Michael Chiorean, MD, on the Optimal Use of JAK Inhibitors in IBD

Dr Chiorean discusses his presentation at the Advances in Inflammatory Bowel Diseases 2021 regional meeting on April 16 on how to use Janus kinase inhibitors in managing inflammatory bowel disease.

Michael Chiorean, MD, is director of the IBD Center at Virginia Mason Medical Center in Seattle, Washington.

TRANSCRIPT:

Dr. Michael Chiorean:  Hello. I'm Dr. Michael Chiorean, and I'm a gastroenterologist at Virginia Mason Medical Center in Seattle. In the most recent advances in inflammatory bowel disease, I went over the topic of JAK inhibitors for the management of IBD.

They work by inhibiting an intracellular signaling pathway called JAK/STAT that mediates the activity of several proinflammatory cytokines, which play a key role in the pathogenesis of IBD as well as other immune-mediated inflammatory conditions such as rheumatoid arthritis, psoriasis, vasculitis but also certain allergic disorders.

Being small molecule therapeutics, they have clear advantages over other targeted therapies, and then they can be administered orally. They have a very fast onset of action.

Some, such as tofacitinib, work as well in patients who are bio-naîve as in patients who have failed prior biologic therapies, and plus, they don't generate immunogenicity, meaning that people will not develop antibodies against them after taking them short or long term.

Now, the beauty of this class of drugs lies in the fact that they can be custom-designed to target a specific JAK subunit, thus making them selective for a specific pathway or a cytokine signaling.

This not only narrows their therapeutic spectrum to a certain disease or group of immune-mediated disorders but may also increase their efficacy by allowing us to increase the dose, particularly during induction, while at the same time, maintaining a good safety profile by reducing the risk of off-target side effects.

Some JAK1-selective agents have already been approved for other indications such as rheumatoid arthritis, psoriasis, or psoriatic arthritis while being in advanced stages of development for inflammatory bowel disease, both ulcerative colitis and Crohn's disease.

One other way to tweak these molecules or the mechanism of action is to create candidate JAK inhibitors that is not absorbable through the gut and thus deliver all their activity in the gut and avoiding most of the systemic side effects.

For all these reasons, I suspect that this class of drugs, the JAK inhibitors, will continue to see a substantial growth and expansion over the next few years. We'll see an increase use of these therapeutics both in IBD as well as other immune-mediated disorders in the next decade.

Not only as single therapy but also these drugs have the potential to be used in combination with other complementary therapeutics in particular including biologics during induction therapy, for instance, in patients with more severe or refractory forms of IBD so that to give us improved efficacy outcomes.

Please stay tuned. Join us now or for future advances in IBD events to learn about these newer trends and listen to discussion and debates on hot topics in IBD virtually this year but hopefully live again next year. Thank you.

Chiorean, M. The optimal use of JAK inhibitors in IBD. Presented at: Advances in Inflammatory Diseases 2021 regional meeting, April 16, 2021. Virtual.