Guideline review: Tofacitinib for adults with moderately to severely active ulcerative colitis - NICE guidance

Abstract

Tofacitinib is an oral, Janus kinase (JAK) molecule, which selectively inhibits Janus-associated tyrosine kinases JAK1 and JAK3. It has already shown efficacy in the treatment of rheumatoid arthritis and the prevention of organ allograft rejection in kidney transplantation. Two separate phase III placebo-controlled trials, assessing 8-week efficacy of tofacitinib induction for ulcerative colitis (UC), demonstrated superiority when compared with placebo. Tofacitinib also demonstrated robust efficacy versus placebo in the 52-week maintenance component of the same study. Tofacitinib has been recommended by the National Institute for Health and Care Excellence as an effective treatment option for adult patients with moderate to severe UC when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment. We review the guidelines and provide brief commentary on the post hoc analysis related to lipid increases and thromboembolism risk, which have lead to changes in current therapeutic guidance.

Keywords: inflammatory bowel disease; ulcerative colitis.

Figure 1

The mechanism of action of tofacitinib: (1) a cytokine binding to its cell surface receptor leads to receptor polymerisation; (2) tofacitinib inhibits the phosphorylation and activation of the Janus-associated tyrosine kinases (JAKs), JAK1 and JAK3; (3) JAKs cannot phosphorylate the cytokine receptors, therefore the receptors cannot dock signal transducers and activators of transcription (STATs); (4) as STATs are not phosphorylated or activated, gene transcription/cytokine production is inhibited.