Dr Cohen reviews his presentation from the Crohn's & Colitis Congress 2021 about positioning novel small molecule therapies, including JAK inhibitors, in the treatment of inflammatory bowel disease.

Russell Cohen, MD, is a professor of medicine and director of the IBD Center at the University of Chicago in Chicago, Illinois.

Hi, I'm Dr. Russell Cohen, professor of medicine and director of the Inflammatory Bowel Disease Center at the University of Chicago. At this year's Crohn's & Colitis Congress, my lecture was on positioning tofacitinib and other JAK inhibitors and novel oral therapies for patients with inflammatory bowel disease.

Many of you will find that this lecture is helpful to you. What I am discussing are therapies that are currently available on the market, at least in the United States, rather than things that you might never see.

Most of the lecture that I have talks about the JAK inhibitors. That's because we already do have one of the JAK inhibitors, tofacitinib, on the market for patients with moderate to severe ulcerative colitis. It is also used for rheumatoid arthritis and other inflammatory conditions.

The success of tofacitinib has only been hindered by labeling changes that requires for you first to have your patient fail or be unable to receive an anti-TNF therapy.

The other problem with tofacitinib is that unfortunately the Crohn's disease trials did not meet success. The labeling is only for patients with ulcerative colitis. Nevertheless, it's a very effective therapy for induction and maintenance of remission in these patients, even those who have failed prior anti-TNF therapies.

It's important that tofacitinib as well as other JAK inhibitors are not used with other immunosuppressive agents. There are a couple of other JAK inhibitors currently on the market in the United States but not yet for inflammatory bowel disease.

Baricitinib has received much interest as a possible therapy in treating COVID-19 in addition to rheumatoid arthritis. However, there really is no high-level IBD data at the time of this recording. Upadacitinib, or, as we say, UPA, has gone through Phase II and is now in Phase III trials in both Crohn's disease and ulcerative colitis.

There is some promise with UPA, or upadacitinib, which is a selective JAK inhibitor. However, it's unclear whether the dose that's used in rheumatoid arthritis, 15 milligrams once a day, will be enough for patients with inflammatory bowel disease.

While some of the Phase II trials suggested 15 or 30 milligrams may be effective, the ongoing Phase III ulcerative colitis trial's looking at doses of 45 milligrams. Along with a higher dose, there may be higher safety issues, although those have not yet been seen.

The other family of interest that we're looking at are the S1P inhibitors, or the sphingosine-1-phosphate inhibitors, which are already on the market for multiple sclerosis.

Fingolimod was the first of these. Recently, ozanimod became available for the treatment of multiple sclerosis as well as moving through trials in patients with inflammatory bowel disease, particularly ulcerative colitis.

While it is still in clinical trials, recent promising results in the ozanimod trial suggested this may actually make it out for approval, at least in ulcerative colitis, potentially in Crohn's disease if the subsequent trials are effective.

One of the nice things about this agent is it is also an oral therapy. The safety seems to be very good, and you can use it in patients who have multiple sclerosis, for which it's already labeled. You may remember that many of our therapies in the anti-TNF family are not used in patients who also have multiple sclerosis due to possible worsening of disease.

The final family that has been available in psoriasis and going through trials in patients with inflammatory bowel disease are the antiphosphodiesterase-4 inhibitors. Apremilast is on the market for psoriasis and has been moving its way through trials, mostly for ulcerative colitis. This also is an oral agent. The safety seems to be very good. The only hindrance is that when patients first start therapy, they get some diarrhea, although if you ramp up the dose, and there is a dose pack to do that, it is usually limited.

The point I'm making today is that there are multiple small molecules, which are pill therapies, for patients with inflammatory bowel disease that are already on the market either for ulcerative colitis, in the case of tofacitinib, or in other inflammatory diseases that are already reaching Phase III trials in inflammatory bowel disease.

If you have a patient who has an FDA-approved indication for these therapies, such as multiple sclerosis or psoriasis or rheumatoid arthritis, you may consider using these therapies to cover their FDA-indicated therapy but also to cover their inflammatory bowel disease.

This is Dr. Russell Cohen from the University of Chicago. I'd like to thank the organizers of the congress for inviting me as a lecturer as well as for help in providing for this educational moment. Thank you so much.