Future Directions in the Management of Ulcerative Colitis


Drs. Maia Kayal and David P. Hudesman discuss their hopes and future directions in the treatment of patients with ulcerative colitis.

Maia Kayal, MD: The future of therapy for ulcerative colitis is really about precision medicine. Right now, we haven’t cracked the code about which drug is the best for which patient. We’re increasingly understanding that the inflammation in ulcerative colitis is driven by multiple pathways, not just one inflammatory pathway. As a result, medications are not a one-size-fits-all and do not work necessarily the same for all patients. We’re increasingly understanding how we can predict which patient will be a nonresponder to which drug. Unfortunately, we’re not quite there yet, but I think with the increase in precision medicine in the next 10 to 15 years we’ll be able to meet a patient, draw a blood test or a stool test, or take a tissue sample, and be able to analyze and understand the pathophysiology of their disease, as each patient is unique with respect to their disease mechanism. I believe the future of ulcerative colitis is in personalized therapy and more selective therapies. There are exciting updates in the future for more selective agents, for example, against the p14 subunit of IL-23 [interleukin-23], more selective agents against the beta-7 subunits. In addition, I think the future of ulcerative colitis is in novel modalities of administration. For example, there are exciting updates for vedolizumab, and that it may shift from an infusion-based therapy to subcutaneous injection-based therapy, offering our patients who are in remission on vedolizumab improved quality of life and less need to be tethered to an infusion center.

One of the most anticipated developments in the field of ulcerative colitis is the use of novel noninvasive methods of monitoring. This primarily includes intestinal ultrasound, as we’re increasingly understanding that ulcerative colitis has transmural features in addition to just mucosal futures. The use of intestinal ultrasound in adjunct with fecal calprotectin and C-reactive protein is an excellent way to monitor your patients in the clinic. It’s a point-of-care test that can be done without preparation, without fasting, and can yield answers within seconds. Intestinal ultrasound will not take the place of a colonoscopy but can be used to monitor a long therapy before a colonoscopy is needed.

For patients presenting with increased stool frequency, urgency, or rectal bleeding, the biggest take-home message is to work up the symptoms quickly. It is to not delay the care or the work-up of the symptoms. Starting with stool studies, laboratory markers, and a referral to gastroenterology, or if they’re already with gastroenterology, a referral for a colonoscopy, is key. We know that a delay to diagnosis can impact long-term outcomes and increase the need for surgery. Therefore, it is important to make the diagnosis early, start the right therapy early, and then get the patient on the path to better care. It is also important to focus on improvement of quality of life and making sure the patient has the right ancillary support. This may involve referral to nutrition, psychology, and social workers to ensure that the patient’s quality of life is excellent and has improved with the therapies available.

David P. Hudesman, MD: As I mentioned, it’s an exciting time where we’ve had multiple new therapies hit the market recently for ulcerative colitis. In the next 1 to 3 years, we’re going to see more therapy, IL-23 inhibitors for ulcerative colitis, which has not yet been FDA approved, and another S1P [sphingosine-1-phosphate ] receptor modulator. If you look at some of these phase 2 trials, the next drugs we’re looking at are some oral medications that have some similar mechanisms of action to our current therapies. They are easier for a patient to take. There are some early data looking at different microbiome therapies, although we must see if that pans out.

When we’re talking about the future of therapy, there have been some interesting data at recent conferences looking at combination biologics. There was one study called VEGA, and it was presented in abstract form. It combined an anti-TNF [tumor necrosis factor] agent, golimumab, with a selective IL-23 inhibitor, guselkumab. What it saw was that this combination therapy did better than either alone, especially when you’re looking at mucosal healing or endoscopic remission. I think these are more of the studies we need to see. As new agents come to the market, we’re not really pushing that ceiling. We’re not seeing significantly higher clinical response or clinical remission rates. We’re having more options for our patients, which is critically important. But if we use some of this combination therapy up front, we might be able to push those response and remission rates. Right now, if we are using combination therapy, it’s usually in our very refractory patients, or patients with extraintestinal manifestations. I think the other focus in the future for ulcerative colitis is that true multidisciplinary approach and taking care of the entire patient, so not just symptoms, but improving the patient’s quality of life.

Treat-to-target is an important concept and something we’ve been talking about now for the past few years. What that means is that we’re not only treating to symptoms, but we also want to heal on the inside or have endoscopic remission, and ultimately in certain cases, histologic remission or true mucosal healing, meaning that on biopsies everything looks perfect. That’s our ultimate goal, but I think it’s important to realize that those targets aren’t attainable for many of our patients. When seeing a patient in the office, you need to set the specific target for that patient. Meaning if you have somebody come in with severe disease who failed multiple medications, maybe complete mucosal healing or complete endoscopic remission isn’t going to be attainable. However, if it’s patient you could put into clinical remission with significant endoscopic improvement, that’s a good target, and that’s OK. To keep pushing or switching is probably not the right thing to do. Treat-to-target is extremely important. But again, the key thing is to set a specific target for a specific patient, and discuss that target with the patient, and discuss how you‘re going to monitor and adjust to reach that target.

I would say the key take-home messages for managing ulcerative colitis, first it’s important to define the extent and the severity of disease, so then you can pick the right therapy for the right patient. Also, it is extremely important to closely monitor the patient. You want to set your target, monitor closely, and continue to monitor less frequently when you hit that target. I think just important, if not most important, is discussing with the patient what their No. 1 concern is when they come into the office. A lot of times, again, we focus on how many times they go to the bathroom, how much pain they’re having. But their No. 1 concern might be, how could they travel for work in the next 6 months? Bringing that up in the conversation, and working with a multidisciplinary team to help reach those patients’ goals and your own personal provider goals, is extremely important.

Transcript Edited for Clarity

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