Therapeutic Optimization in Crohn's Disease - Episode 4
Marla Dubinsky, MD: Where we’re moving, and tying it back to disease severity, I’d like to talk a little bit about risk stratification or risk assessment. Typically, how we behaved as physicians and patients historically is very reactive. We had this reactive behavior where we waited for patients to complicate and progress with either strictures or fistulas and said, “Wow, you’ve got severe disease. You now have a complication.” And we would then say, “Well, maybe I need to treat you differently.” But to be honest, developing complications is the end game. We don’t have drugs that reverse scar tissue, for example, so that usually leads to surgery. Sometimes the fistulas can be managed with medications and antibiotics, but recurrent fistulas, for example, mean that the patient needs to be operated on.
What we figured out is that we were defining risk at the end. So, what we started figuring out is, are there ways that we can actually risk stratify patient at diagnosis? Are there tools or hints, a crystal ball in a sense, for a patient who presents uncomplicated, and we can say, “Well, you have certain characteristics, therefore I’m going to treat you differently.”
What this comes down to is trying to figure out what the best risk factors are. There are some tools that are being developed and some that have already been out there that actually say if you have, for example, a 16-year-old female who has small bowel and perianal disease, who’s positive for X number of markers we can measure in the blood, that we could actually, in a visual display tool in real time, put in all these variables, toggle them in, and show a visual of what the trajectory of the prognosis is.
This tool is called PROSPECT. This tool has been developed in both pediatrics and in adults, and we’re currently looking to see how does that impact patient and physician decision making. Will I make a change if I have something at diagnosis that will actually predict how a patient will behave? What that means is if you’re at a high risk of developing a stricture or fistula, we need to intervene early. We’re not waiting for a patient to complicate and then pull out the best therapy we have. So, this whole proactive approach and risk stratification, I think, is a game changing and transformative moment for Crohn’s disease.
And so, we’re really pushing to make this part of the narrative and to see whether or not patients are also interested in knowing how they’re going to be in 3 years. It’s hard, because you just want to get through the day. So, there’s that discrepancy or disparity between what the patient wants to do today, to just get through today, and what we are saying: “Well, we want to prevent you, in 3 years from now, from developing a complication that needs surgery.” It’s hard to reconcile 3 years when I’m in pain or I just want to get to work. These are the things that we need to start really studying and figuring out so we can get patients and physicians to define risk the same way.
Stephen B. Hanauer, MD: The reason that we’re now doing risk assessment in patients with Crohn’s disease is that we’ve realized the symptoms don’t really reflect the underlying biologic inflammatory activity. We need to look beyond symptoms to predict how a patient’s disease course will progress. We also know that Crohn’s disease almost inevitably progresses from an inflammatory aspect of the intestine to involve transmural complications, such as strictures that can lead to blockages and fistulas that are abnormal connections between the bowel and another organ or even the skin. What we are trying to identify in patients are those who are at greatest risk for a more rapid progression to the complications of strictures and fistula that result in hospitalizations and surgery. We’ve learned that factors beyond symptoms are important regarding that prognosis. These factors include age at diagnosis, how much of the gut is affected, and whether or not there are actually complications at the time of diagnosis, such as the presence of perianal fistula. Patients who smoke cigarettes have a bad prognosis. And then, finally, we’ve recognized that patients with deep ulcerations are more likely to progress to stricturing or fistula. These are the individuals whom we want to focus our most aggressive therapy on to prevent that progression and the need for hospitalizations and eventual surgeries.
We are hopeful that early identification of high-risk disease will impact on long-term outcomes. However, this is actually a hypothesis at the present time. We know that our conventional step-up approach to these individuals does not really affect the long-term outcomes. So, we are anticipating with our new, more effective therapies that often include biologics that we can impact, and actually halt, the progression of the disease.
Marla Dubinsky, MD: I think it’s important to understand that once a patient does complicate, there’s significant morbidity. It gets back to the discussion on how long you want to wait to define something that you could maybe prevent and to get that idea of, how can I prevent a complication? Because once complications occur, there’s surgery, there are hospitalizations, there’s weight loss, and there are implications, for example, for fertility and pregnancy. That’s something that I also deal with. A patient comes to me and says, “I want to get pregnant,” and our conversation is, “We need to get you better. We need to minimize morbidity. We need to get you to a point where you’re not sick during pregnancy, so you have a healthy pregnancy.”
This idea of “let’s be proactive to minimize morbidity and the complications that arise with advanced disease” means I need to treat you early, before a complication occurs. It ties back again to the whole discussion that Crohn’s disease is a progressive disease. You need to get on good therapy, and for those who will progress, you need to predict who will progress and intervene at that window of opportunity.
Transcript edited for clarity.