Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And we have a panel for you today with Dr. Stephen Hanauer, he is the Clifford Joseph Barborka Professor of Medicine in the Division of Gastroenterology and Hepatology at Northwestern Medicine; and Dr. Parambir Dulai, he's an Associate Professor of Medicine in the Division of Gastroenterology at Northwestern Medicine.

In this episode, we dive into the world of inflammatory bowel diseases. Dr. Dulai and Dr. Hanauer share their current understanding of the causes of IBD, the potential complications and long-term effects of the disease, while sharing their current research aimed at the ultimate goal of curing the disease. Doctors, thank you so much for joining us today. And Dr. Hanauer, I'd like to start with you. Tell us a little bit about how you came to Northwestern Medicine.

Dr Stephen Hanauer: Well, I've been at Northwestern for approximately 10 years, approaching 10 years. I had been at the University of Chicago for over 35 years and rose through the ranks of the faculty to become the division chief there and helped develop an inflammatory bowel disease group and center at the University of Chicago. I was recruited over to Northwestern for really two basic purposes. The first was to help evolve, develop inflammatory bowel disease here. But equally important, as you're aware, Northwestern is expanding as a system and a healthcare system, and I was brought to help in the expansion of GI across the system.

Melanie Cole, MS: Dr. Dulai, what brought you to Northwestern Medicine?

Dr Parambir Dulai: Yeah. I came about two years ago. I moved from San Diego. I had done my training there and was on faculty at the University of California, San Diego. And I think the thing that really brought me here was the growth that Steve had talked about and the way that Northwestern has not only grown, but really integrated the system throughout its growth to make sure that it is one large academic health system and the research opportunities that came with that to start to think about personalization of care and really delivering care optimally for patients where they are, instead of having them come to us.

Dr Stephen Hanauer: And I have to say, I was prominent in the recruitment of Dr. Dulai for our IBD program, where he's already become an international leader. My comments about him is he really is IBD from soup to nuts. He looks at both population medicine, all the way down to cellular level, and you'll be interested in hearing about that.

Melanie Cole, MS: I certainly will. And Dr. Hanauer, I'd like you to speak about our current understanding of the causes of IBD because it's such a complex situation.

Dr Stephen Hanauer: Inflammatory bowel disease is much like other immune inflammatory diseases such as rheumatoid arthritis or psoriasis, multiple sclerosis. These are chronic inflammatory diseases which have components from genetics and from our environment. Part of our environment is actually the microbiome, the bacteria that live within us. And in probably different ways, they all contribute some proportion to the different types of inflammatory bowel disease, what we call phenotypes. So, some are driven more by genetics, some are driven more by environmental exposure, and others probably by changes in the microbiome.

Dr Parambir Dulai: Yeah. And just to add to that, I think our understanding has evolved with evolutions in technology, because you really only know what you can see. And as the technology has allowed us to see more with genetics and microbiome characterization and metabolism and cellular structure, we're beginning to know more and I think we're beginning to rethink how we sort of classify these patients and try to personalize some of it.

Melanie Cole, MS: That's a great point, Dr. Dulai. Thank you so much. And Dr. Hanauer, sticking with you for just a minute, what are the potential complications and long-term effects of IBD? How can patients and healthcare providers work together to minimize these risks with real shared decision-making?

Dr Stephen Hanauer: Well, inflammatory bowel disease, to the clinicians out in the community, know that it involves more than the intestine. And there are known what are known extra-intestinal complications: arthritis, skin inflammation and many metabolic complications as well. Liver diseases can be associated with IBD. So, as Dr. Dulai emphasizes, we really need to be comprehensive in how we approach these individuals. And that often requires teamwork, not only between gastroenterologists and our surgical counterparts, but also with our companions in rheumatology and in dermatology and other specialties so that we can co manage both the intestinal components as well as the extra-intestinal components.

Melanie Cole, MS: And we will get into the multidisciplinary approach a little bit later in our conversation. But Dr. Dulai, what are our current approaches to treating IBD with so many options in the toolbox now? Tell us about some of them and some of the challenges when deciding on these therapies.

Dr Parambir Dulai: Yeah. I think the opportunities have grown tremendously and, you know, fortunately we have Dr. Hanauer here who's seen that growth personally and been directly involved in that growth and leading that growth. We've gone from broad drugs that suppress the entire immune system, like prednisone and mercapturine and azathioprine to, progressively more selective biologics and small molecules, like the anti-TNF medications or drugs that block trafficking of immune cells to the gut. And that progressive selectivity and opportunity to personalize what we're targeting in the immune system has led to at least a dozen different therapies that we now have to choose from to really try to figure out what's most optimal for our patients. So, there's been a tremendous growth, not only in our breadth of opportunity for treatments, but also in the precision of the medications that we're using.

Melanie Cole, MS: There are so many options for treatment these days. And Dr. Hanauer, with all these options, what are some of the current gaps that you see in the treatment for ulcerative colitis and Crohn's disease? Tell us a little bit about where you think we could do just a little bit better.

Dr Stephen Hanauer: Well, we could actually do a lot better. We've advanced a great deal. And as Dr. Dulai pointed out, the biologic therapies, starting with TNF blockers, really changed the scenery for inflammatory bowel disease. And there have been many subsequent new developments, new pathways that are being interrupted. The problem is despite all of this, no single agent thus far has really made more than a 30 to 50% overall remission rate for our patients. So, that's a big gap where we really need to improve and to continue developing therapies or combining therapies in the future to try and close that gap.

Melanie Cole, MS: Well, one of the ways we're looking at, Dr. Dulai, is the IBD CDST. I'd like you to speak about how that works, some of the challenges in providing access for IBD CDST and how you've integrated this really into patient care. Speak a little bit about outcomes and what this is for other providers.

Dr Parambir Dulai: Yeah, absolutely. So, you know, as Dr. Hanauer mentioned, the plateau or ceiling of efficacy or benefit for these drugs that we're seeing is about 30 to 40%, and that's at the entire group level. However, when it works, it works 100%. So, what we thought was maybe we can find the patients who are more likely to benefit from one specific drug versus another, where we can increase that ceiling to 70, 80, maybe one day getting to 100% confidence that a drug is going to work for a patient.

So, the CDST can be found online. It's endorsed by the American Gastroenterology Association as an educational platform. What we did is we took all the clinical data that we had from the trials. We built different prediction models using very simple things that we sort of see and use in our clinical decision-making, labs, albumin, CRP, disease phenotype, and we were able to build a single-decision support tool that can actually help providers understand whether a patient sitting in front of them would benefit from an anti-TNF medication, a drug that blocks trafficking to the gut, or a drug that blocks IL-23 or some other mechanism that might be there.

And the great part about this is that we've seen a tremendous amount of uptake. Early on, we had some barriers with launching it, making it more accessible, getting providers to become aware of it. But since its launch in 2019, we've actually had tremendous growth. We have over 30,000 sessions this past year. And we're seeing it's a very easy-to-use point-of-care, and we're getting a lot of feedback that it really provides value not only for the provider, but also for the patient to feel more confident in the decision.

Dr Stephen Hanauer: Well, tell the audience, where do they find this clinical decision support tool?

Dr Parambir Dulai: Yeah. So, it's actually quite simple. You can find it at www.cdst4foribd.com. It's a free tool. You can use it whenever you need. There's a mobile version of it. You can use it in the clinic or before the clinic appointment. And we're actually increasing the opportunities for you to keep engaging through additional CME activities that you can pilot towards from going to the website.

Melanie Cole, MS: Such important work you're both doing. And Dr. Hanauer, please spend just a minute to tell us about the holistic model of care that recognizes the complexity of inflammatory bowel diseases. You spoke briefly about the importance of that multidisciplinary approach. I'd like you to expand on that and speak about the importance of this.

Dr Stephen Hanauer: Well, dealing with patients with inflammatory bowel disease does require a holistic approach. These are disorders that affect the digestive system. They are often accompanied by embarrassing symptoms or having surgeries that can impact on the cosmetics of the individual. It can affect children, their growth. It's a chronic disease. So in young individuals, they may take up a disproportionate amount of the family time caring for them. Likewise, as people age, it can affect their relationships, their jobs. Having diarrhea or bloody diarrhea or severe abdominal pain impacts on their work productivity and their life productivity.

And one of the aspects that we've learned is that the symptoms don't always correlate directly with the biologic disease activity. There are many kinds, many causes of abdominal pain that are not Crohn's disease. There are many causes of diarrhea that are not inflammatory bowel disease. And one of our jobs is to continually try to identify what are the aspects that are due to inflammation or what are the aspects that are due to the mind-gut connection as stress and other factors can certainly impact on intestinal symptoms.

Dr Parambir Dulai: Yeah. And I will just add to that and say that, you know, that was one of the big things about Northwestern's IBD program in particular that drew me here, is that they really look for everything. I mean, the fact that they're not treating just the inflammation or just one symptom and with the Gut Behavioral Program, the Dietary Intervention Program, the surgeons working together with the IBD physicians, it really does create an entire care team. And I think that's really what's needed to optimize it and it's been impressive to see that put together.

Melanie Cole, MS: Well, it's certainly an exciting time in your field, and we're learning so much more about that whole patient, that whole person approach. Dr. Dulai, how will your research help to transform treatment for both individual patients and populations of patients? As you speak about population medicine, tell us a little bit about your research.

Dr Parambir Dulai: Yeah. So, I think we started with the decision support tools as a broad compass to understand which patients might be better for certain drugs. But our lab is actually really getting into trying to discover new biomarkers and understandings of disease mechanisms. And we're now at a point where when a patient comes in for a colonoscopy, we can take that biopsy. We can look at millions of cells. We can look at the profile for those millions of cells and how they interact with each other and how that might contribute to response or non-response and eventually getting to the point where similar to oncology, where they run a test on the tissue. We might be able to run a test on tissue and biopsies and be able to confidently decide that an individual patient would benefit from a specific drug.

Melanie Cole, MS: That's so cool. And I'd love to give you each a chance for a final thought here. Dr. Dulai, what will it take to cure these disorders? Do you see a cure in the future? Give us a little blueprint for future research.

Dr Parambir Dulai: I think the primary goal is to get everybody under control. Once we figure out how to get people under control effectively and consistently, that's going to yield new insights into how to find how we can cure this disease, but I don't think we're that far off. I think progressively, as a field and as a group, we're moving in that direction, and that teamwork and collaboration is what it's going to take to really get us there.

Dr Stephen Hanauer: Inflammatory bowel disease is a chronic disease, as I emphasized in the beginning, and not that different than the majority of human ailments that are chronic, including high blood pressure, diabetes. I've already mentioned rheumatoid arthritis, psoriasis, et cetera. All of these require long-term treatment. We don't cure them at the moment, we control them. But they have many factors together. So when we talk about genetics, there are genetic contributors that are similar with inflammatory bowel disease and rheumatoid arthritis and psoriasis and such. There are environmental factors that are similar. Cigarette smoking can impact the immune system in many of these different diseases. Early childhood development, we've learned that there are four factors that can actually help prevent IBD in newborns to develop it. These include vaginal births, breastfeeding, avoidance of antibiotics, and also being raised with a furry pet. And these are contributions that are going to be important not only in IBD, but in other immune diseases. But as I said, in some diseases, in some individuals, genetics have a bigger component. So for instance, if an individual has inflammatory bowel disease, the likelihood is that only 2-3% of their family members might have it. If both parents have the disease, it goes up greatly in the children. So, we know that there are bigger contributions of individual components, and it may be breaking these down. So, some children who have a single gene that's malformed can be cured, actually, by a bone marrow transplant. But most of the patients have multiple genes affected. And so, that's going to take a much broader approach.

And I think one of the things our division is doing, led by Dr. Pandolfino, is the development of artificial intelligence for work at both the population level that Dr. Dulai is doing, and even down to his single cell research. AI is going to really accelerate advances along the way.

Melanie Cole, MS: Absolutely fascinating. Dr. Dulai, speak to other providers for just a minute. What would you like them to take away from this excellent conversation that we've had today and the IBD program at Northwestern Medicine?

Dr Parambir Dulai: I would say that you'd want to walk away with an understanding that IBD is a very debilitating disease with a huge impact to your patients that's often unseen. And asking and really understanding what you're looking for is very important. But there is a lot of hope, there are a lot of treatment options, and you want to approach it in a multidisciplinary manner. And I think the Northwestern Medicine IBD program really helps optimize that and get them there quickly. And I think we have everything under one umbrella to be able to put that together for the patient.

Dr Stephen Hanauer: IBD is a complex series of disorders. And it's going to take a great deal of unraveling, even at both the large scale, and the small scale that Dr. Dulai is working on. We've been able to recruit other investigators, including a leader in the field of the microbiome that's going to help accelerate our advances here at Northwestern, along with many of the clinical developments that Dr. Dulai and several of our other colleagues are working on.

Melanie Cole, MS: Thank you both so much. That was an absolutely fascinating conversation. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org. That wraps up this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.