Effectiveness and Safety of Tofacitinib in the Management of Ulcerative Colitis: A Brazilian Observational Multicentric Study

Abstract

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing–remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, JAK inhibitor, more selective for JAK 1 and JAK 3, which reduces the inflammatory process involved in the pathogenesis of UC. METHODS Retrospective observational multicentric study of patients with ulcerative colitis (UC) who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo Score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. RESULTS From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52 and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5% and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17,8% needed colectomy. CONCLUSION Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.

Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness

“…Tofacitinib preferentially inhibits JAK1 and JAK3 signaling, and to a lesser extent JAK2 9 . Despite the increasing utilization of JAK inhibitors, primary and secondary nonresponse occurs in more than 30% and 25% of patients, respectively [10][11][12][13] . Although several reports have analyzed clinical data, gut microbiota, and mucosal transcriptomes to identify distinguishing factors associated with responsiveness to inhibitors of TNFα and α4β7 integrins [14][15][16][17] , there are little data addressing JAK inhibitors.…”