Treatment Selection for IBD: Important Considerations

Stephen Hanauer, MD: What do you think about when you are “stepping up your game?” There are several different options from our societies. They include steroids with immunomodulators. And I know you and I have different perspectives on the immunomodulators. TNF inhibitors with or without immunomodulators, ustekinumab with or without immunomodulators, vedolizumab with or without immunomodulators, and tofacitinib now for ulcerative colitis [UC]. We have several different options for our patients. How do you select from one or the other mechanistic agents?

Marla Dubinsky, MD: I’ll divide them up. We’ll talk about Crohn disease, for example, and basically anti-TNF, vedolizumab, or ustekinumab currently. For me, it goes back to mucosal healing. We talked about depth of ulcers. For me, someone who has predominate small bowel disease who is not just moderate in nature, meaning it’s significant, it’s a length that’s not just 10 cm but a significant length, has extraintestinal manifestations [EIMs], particularly arthropathies or a lot of skin manifestations, I will go with an anti-TNF. That becomes my go-to. It doesn’t have to be infliximab; it could be adalimumab. Those are the 2 choices I would make. If it’s more scattered aphthae in the colon, or there’s a family history, or they themselves have had psoriasis, I’ll be honest, I will consider an IL-12/23 [interleukin-12 and 23 inhibitor], I will consider ustekinumab in that vein, as well as I would consider ustekinumab for small bowel. I don’t want to make it sound like I don’t use that; I use that a lot. You just have to be selective in your patients. And to me, I have more confidence in the mucosal data with an anti-TNF for significant small bowel inflammation. That’s my personal approach. If a patient has a more UC-like phenotype of their colon, then vedolizumab or ustekinumab gain traction in my practice. That’s how I think about Crohn disease. How do you think about those 3 in the context of location and depth of ulceration?

Stephen Hanauer, MD: I go by more depth of ulceration, frankly. I agree with you that the TNF inhibitors are probably the most effective for patients with more severe or deeper ulcerations. But many patients also present with a more moderate form, and in that situation, if there are multiple aphthae or little ulcers, we have the option of mechanisms such as ustekinumab, the IL-12/23 inhibitor, or even vedolizumab, particularly in the setting of ulcerative colitis. And we’ll get back to those distinctions perhaps in a bit. But you also mentioned these extraintestinal manifestations. And for instance, vedolizumab is considered more gut specific. Does that mean that you can’t use it in patients with any extraintestinal manifestation?

Marla Dubinsky, MD: Good question. There are 2 ways to look at EIMs. Are they parallel to the gut disease activity, or are they independent? That makes a big difference because as you get the disease under control and the erythema nodosum gets better, I’m using that as an example, it may not matter which therapy you’re using, as long as it’s in parallel to the gut disease activity. But there are others that are not related to gut disease activity that you do need to have beyond just gut selective. That would mean you’d go outside of, in this case, vedolizumab. I do want to note a distinction because people will also ask a lot about whether to use ustekinumab, because it’s approved for psoriatic arthritis, not rheumatoid arthritis. If a patient has true synovial inflammation, ustekinumab is not the right option, and you do need to go with an anti-TNF. That often gets confusing because people will think that ustekinumab would also be used for systemic disease. But there are certain systemic manifestations, and it’s not a classic rheumatoid arthritis. That’s where I think about dividing up, and there are some where, like pyoderma gangrenosum, I am going with an anti-TNF therapy, there is no discussion.

In my mind I am, again, judging severity at driving the speed at which I need it to happen, and the risk/benefit of not hitting it with the best therapy that we may have for that. I would also add that perianal disease obviously is one of the ones where you walk out of my room with the thought, in my opinion, that it earns infliximab. Anything that is beyond a simple fistula, I’m very much focused on treating it with the drugs for which we have clinical trial data, and we have a lot of adjustment and flexibility with dosing. I do like and prefer infliximab. Now, obviously there are data from post-hoc analysis in all these trials with much smaller numbers that there appeared to be some improvement with fistulas. Even in the most recent 5-year data for ustekinumab, there was a subset of patients for which there had been fistulas. But that does not mean it was formally tested in a clinical trial like infliximab was. I do take perianal disease very seriously.

Stephen Hanauer, MD: When I look at these extraintestinal manifestations, I’m thinking along the lines that you are, that there are several that are related to gut inflammation, such as the peripheral arthritis or even erythema nodosum. Whereas there are others that run this independent course. And you talked about more of a central arthritis, ankylosing spondylitis, sacroiliitis, uveitis, which are all HLA-B27 associated. Sclerosing cholangitis tends to run an independent course. I will treat patients who have, for instance, a peripheral arthritis that’s related to their disease activity. I may use vedolizumab as an option in those individuals. But one of the problems that I have is, how do I get a patient to a biologic quickly? This has been one of the things I’ve been really troubled by over the years because we virtually need to go through steroids to get a patient onto a more effective long-term approach. How are you dealing with steroids in your pediatric and adult populations?

Marla Dubinsky, MD: I’m going to distinguish Crohn disease from UC for a minute. In ulcerative colitis, if patients are having urgency rectal bleeding, up at night, steroids may be needed even in the acute setting no matter how quickly we’re going to a biologic. These are diseases that have a lot of symptomatic burden. With Crohn disease, on the other hand, we try to avoid steroids for growth reasons. Now, not to say that in UC there’s not a growth effect, but patients with Crohn disease already typically do have an impact on growth delay. Adding a corticosteroid doesn’t help the situation, and also, we can see quite a significant effect of using an anti-TNF with nutrition, for example. There are some patients who instead of corticosteroids for Crohn disease, we can use nutritional therapies as a bridge too, if patients are significantly malnourished and very growth stunted. We try to avoid corticosteroids in these situations. While we’re waiting for an anti-TNF, in case it doesn’t occur in a very rapid time of onset, we have other options in pediatrics that we are using as a bridge, for example.

Stephen Hanauer, MD: Such as nutritional therapy?

Marla Dubinsky, MD: Nutritional therapy.

Transcript Edited for Clarity