JAK inhibitors

Janus Activated Kinase (JAK) inhibitors are small molecules used in the treatment of ulcerative colitis and potentially in the future, of Crohn's disease. They are available in pill format and are considered less costly medications.

What are JAK inhibitors?

Janus Activated Kinase (JAK) inhibitors are small molecules used in the treatment of IBD. As of September 2022, JAK inhibitors are used to treat ulcerative colitis but some of these medications could later be approved for Crohn’s disease as well. Examples of JAK inhibitors on the market are tofatinib (Brand name: Xeljanz®) and filgotinib (Brand name: Jyseleca®), and examples of those currently undergoing clinical development include upadacitinib (Brand name: Rinvoq®) and deucravacitinib (Brand name: Sotyktu). 

JAK inhibitors are:

  • less costly because they are easier to manufacture, 

  • taken orally as pills, hence reducing the need to get injections or infusions, and 

  • non-immunogenic or less likely to trigger the immune system. This is because, unlike biologics, they are not proteins and therefore they do not trigger anti-drug antibodies in your system. 


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How effective are JAK inhibitors?

In our body, JAKs are enzymes/proteins that travel in pair to specific cell-surface receptors of our immune cells. There, they assist a messenger chemical, called STAT, to deliver its message to the nucleus of the cell that would then drive inflammation. 

However, when taken, JAK inhibitors block of some of that intracellular (“inside the cell”) STAT signaling. By doing so, these medications help to reduce inflammation as well as the occurrence of symptoms associated with inflammation in IBD, e.g. pain in the abdomen, diarrhea, constipation.  

As such, JAK inhibitors have been developed to treat inflammation of the gastrointestinal tract and, at present, to induce and maintain remission in people living with colitis. The efficacy of JAK inhibitors is also being tested for Crohn’s disease and so far, the results related to upadacitinib (Rinvoq®) for Crohn’s disease seem promising. 


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Side effects and risks of use

Small molecules, like JAK inhibitors, have more side effects than other medications on average because they are not as focused or targeted. Some of these side effects include: 

  • Increasing the risk of infection, such as for Shingles. The vaccine for Shingles is therefore recommended for people over the age of 18 who intend to take JAK inhibitors.

  • Elevating your blood cholesterol.

  • Increasing the risk of blood clots (thromboembolism), cardiac events like heart attacks, cancers (those of the skin and lungs in particular), and death. However, it is important that the four categories of side effects in this bullet point are mostly seen in elderly people treated for rheumatoid arthritis with these medications. People living with colitis who are treated with JAK inhibitors do not usually experience the symptoms mentioned here. 


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Resources

Video: JAK Inhibitors and Inflammatory Bowel Disease

Watch this video (6 min) to learn more about JAK inhibitors used in the treatment of Crohn's disease and ulcerative colitis, including how these medications work in IBD, what they are used for, which types of patients can access JAK inhibitors, potential benefits, side effects, and risks.

Speaker: 

Dr. John K. Marshall (MD, MSc, FRCPC, CAGF, AGAF), Professor of Medicine, Director, Division of Gastroenterology, McMaster University.


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