Expert Perspectives on the Optimal Management of Inflammatory Bowel Disease - Episode 13

Therapies Under Investigation to Treat IBD

June 1, 2021
Stephen B. Hanauer, MD, Northwestern University Feinberg School of Medicine

,
Marla Dubinsky, MD, Icahn School of Medicine at Mount Sinai

Drs Marla Dubinsky and Stephen B. Hanauer react to newer therapies currently being explored for inflammatory bowel disease and discuss where each may fit into future therapeutic algorithms.

Stephen Hanauer, MD: What we haven’t discussed is where tofacitinib fits into your disease management in ulcerative colitis.

Marla Dubinsky, MD: Before the label got changed—as a reminder for everybody—tofacitinib was approved for use not having failed anything, meaning you had moderate to severe ulcerative colitis and you were eligible. You didn’t have to fail anything. Because of safety concerns in another population, not even in the IBD [inflammatory bowel disease] population that changed. You have to fail anti–TNF [tumor necrosis factor]. Historically, I would have used it differently. I would have used it as an alternative to anti-TNF in someone whom I need speed. It gets back to rapidity. That would have been the situation. In this situation, for me, the same rules apply: Someone is failing steroids. They’re sick. They may have never responded to anti-TNF. Whatever the reason, it is my go-to for speed. I’m not starting to throw ustekinumab or vedolizumab at someone who’s refractory to steroids. This isn’t the time for that. In my opinion, I need something with speed, and that speaks to where I put tofacitinib. Are you using it similarly?

Stephen Hanauer, MD: I am, because I’m very distressed by the FDA’s applying the population of older men with rheumatoid arthritis who have risk factors for cardiovascular disease, where we do see a signal for increased risk vs a TNF inhibitor. In contrast, in the studies with tofacitinib in ulcerative colitis in our patients tend to be younger, who don’t have those same risks. The risks for these cardiovascular or thromboembolic events were not increased compared with patients with placebo. I am much more liberal in my thinking about tofacitinib in ulcerative colitis because it does have the advantage of being an oral agent and does work relatively quickly. 

That brings us to several other drugs that are nearing FDA approval. They have several mechanisms. One is the interleukin-23 inhibitors that are nearing approval. A second class is the S1P agents that are lymphocyte-tracking inhibitors into the lymph nodes. As you’ve already mentioned, there are a number of new JAK inhibitors. What are you looking forward to in the next year or so with these therapies entering the IBD [irritable bowel disorder] marketplace?

Marla Dubinsky, MD: I’m excited about what’s going to happen over the next few years because since 1998, we have progressed. We have on average about 4 different classes that we can approach. Now I’m thinking about all these changes that are going to come out over the next 18 months to 2 years, depending on whether all phase 3 data pan out. Already, ozanimod which is the S1P receptor modulator that you mentioned, the plan or hope is that it’s actually going to be FDA approved in June. We’re already moving toward having a completely new class in ulcerative colitis, and it’s more like a trafficking concept, but it works differently through the lymph node and is selective. And then having JAK1 inhibition only, which is the next JAK inhibitor, we won’t know whether that translates and has the same safety profile. We still need to evaluate that because what you said about tofacitinib may apply to the next generation of JAK inhibitors, so we’ll have to follow that closely. Are we going to interpret the same?

Are we going to have the same black-box warnings? It may impact our ability to use these effective drugs—like you, I am extremely distraught at the application from a completely different patient population. These very effective therapies are not being used to their optimization. Patients will suffer if we’re not able to use them for fear of perceived safety in our population, whether it’s real or not. What I’m excited about is this IL-23 revolution, because there are many different pharma partners who are studying them. With risankizumab for example, we just saw the induction. We just saw the induction data, and they’re very exciting early on. All the same things we’re talking about—rapidity to onset, having a great safety profile. Who knows, as you get more selective in the JAK inhibitors and in this p40, which is ustekinumab and is blocking IL-12 and IL-23, as we take away the blockade of IL-12, are we even going to get better and more direct and selective and safer results? That’s what I’m looking forward to: seeing how our upgrades along the way are going to improve efficacy and safety.

Stephen Hanauer, MD: Thank you for watching this HCPLive® Peers & Perspectives®. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peers & Perspectives® and other great content right in your in-box. Thank you.

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