Considerations for Upfront Therapy in Crohn's Disease

William J. Sandborn, MD: As people think about the concept of early treatment, or treat-to-target, one of the issues that comes up is, how early in the disease course should highly effective therapies be used? I think for many of us, that becomes a risk stratification. We talked about that earlier in the program, that you really want to pick the patients who are low-risk and have mild to moderate disease, and those patients might be well-treated with a tapering course of steroids and careful observation. But about two-thirds of patients are more in the high-risk, moderate to severe category. They tend to have a progressive-destructive course that leads to complications of disease and fistula, stricture, abscess, and surgery. The only way to prevent those complications is to heal the bowel early, and the best way to heal the bowel early is to introduce a biologic, often in combination with an immunosuppressive, early in the course of disease. So, my personal thinking is to risk stratify the patients, and about two-thirds of the patients will need early combination therapy.

Marla Dubinsky, MD: I think what we’re beginning to see is that we are able to decide upfront that a patient has risk factors that will determine their prognosis to be at risk of a complication, especially patients with Crohn’s disease for perforations or stricture. Therefore, if we know that we have a select window of opportunity, we communicate with patients and say, “Look, this is what your risk looks like,” maybe through a visual tool and/or in communication, “and we feel that we could target your mucosa early.” We know that mucosal healing rates are much better if you don’t have bowel damage, obviously, so you get a bigger bang for your buck. You want to invest up front and be able to say, “I’m going to stratify you as someone who’s going to complicate; therefore, I want to give you the most effective therapy.”

In a patient who may not be a high-risk patient, which is not a lot of our patients with Crohn’s disease, you may be able to do somewhat of a step-up or accelerated step-up approach, or maybe nothing. Who’s to say that our treatments actually change the trajectory in patients who aren’t projected to complicate? That’s provocative in some way, what I’m saying, but the idea is that some of the future therapies, microbial based therapies or dietary interventions, may be OK for those patients who don’t complicate or aren’t predicted to.

When I have a patient in front of me who wants to use diet or some kind of complementary alternative medicine approach—because there’s much more on the internet about how dirty our medicines are and how unsafe they are, but how safe this tree bark or herbal diet is for Crohn’s disease, and it cured patient Mr X—of course they want to have control over the therapy. They read about these therapies. They’re worried about the safety of these therapies. Therefore, they want to hold on to this idea: Is there some kind of natural way I can control this inflammation? It could be in that small sample of patients who are not predicted to complicate that those are the patients in whom diet, or microbial or herbal or whatever therapy ends up being what it is, would be effective.

I no longer dismiss the idea that in some patients, there are nonclassic therapeutic approaches. Therefore, I work with patients and explain why risk stratification is important, which comes back to this idea of treatment needing to be tied to risk and getting patients to understand that their Crohn’s disease is different than maybe their aunt’s Crohn’s disease, or the first cousin of the first cousin’s Crohn’s disease. There are these large family trees that expand, and people integrate their experience and think that their Crohn’s disease may mimic someone’s who may be genetically related, but it’s not necessarily the case. The environmental trigger may be different. The microbiome may be different.

And so, trying to home in that it’s your Crohn’s disease and your personalized treatment plan helps us develop this communication and engagement and empowerment of patients to say, “I know what my disease is supposed to look like.” Even if I’m off by 10%, if I’m predicting it wrong by a little bit. It’s not quite an 80% chance of stricture, but it’s 68%. It’s still more than 50%, or it’s still more than 20%. I am developing that collaboration with the patient to help them understand that we are working together, we are both on the same page. We may come at it differently, but let’s meet in the middle.

That’s how you’re going to be able to go to the next step with patients, to really understand risk stratification with the patient, to make it personal and tailored and customized. This whole precision in IBD, the aspect of precisely and robustly monitoring a patient and diagnosing them and treating them. Being able to decide that this is a high-risk patient, and therefore, I’m going to go with this strategy—I may be overreacting, and the patient and I need to realize that this is what we have right now and we’re making our best guess at changing their life—I think that’s really where the treat-to-target comes in. We’ve been so focused on our targets that we haven’t asked the patient what their target is. And if we can somehow tie our target of mucosal healing to their target of having a normal quality of life and no disability, it’s a win-win for all stakeholders.

Transcript edited for clarity.