Transcript: Miguel Regueiro, MD: You mentioned risk and, Jessica, as I transition to ask you the question, we see patients all the time, and we know in our heart of hearts when they come in they’re very severe. This is a patient who may need surgery or who should probably go on an early biologic. Then, there are other patients who may be in referral centers who we don't see as much initially but are not as severe. How would you risk stratify? I know the AGA [American Gastroenterological Association], the ACG [American College of Gastroenterology], and different organizations have put together risk profiles for who's going to need surgery and who's going to be that bad outcome that David mentioned. What are some of those risk factors from a practical standpoint? How do you look at these in making a decision about more aggressive therapy early?
Jessica R. Allegretti, MD, MPH: Yes, thanks. Thanks, David, for setting me up quite nicely here. As you mentioned, a lot of our societies have put together a lot of guidance to help practicing clinicians. Generally speaking, when you're sitting in the office with a patient, and perhaps this is a new diagnosis, somebody you are working up, you want to be thinking about whether this patient is set up to have a bad outcome because you want to be attentive to that and be able to address those concerns early with your treatment strategy. When we think about overall risk factors for potential bad outcomes or more severe disease, we're thinking about things that Marla was already discussing: early diagnosis. How young were they when they were first diagnosed? How young are they as they're coming to you? Do they have extensive disease on the work-up you've done? For ulcerative colitis, do they have pancolitis? Do they have significant bowel involvement in Crohn disease? Have they already required multiple courses of steroids by the time they're coming to see you? On endoscopic assessment, do they have deep ulceration? Do they have perianal disease? Are there signs of systemic inflammation like very high CRP [C-reactive protein] or ESRs [erythrocyte sedimentation rate] on your laboratory evaluations? Have they already had infectious complications like C. diff [clostridioides difficile] or CMV [cytomegalovirus]? Certainly, in our patients with Crohn disease, we worry about our stricturing and penetrating patients because we know that they're more likely to have worse outcomes.
The reason this is important is because, once you've been able to identify somebody who is high risk early, just as David was alluding to, you want to be aggressive with those patients. You want to put together a treat-to-target strategy for them because, as we now know, treating to clinical symptoms is not enough. You have to be setting defined objective goals: endoscopic healing, histologic markers, laboratory values. You want to be following targets very closely in these patients to ensure that you are achieving the outcomes that you set out because, if not, these patients are much more likely to have increased bowel damage, need for surgery, hospitalization, and disability, as David was just alluding to.
Miguel Regueiro, MD: You touched on some important themes: in ulcerative colitis, that younger onset, severe pancolitis, deep ulcers. That's one factor that we all see, whether it be Crohn disease or ulcerative colitis. Seeing deep ulcers on the initial colonoscopy is a factor that prognosticates a more severe pattern and will probably require surgery unless we do something early. As we move in a few minutes to our next topic about treatment, that's something that will guide what we do. Perianal disease, you mentioned; infection, CMV, C. diff, these are all factors.
Jessica, let me stay with you for a minute, and then we'll open up to the group. In terms of the extraintestinal manifestations [EIM], how do you look at those? How do those play a role in terms of prognosticating severity of disease and response to therapy? Tell us a little bit about EIMs, how you approach those, and what those are.
Jessica R. Allegretti, MD, MPH: Extraintestinal manifestations are essentially just that. They are extraintestinal manifestations of the disease, whether they directly link with bowel activity or not, depending on which EIM we're talking about. Things like skin manifestations, rashes, uveitis; PSC [primary sclerosing cholangitis] is considered an extraintestinal manifestation of IBD [inflammatory bowel disease] as well. These characteristics put patients in higher-risk categories, not only because they are more extensive signs of disease, but they can also be much more difficult to treat because sometimes our therapies are not directly targeted at treating those EIMs, so you have to work with the patient to come up with a therapy that will not just treat their underlying bowel inflammation, which sometimes treats the EIM, but not always. You do have to be mindful that, even with achieving good endoscopic and histologic remission in your patients, the EIMs are still present. You need to come up with a strategy to address those as well, and it can be quite challenging.
Transcript Edited for Clarity