Transcription:
Understanding Crohn's and Colitis - Part One

Melanie Cole (Host):  Welcome to Back to Health, your source for the latest in health, wellness and medical care, keeping you informed so you can make informed healthcare choices for yourself and your whole family. Back to Health features conversations about trending health topics and medical breakthroughs from our team of world-renowned physicians at Weill Cornell Medicine. I’m Melanie Cole and today I invite you to listen in as we discuss Crohn’s and Colitis Awareness. Joining me in this panel discussion is Dr. Dana Lukin. He’s the Clinical Director of Translational Research for the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medical Center. And Dr. Randy Longman. He’s the Director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medical Center. Gentlemen, I’m so glad to have you with us today. This is a really important topic and more people than ever are showing up with Crohn’s Disease and colitis. So, Dr. Longman, I’d like to start with you. Please define inflammatory bowel diseases for us. Explain what IBD is and how Crohn’s and colitis fit under this umbrella term.

Randy Longman, MD, PhD (Guest):  Thanks Melanie and thanks for having us on the program. It’s really important to raise awareness for inflammatory bowel disease and thank you for all that you’re doing. Inflammatory bowel disease as you mentioned, is an umbrella term that broadly describes chronic inflammatory disease that can affect the intestine. There are several different subtypes of inflammatory bowel disease. Those include Crohn’s Disease and ulcerative colitis. And patients may experience really a wide range of symptoms with this. They can be diarrhea, nausea, vomiting, abdominal pain, rectal bleeding; all of which can – they can really range from minor symptoms to more severe symptoms. 

And so, it’s really important to be able to recognize those symptoms and to speak with your doctor about evaluating those. 

Host:  Dr. Lukin, people have heard the term inflammatory bowel disease. They’ve also heard the term irritable bowel syndrome. They’re confused when it comes to these. Tell us the difference between that and why irritable bowel syndrome does not really fit into that inflammatory bowel diseases. 

Dana Lukin, MD, PhD, FACG (Guest):  So, that’s a great question and very commonly asked in clinical practice and in fact, we will frequently have referrals intended for IBS at the IBD Center. So, obviously the major similarity is the first two letters. And so, inflammatory bowel disease as Dr. Longman has just described to you involves inflammation which is an immune mediated process in the bowels associated with many of the similar symptoms like diarrhea, abdominal pain as you’ll see with irritable bowel syndrome. However, it’s clearly an inflammatory condition. Irritable bowel syndrome is what is sometimes referred to as a functional condition which is not due to inflammation in the bowel. So, whereas one of the major distinguishing features between the two will be the presence of bleeding and systemic symptoms including weightloss and some other major complications that are associated with inflammatory bowel disease do not tend to be present in irritable bowel syndrome. 

So, I think it’s important to think about how to distinguish the two using objective testing and also of course listening to our patients describe their symptoms and try to understand exactly which condition is applying to your patient. 

Dr. Longman:  Yeah and if I can just add to that, exactly as Dr. Lukin said, these are fundamentally different processes. However, they overlap. They can overlap in the same patient. The same patient can have inflammatory bowel disease and IBS. And so, sometimes when the inflammatory bowel disease can get under control with medicines, the patient can still suffer from irritability of the bowel symptoms. And so, that has to be distinguished exactly as Dr. Lukin said and so it’s really important to be able to distinguish the two because the medical therapy to treat those two things is completely different. And so it is very important to distinguish those two. 

Host:  What a great point Dr. Longman, that you made. So, what are the risk factors? Is there a strong genetic component for inflammatory bowel diseases? And what are some of the more serious complications of these because people really do have some complications if they’re not treated with some of these advanced therapies. So, tell us about the main risk factors and some of the complications that you’ve seen. 

Dr. Longman:  Yeah, perfect question. What we know and what we’ve known for many years, is that inflammatory bowel diseases and Crohn’s Disease and ulcerative colitis frequently travel in families. And taking a detailed family history is sort of the old way of doing genetics and figuring out the fact that there are specific genes that can drive the underlying disease of Crohn’s Disease and ulcerative colitis. Some of these genes are well known and well-described. And people with mutations in these genes can have more aggressive disease. What does that mean to have more aggressive disease? Sometimes people can develop complications associated with Crohn’s Disease; abscesses, fistula which is a communication between the intestine and another part of the body. And these are very complicated issues and can make the disease more difficult to treat. 

And so recognizing aggressive disease is important because it’s important to make sure that we start therapy quickly to address that. 

Dr. Lukin:  And I’d like to add to both parts of that question. Which is actually also a great question. So, I think with regards to risk factors, while genetics happen to be the most well-established risk factor for inflammatory bowel diseases, a lot of what causes IBD is unknown. And one clear risk factor for Crohn’s Disease is cigarette smoking and interestingly, this does not seem to be as strong a risk for ulcerative colitis. It’s thought that some other factors may play a role in triggering inflammatory bowel disease and that includes the factors in the Western diet including certain food additives and emulsifiers and other environmental exposures. 

I’ll add with regard to complications of inflammatory bowel disease. Randy mentioned several that are associated with Crohn’s Disease. The other risk factors that we – or the other complications associated with IBD include that especially for patients with inflammation involving the colon is dysplasia which is precancerous changes of the colon or progression to colon cancer. And that’s why it’s very important to screen our patients with involvement for several years to look for this very carefully. 

Host:  Dr. Lukin, I’m so glad that you mentioned just there triggers. Because we’re hearing more, and we’ll talk later about the role that diet plays because it is such a big part of living with Crohn’s or ulcerative colitis. But what about things like stress, because that has been something that’s been talked about. It’s been researched. Tell us what role stress plays as a trigger for either of these and any lifestyle you want to mention.

Dr. Lukin:  So, that’s another very frequent question from patients. And I think clearly stress affects the gut both in inflammatory as well as noninflammatory conditions. You’ve heard the phrases going back years and centuries; I have a nervous stomach; I have butterflies in my stomach and there’s a very intimate connection of the brain and the gut. So, stress is absolutely linked to exacerbations or what are typically referred to as flares of one’s inflammatory bowel disease. And this can be emotional stress. This can be busy times at work or school. Very frequently in our school aged patients, we will see around the time of exams, a major life transition, breakup or even a good life transition such as a wedding we’ll see patients with worsening symptoms. 

So, there definitely is a clear link with this. Now not all patients will experience this and I think it also like we were discussing in an earlier question, separating symptoms from actual inflammation is very important here because stress may trigger an increase in symptoms does not always mean that the underlying inflammation is worse and so trying to find ways to deal with those stressors effectively can help to minimize potentially the duration of flare type symptoms and also get patients moving forward and feeling better as quickly as possible. 

Dr. Longman:  And one thing that I’d like to add to it and Dr. Lukin that’s great. One thing that I would like to add to that is that sometimes these stressful conditions can unmask the fact that maybe the medical therapy is not optimized. Maybe we can do a better job at optimizing care to make sure that the inflammatory disease is even more quiet than it is. And so sometimes, when these stressful events are causing “flares” even if the patient feels that it’s kind of mild; it’s an important time to sort of reevaluate that and see whether or not things are optimized or whether or not we can get on a better medical regimen that will help things stay quiet. 

Host:  Dr. Longman, that’s a great point that you made, and I love that you used the word quiet. As we start now talking about the main goals of medical treatment for inflammatory bowel diseases; are they mainly to quiet the symptoms? Is it symptom management? What are some of these standard therapies you use? Tell us about some of the gamechangers, some of the most exciting advances in the field of inflammatory bowel diseases and what they’re really – for patients listening, that have loved ones as I do with these diseases; what are they intended to do?

Dr. Longman:  Yeah, that’s a really great point and it’s really been a focus of the clinical research that we ourselves at Cornell and others have been trying to address. Historically, the metrics that we’ve used are symptoms. How frequently are you going to the bathroom? Is there bleeding when you go to the bathroom? Our therapies are intended to reduce that and to improve the quality of life. Because that’s really what we’re going for, right, we want people to feel better. We want to enable people to enjoy their life and to not have active symptoms. 

And so historically, those are the things that we followed and those are things that we continue to track during visits, during video visit, during follow ups et cetera. However, the clinical research has shown, our own work has shown is that there are evolving blood tests, there are evolving stool tests that allow us to get a deeper understanding of how well we’re doing with this medical therapy. There are blood tests that can look at inflammation. There are blood tests that can look at the levels of a certain medicine in the blood. There are stool tests that can serve as a what we call a noninvasive surrogate, so not having to do an endoscopy but being able to understand how much inflammation is going on in the intestine. And these are really great tests because it gives you and your doctor the opportunity to understand how well you’re doing. 

Now, also with the improvement in endoscopy and availability of endoscopy, being able to look at the intestine and see visually whether or not it’s inflamed and to know with a biopsy whether or not it’s inflamed; that has turned out to be a really powerful metric in understanding the question how well are we doing. If there is what we call mucosal healing, if there is endoscopic improvement of the inflamed tissue, if there is histologic improvement, meaning the pathologist looks at the biopsy and says yup, this looks way better; that is very meaningful for how well we’re doing and how well we will continue to do on that medical therapy. And conversely, if there is a smidge of activity or evidence of inflammation coming back; that really gives us a hint that we need to escalate or change what we’re doing. 

Host:  Dr. Longman, expand a little bit for the listeners because we’ve heard about biologics and infusions and they hear about all of these things. Tell us a little bit, just a very brief description of some of the things that you’re using today.

Dr. Longman:  Yeah, absolutely. So, as you and many of the listeners are aware, there is a continually expanding arsenal of medical therapy to treat inflammatory bowel disease. One large class of medicine that has been used for gosh, 20 years plus now is targeting a protein called anti-TNF alpha and these are your medicines Remicade, Humira, Simponi. They come in many different forms. Some are IV infusions; some are injectable medicines. And these have really been a mainstay of biologic therapy. Excellent for Crohn’s Disease, excellent for ulcerative colitis and really excellent for complications that we talked about, fistulizing disease, perianal disease associated with Crohn’s Disease. These medicines are wonderful and not just for inflammatory bowel disease, for other inflammatory diseases including rheumatoid arthritis and other inflammatory diseases. 

Over the last five to ten years, and even more recently, we’ve added to that arsenal significantly. One is a medicine targeting integrins and most notably this is called vedolizumab or the trade name is called Entyvio. And this is a medicine that may work by blocking immune cells trafficking. This is an excellent medicine for ulcerative colitis and has been shown in recent studies to maybe even be more effective than some of the anti-TNF alpha medicines for the treatment of ulcerative colitis. It’s also approved for the use in Crohn’s Disease. 

Over the last now couple of years, a medicine called ustekinumab or Stelara which targets a different pathway called IL-1, IL-23 which was previously approved for psoriasis has now also gained approval for Crohn’s Disease. This is an excellent medicine. It’s given by IV and then followed every eight weeks or every four weeks by subcutaneous injection. This is notable because it’s a very safe medicine and so the safety profile of these newer medicines Stelara and Entyvio may even be more favorable than some of the older anti-TNF alpha medicines while still maintaining efficacy. And so now Stelara is approved for Crohn’s Disease. It’s also now approved for ulcerative colitis and could be a wonderful option. 

More recently, small molecules, so these are not biologics but they’re oral medicines that can inhibit a signaling pathway downstream of some of the cytokines or some of the proteins and molecules involved in inflammation. One that is notable is called Xeljanz or tofacitinib. And this medicine is approved for ulcerative colitis and can be very effective. There are some safety considerations and so, everyone obviously should be discussing the risks and benefits with their doctors. I’d also just like to say that there are many medicines, new medicines evolving with interesting mechanisms and maybe even improved safety profiles that are coming down the pike and so, I think that there’s a lot of enthusiasm for these types of therapies. 

Dr. Lukin:  I’d like to add that I think that was a great synopsis of a very complex topic Dr. Longman. And I think I agree, so the field is evolving from a very reactive approach where we used to treat to symptomatic remission and now towards deeper targets using what we call a treat to target approach and some of these newer molecules are able to treat the disease more systemically, more disease modifying fashion to prevent complications down the line. We’re seeing different mechanisms of delivery from pills in the beginning that were maybe topical or less systemic to now more focused mechanisms with these intravenous or subcutaneous deliveries and now again shifting back to more small molecules that are oral and so it’s really revolutionizing the field and we’re understanding now really, how we can use these in different sequences and maybe to target patients with different disease features. And so, it obviously while there’s more choices, makes it a much more complex decision making and I think it just underscores the real importance of having a great – a good relationship with your physician and care team as well as just making sure you as a patient, understand the disease process and what the options are. Because I think really having a team approach and an informed approach really helps make good decisions to treat the disease. 

Host: Thank you so much to our guests for all this great information. That concludes part one of our two part series on Crohn’s and Colitis Awareness. Please be sure to join us for part two. Do not miss the rest of this fascinating and informative interview of back to health with Weill Cornell Medicine. And while Weill Cornell Medicine continues to see patients in person as well as through video visits you can be confident of the safety of our appointments at Weill Cornell Medicine. We’d like to thank our listeners and invite our audience to download, subscribe, rate and review Back to Health on Apple podcasts, Spotify and Google Play Music. For more health tips please visit www.weillcornell.org and search podcasts. Parents, don’t forget to check out the Kid’s Healthcast. I’m Melanie Cole.