Dr Axelrad reviews his talk on the use of JAK inhibitors for the treatment of inflammatory bowel diseases which he gave at the AIBD regional meeting September 30.

Jordan Axelrad, MD, is director of Clinical and Translational Research and an inflammatory bowel disease specialist at NYU Langone Health in New York City, New York.

--

TRANSCRIPT:

Jordan Axelrad:
I'm Jordan Axelrad, and I'm an inflammatory bowel disease specialist at NYU Langone. You just heard me speak at AIBD Regional virtual meeting. And I've been discussing JAK inhibitors. JAK kinase inhibitors are oral, organic, small molecules that are typically work intracellularly, have a very short half-life, and there are no issues with immunogenicity, such as antibody formation, as we've seen with biologics. They differ in several other ways, but more importantly, that these drugs block JAK-stat signaling and subsequently block cytokine growth factor signaling, which results in its effectiveness in inflammatory bowel diseases.
In particular, JAK inhibitors have proven efficacy in biologic failures, which is very important in our field, where many patients are increasingly refractory to various biologic agents. Currently, JAK inhibitors, tofacitinib and upadacitinib are approved in ulcerative colitis, hopefully with some promising data soon in Crohn's disease as well.

In the United States, these JAK inhibitors are in particular reserved for patients who are already anti-TNF failures, in particular. In other places worldwide JAK inhibitors are sometimes utilized prior to biologic failure. But in the United States, given there's some safety signals, JAK inhibitors are generally reserved once a patient has failed a biologic anti-TNF agent in particular.
Other than the efficacy of these drugs, which again have demonstrated that they work pretty well. There are many side effects. Some of those side effects include infections, in particular herpes zoster, which is the most frequently reported adverse event. This is why it's very important for patients to be vaccinated against shingles. And also, there have been reports, but generally limited to an older population with rheumatoid arthritis, of some major cardiovascular events, such as stroke and MI, in addition to an increased risk of certain skin cancers, non-melanoma skin cancers, and even some reports of lymphoma and lung cancer. However, these risks, specifically the risks of cardiovascular events and malignancy, have not been demonstrated so far in the IBD population, which tend to be a bit younger and have less comorbidities and risk factors for extraintestinal malignancies.

Other important side effects of JAK inhibitors include venous thromboembolism and venous thrombosis, which again occurred more frequently in patients exposed to tofacitinib and upadacitinib in trials. In particular, it's important for us, as clinicians, to differentiate the risks of blood clots due to active ulcerative colitis versus the risk of clot due to drug. But this is very important to keep in mind, in particular for patients who may have predisposition to thromboembolism and venous thrombosis.

In summary, JAK inhibitors are a new and growing mechanism in our field that are very effective and likely to be very effective in patients who are refractory to multiple agents. Currently just approved in ulcerative colitis and looking forward hopefully soon to approval in Crohn's disease as well. Thank you.

--