Tofacitinib for the treatment of ulcerative colitis

ABSTRACT

Introduction: Management of patients with active ulcerative colitis (UC), one of the most frequent inflammatory bowel diseases in human beings, is mainly based on the use of mesalamine and corticosteroids. Since in the long-term, these two drugs may be ineffective in nearly one third of the patients, immunosuppressants and/or biologics are needed to control disease activity.

Areas covered: The marked activation of JAK/STAT molecules in inflamed mucosa of UC patients and the demonstration that UC-associated mucosal injury is driven by soluble factors that signal through JAK/STAT pathways led to investigation of JAK inhibitors for the treatment of active UC. Tofacitinib, an oral inhibitor of the cytokine-driven JAK-STAT signalling cascade, has recently been proposed for the treatment of moderate-to-severe UC. Phase 2 study showed the efficacy of tofacitinib to induce clinical and endoscopic improvement/remission and the safety profile of the drug. Herein the authors review this compound.

Expert opinion: The results obtained from clinical trials with tofacitinib suggest that this drug could be a new treatment option for patients with moderate to severe UC. However, further experimentation is needed to assess the efficacy of this drug in selected subgroups of patients as well as to maintain remission and to determine the long-term safety profile of the drug.

KEYWORDS:

• JAK
• STAT
• CD4+ T cells
• intestinal inflammation
• cytokines
• inflammatory bowel diseases

Declaration of interest

The authors have received research funding for the work on cytokines in IBD from Fondazione U. Di Mario (Rome, Italy). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.