Selecting First-Line Treatments for CD


David Hudesman, MD, Miguel Regueiro, MD, and Maia Kayal, MD, offer first line treatment strategies for patients with Crohn’s Disease (CD).


David Hudesman, MD: Let’s dive a little deeper into Crohn disease. Miguel, a patient with moderate to severe Crohn comes to your office with no biological or small molecule therapy. What are the factors going through your head? What therapies are you considering to use in the first line?

Miguel Regueiro, MD: I’d break down Crohn into a few simple types. Do they have 1 segment of inflammation? Do they have ileum inflammation or colonic inflammation? Or do they have multiple skip areas? This includes upper GI [gastrointestinal] tract, colon, small bowel? The reason I say that is because the latter is more severe. I’ll come back to how I approach that. The other part is their perianal area. The anal rectal area is sometimes the deciding factor on what I start with. Do they have extensive perianal disease? Do they have fistula? Is it a patient who’s coming in with deep ulcers in the anal rectal area? Because if we don’t heal that, if we don’t get that early, then patients who need surgery often come in and say, “I don’t want an ostomy on the first visit.”

To answer your question, sometimes our safest medicines may not necessarily be the best medicines initially. In the patient with extensive Crohn disease or perianal disease, I’ll still use first-line infliximab and azathioprine. I’m still using combination therapy for that patient. Over time, if the patient responds—they have a remission, they’re doing well—we may back off the azathioprine and then decide on monotherapy infliximab. However, if it’s a patient with a moderately active Crohn segment of the ileum or colonic-only disease, and they’re not terribly sick and don’t have perianal fistula, then you open up your toolbox. For today’s purposes, it will be ustekinumab, risankizumab, and vedolizumab, which are non-anti–TNF [tumor necrosis factor] agents. We’re talking about Crohn disease, so the small molecules wouldn’t fall into our categories even for first-line therapy. That’s how I break it down: are they very sick? Then I’d pull out infliximab, azathioprine, or maybe adalimumab azathioprine. Or are they somebody with whom can use vedolizumab, ustekinumab, or risankizumab as a first-line agent? Then we get into infusions vs injections. What’s the patient preference?

David Hudesman, MD: Maia, your thoughts?

Maia Kayal, MD: Miguel’s points are clear and to the point. I’m hearing that we’re focusing on risk stratifying these patients early on when we’re deciding on the therapy. In a patient with moderate to severe disease, you’re taking those factors into account. I agree completely: the anal rectal exam is key. If a patient has perianal disease, then the best drug is going to be an anti-TNF agent with combination therapy. The truth is, we have many great options now. Our therapeutic armamentarium has expanded significantly over the last couple of years, but we haven’t made much progress at getting our patients into that durable remission. A lot of times, our first drug is our best chance. We have the best chance at efficacy in getting our patients into deep remission with the first drug. So I agree completely.

In my very severe patients, and those are the patients who have perianal fistulizing disease, internally penetrating disease, I agree 100% to start with an anti-TNF and a combination with an immunomodulator. You have 1 chance to get them better, and you want to maximize that first chance. Then you can have these conversations when they’re in deep remission about de-escalating therapy if they’re the right candidate. You can start by peeling off an immunomodulator and continuing a biologic, but it’s important to be aggressive up front because you have 1 chance to get this right and get them into remission.

David Hudesman, MD: I agree. For anything that worries me, whether it’s perianal fistulizing disease, multiple small bowel segments, or deep ulcerations, that’s when you go to the tried-and-true TNF or combo therapy. That’s where we have the best data.

Transcript edited for clarity.

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