June 3, 2016

New Class of Drugs Called JAK Inhibitors Appear Effective in Crohn’s Disease

By megm

Inflammatory Bowel Disease (IBD) is an immune-mediated chronic inflammation of the gastrointestinal tract. There are two types of IBD, Crohn’s disease and ulcerative colitis; both manifest as chronic immune-mediated inflammation of the gastrointestinal system. While they both cause similar symptoms, they are managed differently. Crohn’s disease may affect any part of the gastrointestinal system, from the mouth to the anus. Ulcerative colitis, however, is limited to the colon, otherwise known as the large intestine. It is estimated that 1.4 million Americans have IBD, which tends to run in families and affects males and females equally.

Normally, the cells and proteins that make up the immune system protect individuals from infection. In people with IBD, however, the immune system mistakes food, bacteria, and other materials in the intestine for foreign or invading substances. When this happens, the body sends white blood cells into the lining of the intestines, where they produce chronic inflammation and ulcerations—called an autoimmune response.

Crohn's disease is characterized by inflammation and cytokine production which require a family of kinases for their production and activation. These kinases includes JAK1, 2, and 3, as well as tyrosine kinase 2. Inhibition or blocking of the JAK1 can suppresses the production of proinflammatory cytokines such as interleukins 2 and 6.

Filgotinib is a selective oral JAK1 inhibitor and the results of a study evaluating it in the treatment of moderate-to-severe Crohn's disease were recently reported. Overall 59% of patients with Crohn’s responded to treatment and 47% achieved a clinical remission.

Filgotinib was well tolerated and quality of life, as measured on the Inflammatory Bowel Disease Questionnaire, improved for all aspects of the quality-of-life questionnaire, including bowel symptoms, systemic symptoms, emotional status, and social functioning.

The investigators concluded that Filgotinib was effective in Crohn's disease and showed improvements in quality of life for patients who were either TNF-naive or -failures.

Reference: Vermeire S, et al. Filotinib (GLPG0634), an oral JAK1 selective inhibityor, induces clinical remission in patients with moderate-to-severe Crohn's disease: Results from the phase 2 FITZROY study interim analysis. DDW 2016; Abstract 812c.

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