Therapy of Inflammatory Bowel Disease: What to Expect in the Next Decade

David A. Leiman; Gary R. Lichtenstein


Curr Opin Gastroenterol 

In This Article

Antagonist to Janus Kinase

Although ustekinumab may eventually provide a medical option for patients with Crohn's disease when anti-TNF therapy fails, its role for ulcerative colitis is not well established. Blockade of the Janus kinase (JAK) has shown promise as an antiinflammatory approach in patients with autoimmune conditions such as psoriasis, and its use in ulcerative colitis may provide an alternative to surgery when current medications fail. The JAK family of tyrosine kinases mediates signal transduction for a variety of inflammatory cytokines including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.[26]

Tofacitinib (CP-690550), an oral inhibitor of JAK 1, 2, and 3, was evaluated in patients with ulcerative colitis. In a phase II study, it was shown to significantly induce remission after 8 weeks compared with placebo. Although some safety concerns exist with respect to elevated levels of low-density lipoprotein cholesterol, we expect that this will be a matter of investigation over the next several years and has potential to be an alternative in the ulcerative colitis arsenal.