Transcript: Corey Siegel, MD, on Positioning JAK Inhibitors in IBD Management

Hi. I'm Corey Siegel from the Dartmouth‑Hitchcock Medical Center, where I'm the section chief of Gastroenterology and Hepatology and the codirector of the Inflammatory Bowel Disease Center. At the AIBD regionals in Boston, I'll be talking about positioning JAK inhibitors and emerging small molecules in IBD management.

The reason this has become so important recently is that there are many barriers to get therapy started early, particularly biologic therapies. You have to understand what those barriers are so that we can overcome them. In many cases, these barriers are concerns about safety, the ease of getting medications to your patients, and keeping your patients on these medications over time.

If we can make things easier for our patients so that they can get exposed to the right medications earlier in the course of the disease, then we really have a better chance of changing their disease outcomes. We can probably overcome many of these obstacles, but what we need are effective, safe, and easy-to-administer therapies for patients with IBD, which is where the small molecules come in.

There are a number of small molecules that are in development. There are probably over 20 of them being explored now for inflammatory bowel disease. Primarily, the ones that we've been talking about recently and the ones that are probably next up for us are the JAK inhibitors and the S1P receptor modulators.

The JAK inhibitors, you're familiar with one of them, which is tofacitinib, although there are a number that are already being explored and likely to come very soon to market to help our patients.

The S1P receptor modulators aren't quite there yet on the market for inflammatory bowel disease, but we did just get some topline phase 3 data on ozanimod, which is likely the first S1P receptor modulator that we will have available for our patients for ulcerative colitis.

The real benefit of these is they're very safe, they're easy to take, and we hope as effective as, or more effective than, the medications we've been using in the past. When you think about positioning and where to use them, it's really too early to understand exactly which small molecule to use and in what order. The promise is related to safety, ease of administration, and speed.

The considerations related to safety is making us think maybe we can move these up in the treatment algorithm. Could we even consider these for patients with mild to moderately active disease as opposed to patients with moderate to severely active disease? They haven't been studied for that mild to moderate patient population, but because of the safety and the ease of administration, it's something that we might have in our arsenal going forward for our patients.

The other thought about safety is can we start combining these drugs with other drugs such as biologic therapy? We're not there yet and this needs to be tested, but I think the exciting part about the future of IBD management is how we might combine therapies to really get on top of things early, get patients in remission, and keep them there. These medications do appear to work relatively quickly. Can we get them going and have efficacy fast, so we don't have to let our patients suffer or be exposed to corticosteroids either at all or for too long?

We need to go through a couple of questions with our patients when we're personalizing care. It's really thinking about how much individual risk is this patient of their disease, and how much does this individual patient have for risk related to treatment?

When we're thinking about urgency of onset of actions, is somebody teetering on hospital admission, or do we have a little more time to get them under control and get things sorted?

Then, of course, thinking about things like extraintestinal manifestations or which medications might help with symptoms outside of the GI tract? Are there particular safety concerns? Are these young male patients, or are they pregnant women, or they elderly patients? We have to think about that for choosing therapy. Does that patient have a preference to take oral medications vs intravenous infusions vs subcutaneous injections?

When we think about how these are going to be ordered and how we position these drugs, it's a little early to tell exactly where we put them. However, we know right now that the use of our biologic therapy is too low compared to the number of patients that we know experienced complications of their disease and get sick.

There's some barriers to overcome, again, around safety, efficacy, and ease of administration. If these small molecules are effective the way we think they are and are as safe as they appear to be, this will really give us an opportunity to consider using effective therapies earlier. Perhaps, even think about how we can combine these with other medications.

I hope that you find it interesting. We hope that you tuned in or watched further information at AIBD Regionals in Boston and future AIBD meetings in the future. Thank you.