Key Factors in Assessing Disease Severity in Patients With UC

In this podcast, Baldeep Pabla, MD, talks about the different ways clinicians can assess disease severity in patients with ulcerative colitis (UC), including the use of biomarkers and technology, and discusses what is next for research in UC severity assessment. 

For more ulcerative colitis content, visit the Resource Center. 

Additional Resource: 

• Pabla BS, Schwartz DA. Assessing severity of disease in patients with ulcerative colitis. Gastroenterol Clin North Am. 2020;49(4): 671-688. doi:10.1016/j.gtc.2020.08.003.

Baldeep Pabla, MD, is an assistant professor at Vanderbilt University Medical Center, and a gastroenterologist at the Vanderbilt University Inflammatory Bowel Disease Center (Nashville, TN).

TRANSCRIPTION:

Jessica Ganga: Hello, everyone. And welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Ganga, with Consultant360, a multidisciplinary medical information network.

In the United States, about 600,000 to 900,000 people are diagnosed with ulcerative colitis, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Here to speak with us today about how to assess the severity of ulcerative colitis (UC) in patients is Dr Baldeep Pabla, assistant professor at Vanderbilt University Medical Center, and a gastroenterologist at the Vanderbilt University Inflammatory Bowel Disease Center in Nashville, Tennessee.

Thank you for speaking with us today, Dr Pabla. Please provide an overview of your article "Assessing Severity of Disease in Patients With Ulcerative Colitis."

Dr. Baldeep Pabla: Yeah. Thank you for having me on. This article provides both a historical context for how ulcerative colitis disease activity and severity were initially conceived and developed, as well as modern definitions of these 2 overlapping domains. We discuss clinical and endoscopic scoring tools, biomarkers, guidelines regarding treat-to-target therapy, and really try to focus on what's relevant to the practicing gastroenterologists when considering all these different aspects.

Dr Pabla: There's also a section that focuses on the inpatient treatment of patients who present with acute severe ulcerative colitis, which is a very important subtype of patients with ulcerative colitis in a population where there's a lot needed to standardize care across practices and to really improve our outcomes for these patients.

JG: When assessing disease severity, what key factors should clinicians consider?

Dr Pabla: So clinicians should be aware of these 2 overlapping, but different concepts of disease activity and disease severity. Activity is a snapshot in time for how a patient is doing and how active their disease is, while severity is a more encompassing term which considers historical factors regarding a patient's disease.

The ulcerative colitis overall disease severity index provides the clinician with a guidepost for how historical factors are important when you're asking your patient about what symptoms they've had and what complications they've already had, and assessing them and their disease in the moment that you're seeing them. And they help you to understand what cumulative bowel damage may have already occurred when you're seeing the patient and trying to assess what to do for that patient in that moment.

JG: Great, thank you. Could you please talk about the different ways that clinicians can score disease severity in patients with ulcerative colitis, and how the score impacts how the patient should be managed?

Dr Pabla: Yeah. So for a long time, the Mayo Score and the Mayo Endoscopic Subscore were the standard of care in assessing disease activity. And these are still very important tools. The UCEIS [Ulcerative Colitis Endoscopic Index of Severity] score, a score that is talked about in the paper, has become more diffusely used and it provides a more granular description for endoscopic disease activity. We've actually adopted the UCEIS score as the primary method of scoring in our practice and I personally find it to be very valuable when comparing patient's disease activity over time. It provides a little bit more information than just the Mayo Endoscopic Subscore. Providers should really aim for a Mayo Endoscopic Subscore of zero or a UCEIS score of zero to one as their treatment targets. In the article, we talk about the STRIDE [Selecting Therapeutic Targets in Inflammatory Bowel Disease] guidelines. And since the article's publishing, there's been an updated STRIDE-II guideline, which lists both of these endoscopic scores as goals for therapy.

We also discuss quality of life and patient reported outcome scores in the article, with a broad overview of several different ones, as well as the ones we use in our practice. The STRIDE-II guidelines talk about a PRO-2 score, which includes two variables as a part of scoring. And that's a very useful patient reported outcome score that providers can use when assessing disease activity for their patients. And we should also acknowledge that a lot of these treatment targets are goals that have to take into consideration other concomitant disease states that patients may present with, such as overlapping irritable bowel syndrome or small intestinal bacterial overgrowth.

Dr Pabla: Other considerations regarding treatment targets, historical ... or histologic targets remain aspirational goals. I think it's really challenging to achieve histologic remission with our current therapies for ulcerative colitis. So while it's an important part of assessment in evolving disease paradigms and how we look at the disease, it's still an aspirational treatment target. And some other important point of care or biomarker goals include faecal calprotectin and transabdominal ultrasound, which is briefly reviewed in the article and is a technology that I use in my practice to assess disease activity noninvasively, in patients with ulcerative colitis.

JG: You just mentioned biomarkers. How can biomarkers help determine the severity of ulcerative colitis?

Dr Pabla: Yeah. So probably the two most common biomarkers that are used in ulcerative colitis are C-reactive protein and faecal calprotectin. C-reactive protein is a great biomarker when patients actually mount a CRP, when they have flares of their disease, with levels of over five milligrams per liter being abnormal. There are plenty of patients though that do not mount CRPs, and so it's more challenging to follow disease activity with them with a serum marker.

In those patients, faecal calprotectin can be helpful. This is a stool test marker for inflammation. And as we discuss in the paper, there are various cutoffs for when we think patients have more significant endoscopic disease with faecal calprotectin. So generally speaking, a level over 250 micrograms per is a decent cutoff when considering more significant disease activity. This isn't a biomarker, but I will also mention transabdominal ultrasound here. I think that that's an important technology. And we can talk a little bit more about that in noninvasively assessing disease activity.

JG: Yes. Can you elaborate on the use of transabdominal ultrasound in assessing severity of the disease?

Dr Pabla: Yeah. So this is, I think an exciting area of research in our field and a technology that's been used in Europe and in Canada. It's essentially a radiology quality ultrasound machine that you can have embedded in your clinic. Patient comes to your clinic, you scan them and you can assess disease activity right there at the point of care, without any bowel preparation or need for intravenous contrast. It's very sensitive for Mayo-2 disease or above.

More mild ulcerative colitis can be more subtle in looking at this technology, but it's important to get a point of care assessment to help patients understand their disease in real time. And really can be valuable when a patient's having a lot of symptoms, because you can figure out right then and there what the bowel is looking like, how much activity is present. And can make decisions right there in clinic to help treat that patient in the moment and improve their quality of life and their long term outcomes.

JG: What do you believe are the next steps in research?

Dr Pabla: Yeah. So this article has a section on the inpatient with acute severe UC and I think this is a subtype of ulcerative colitis that we have a lot of work to do in improving outcomes. So ongoing standardization of practices between institutions about how these patients are treated is important. We've developed a protocol at Vanderbilt when our patients come in with acute severe UC, regarding rapid escalation of rescue therapy if patients aren't responding to our standard therapy. And there's really exciting ongoing research in the uses of Janus kinase inhibitors in these patients with acute severe UC that, perhaps have failed other more traditional therapies like Infliximab as an outpatient. And hopefully this will lead to improved outcomes, both for the hospitalization and long term outcomes, reducing the rates of colectomy and long term morbidity in these patients.

I mentioned a little bit about transabdominal ultrasound. I'll just also say, that's being studied here as a part of routine clinical practice. And there are several abstracts at conferences that are being presented in articles that are looking at transabdominal ultrasound, not only in Crohn's disease, which is more traditionally where that technology was used, but also in ulcerative colitis and monitoring patients over time.

JG: So it sounds like there is a lot in this area in terms of research. Do you think there are any gaps that need to be addressed?

Dr Pabla: Yeah. So I think a big treatment gap in this area that I think is really interesting is in the acute severe ulcerative colitis patient. Just generally speaking, our medications for ulcerative colitis treatments are effective, but they're not nearly as effective as we would like. And so there's ongoing research too, regarding combination biologic therapy. There's a very provocative trial called the VEGA study looking at combination IL-23, anti-TNF blockade, Guselkumab and Golimumab.

Which, I think the preliminary data that was presented shows a clinical remission and response rates over 80%, which is excellent, and something that we haven't seen in other treatments for patients with UC. So I think that's a very interesting and evolving space. But we have work to do with overall treatment effectiveness for our different regimens. And really breaking through that treatment response threshold of 80% and ensuring our patients not only respond, but get into remission and stay into remission with our therapies.

JG: What are the overall take home messages from our conversation today?

Dr Pabla: I think what clinicians should be aware of is that assessing disease activity and severity is extremely important in helping our patients achieve favorable outcomes. You have to use validated tools. You have to see how those patients are changing over time. And really have targets that you're aiming for, and adjust your therapy when you're not meeting those targets.

I think it's really helpful for clinicians to understand the historical precedent from where these scoring paradigms originated from, understand the limitations of the more historical scoring scores. And then also, understand how they should be incorporating these into their practice in monitoring patients moving forward. And the article helped patients and providers achieve a framework to do that.

JG: Well, thank you so much, Dr Pabla. Is there anything that you would like to talk about that maybe we didn't cover?

Dr Pabla: I think we hit the major points. I think there's a lot of different scoring metrics out there for looking at patient reported outcomes, quality of life, disease activity. I think it can be a little bit overwhelming. And I think for the practicing clinician, what's important is that you pick validated metrics and that you follow them over time. And that you're listening to your patient and you're responding to treat either ongoing inflammation or overlapping disease states.

And so there's a lot of different scoring systems out there, but the article reviews the ones that I think are the highest yield and the ones that you can do in a reproducible manner. And so really just picking a couple, sticking with them and making sure that you're reacting to patients when they're not achieving durable remission or having ongoing symptoms is really important.

JG: Well, thank you, again. We definitely appreciate you taking time out of your day to speak with us.

Dr Pabla: My pleasure. Thank you for having me.