacitinib was approved for UC in Brazil in 2019, and experience with the drug is in its early phases . We recently saw two important adverse events which could be related to these issues.…”