Russell D. Cohen, MD - UChicago Medicine (2024)

I'm going to briefly talk to you about the next wave of new treatments in IBD. And when you see that little blue New Wave sign, that gives you an indication that this is something that is really new. Please note that Dr. Rubin and myself, we both do many different things, we are involved in research and consulting to many different companies. And my disclosures are here.

Just briefly, for those of you who aren't aware, when we talk about IBD, that's inflammatory bowel disease. A separate condition is called IBS, or irritable bowel syndrome, that's not what tonight's about, we're about IBD. Generally broken down into Crohn's disease and ulcerative colitis. Ulcerative colitis is just the colon, and Crohn's disease can be anywhere in the GI tract.

Sometimes we're not quite sure what you have, because sometimes your body changes. So, some people have an overlap, and we consider them indeterminate colitis. Although, many of them, we treat the exact same way.

So, the point to understand is that your immune system is supposed to protect you against infections-- It's your military. Your white blood cells, particularly, are your military. And what happens is that we think the immune system is attacking your own bowel.

So let's say, for example, you're this person here, with this colon here, and you get some type of infection or trigger from whatever it may be. And maybe it was a delicious tasting meal, but the person who it didn't wash their hands. Whatever it was-- Nevertheless, you get an inflamed gut. And for most people, most of the time, it gets better and you're on your own, and you're going off until you have your next bad meal.

But for patients with Crohn's and Colitis, there's a failure of the immune system to turn off the inflammation, and it keeps on perpetuating. And that's a very simple explanation of what we think is going on. And the reason why I'm telling you this is because, when we're going to talk about therapies, you'll have to understand that there's many different components of the immune system-- That are shown here on this slide. And this slide was made in 1997. And yet, the things that it hypothesized are actually the therapies that we're talking about today.

The very first advanced therapies were introduced 20 years ago-- Actually, in 1998. The biologics. Biologics were the biggest breakthrough in treating human diseases, not just inflammatory bowel disease. They're highly effective. They're much safer than the traditional steroids we used to-- And we still use sometimes some old immunosuppressants-- They're safer than that. And actually, if you use them early, patients get better quickly.

The way antibodies work-- this is, for example, anti-TNF antibodies-- is they block the white blood cell's receptors so the inflammatory protein, TNF, can't turn on the white blood cell. Because generally, your white blood cells are around just sleeping, and they only turn on when there's infection or inflammation.

So, the first of these breakthrough therapies were the TNF blockers. And many of you who have IBD, probably have heard of these and possibly are on them. Infliximab or Remicade, which now is available as biosimilars-- Inflectra, Renflexis, Avsola, and some others. Humira, Adalimumab, which will be available in biosimilars within the next year or two. Certolizumab, Cimzia and Golimumab, Simponi, they're all in the same family.

So, while they are slightly different medicines, they do work by the similar mechanism. These are relatively safe. There are some people who have serious events, but it's pretty uncommon. Most of the common rates of infections were the same as placebo in trials, but there are some infections. We had to make sure you don't have TB or hepatitis ahead of time.

And there are some very, very rare risks of certain types of cancers, that probably are more so from the immunosuppressants than the actual anti-TNFs. But they've been on the market for over 20 years, and we haven't had any major surprises since we started using them. The benefits far outweigh the risk in virtually all patients.

But if you had gone to some of our presentations-- Up until 2014, that's about it. We would talk about things, we would hypothesize, but we really didn't have another big breakthrough until 2014 . And the next new wave came, and that was a new class of biologics that were called the anti-adhesion molecule antibodies.

So, your white blood cells, which is shown over here, generally are in your bloodstream. And when they have to get into the tissue, the colon, to cause inflammation, they have to get out of the bloodstream by rolling along the wall of the blood vessel, and then squeezing their way through-- Just like that. And that's how the white blood cells get out of the bloodstream into the tissue.

Well, the way these drugs work is they block the white blood cells from doing that. So, they can't get out of the bloodstream. They don't go into the tissue. The nice thing is, is that scientists have figured out how to only block the white blood cells in the gut, and not everywhere else in the body. So, these actually aren't true immunosuppressants. They only prevent inflammation in the gut.

The one that's currently available for both Crohn's disease and Ulcerative colitis is Vedolizumab, Entyvio. Some of you may have, years ago, for Crohn's, been on Natalizumab, Tysabri. But Vedolizumab is the one that we use today.

Vedolizumab is exceptionally safe. We're not aware of any serious issues, unless you're allergic to it or have some type of strange reaction. There's no known infection risk. There's no known cancer risk. So, the benefits far outweigh the risks in virtually all patients. And this often is then the go to drug for older patients who we are a little cautious about some of the other agents, and even some patients who may be on other immune suppressing therapies.

But here's the new wave. We're looking to see whether Etrolizumab, a similar medicine, will make it out in the market. This blocks some of the same things that the Vedolizumab blocks, the Entyvio-- And also a new protein, which is somewhat related, to keep the white blood cells from attacking the bowel.

The clinical trials for Etrolizumab had some mixed results, they were positive in Crohn's and almost positive in Ulcerative colitis. So, we're going to see what's going to happen-- If this will make it out to the market pretty soon.

A similar approach is blocking something called MadCAM. So, MadCAM sounds like something out of Alice in Wonderland. But the MadCAM molecule, similar to what we talked about, is to prevent the white blood cells from getting out of the bloodstream and into the gut. And that's undergoing clinical trials. And it looked a little better in Ulcerative colitis than in Crohn's. So, it's kind of interesting how one could look a little better in Crohn's, and one a little better in Ulcerative colitis. We'll see.

So, 2014, Dr. Rubin and I were very happy. We were saying, Oh, we have a new breakthrough. And then 2016 came the next new class. So, a new therapy, and completely different than anything we had before. And this was a medicine that blocked two inflammatory proteins.

One was called IL-12, or Interleukin-12, and one was called IL-23. You may notice, they both have this blue unit, the p40 unit. That's actually what the drug is targeting-- The anti-p40. And that prevents the white blood cells here, from getting activated and producing inflammatory proteins. This is the drug that you see on the market that's called Stelara, or Ustekinumab.

Ustekinumab is also very safe. Very few people have any serious safety issues. The infection risk was the same as placebo in the clinical trials. Very rare to see any serious infection, almost unheard of. There's no known cancer risk. So again, the benefits far outweigh the risk in the majority of patients.

So, the new wave are going to be similar medicines. They actually block the other side, on the IL-23 compound, the p19. And these medicines are already on the market for psoriasis. And we're most likely going to see them come out in the market within the next few years for patients with inflammatory bowel disease. They are very, very safe. And that's one of the things that helps drive along the trials, because of the safety, and looks like they work. They certainly work very well in psoriasis. Very exciting.

So, only one year then elapsed before the next big wave came. And this was a new wave in many ways because it really wasn't a biologic-- This was going back to pills. So, before we had the biologics, everything was pills. And patients would say to us, Oh, I don't want to take all these pills, can't I just take a shot or IV once a month, once every two months, every couple of weeks. And we're like, sure, here, we give it to you. Now they're like, let me go back to the pills. OK.

So, there are the new class of pills that are called novel small molecules. I think they call them novel because that way, they can charge more for them. But nevertheless, they are novel, they are amazing breakthroughs in treating many different conditions.

In our condition, there's one product on the market right now-- They're called JAK inhibitors. So, JAK inhibitors prevent the white blood cells, which are here, from being turned on once the tumor necrosis factor, or the IL-12, or the IL-23, let's say the inflammatory protein, gets through the defenses and tries to turn on the white blood cell. This prevents the white blood cell from being turned on, so it doesn't attack the body.

And the therapy that's currently on the market for ulcerative colitis is Tofacitinib, or Xeljanz. The data in Crohn's wasn't strong enough to get approval, but we have been using it in ulcerative colitis patients. And it's a pill taken twice a day, and then there's an extended release once a day.

Now, since this is a pill, it is an immunosuppressant. So, while it's true that very few people have serious safety issues, we do have to be careful about infections. One of the things that surprised us was there are a higher rate of shingles.

So, if you have not had a chicken pox vaccine-- So, if you're probably under the age of maybe 27 or so now, and you never got the chickenpox vaccine, you should get the Shingrex vaccine. If you're 50 years or older, you should get Shingrex. And if you're younger and on immunosuppressants, you should get Shingrex. You cannot catch the shingles from Shingrex.

We're looking at studies about whether there might be a slight increased risk of skin cancer on this medicine. It's not clear just yet. The cholesterol goes up slightly, it usually doesn't mean anything. If someone has had blood clots or heart disease, we avoid it. And we avoid it in older people, unless they are completely healthy. But for most people, the benefits do outweigh the risks.

And there's a new wave of these medicines. A few other JAK inhibitors are already on the market for rheumatoid arthritis. Upadacitinib-- Or Upa, as we call it, which sounds like something out of a Willy Wonka movie. But Upa is not only on the market for rheumatoid arthritis, but moving through clinical trials in both Crohn's disease and Ulcerative colitis. And that will probably be the next one out of this group that makes it out.

So, if Dr. Rubin and I were doing this conference before-- What was it? May 17, or May 18 or so. We would be done. But we just had another new drug approved. This is exciting guys. And it's also a pill, so it's called a novel small molecule.

And this is an S1P inhibitor-- Or S1T modulator, actually. S1P stands for Sphingosine -1- phosphate. And that's why we call it S1P, because we can't say all that. And I mentioned the white blood cells in the blood. Well, the white blood cells actually don't live in the bloodstream, they live in the lymph nodes. That's what lymph nodes are for.

And then when the white blood cells get a signal-- it's like a military camp, that they should start coming out to figure out why there's infection or inflammation-- they have to get out of the lymph node. Well, this pill medicine prevents them from getting out of the lymph node, so they don't get out.

And this is a big breakthrough in MS, multiple sclerosis. And we finally just got the first of these drugs approved in ulcerative colitis, called Ozanimod, or Zeposia. It's also great because you can ask-- If you're going to take the medicine, you say, I Zepos so. It's bad, I know. Dr. Rubin's rolling right now.

There are very, very few safety issues we're aware of. If you have known heart block, you shouldn't take it. If you're wondering if you have heart block, you probably don't, because you'd know if you do. If you've had issues with uveitis or macular edema of the eye, we just have you see an ophthalmologist ahead of time. We're not aware of any major infection risk or cancer risk at this time.

And there's a new wave in this family. Etrasimod is moving to the clinical trials. This is a little more selective, in some ways, than the Ozanimod. So, that may make it better and safer-- It may not. The data looks pretty good so far. So, I'm looking forward on getting this out too.

There are many other things that we could talk about tonight. Psoriasis-- I mentioned, Ustekinumab is on the market for that. Well, this is a pill on the market for psoriasis called Apremilast, or Otezla. It does actually have some activity of IBD. Some people get diarrhea from it, so we have to be a little cautious with that.

And there's a whole bunch of other therapies that we're looking at. Patients with Crohn's fistulas, we're injecting stem cells into them, into the fistulas-- The surgeons do that. There's E coli, a bacterial inhibitor. There's other inflammatory blockers. Oral forms of Vedolizumab approach. Therapies we add on. This is a P-selectin glycoprotein ligand-1. That's what the bumper sticker on Dr. Rubin's car says, in case you want to know what that means. And eubacterial spores. Maybe there's something in nature that we can use to naturally treat the colitis.

We have tried and failed with some other interesting approaches, including the pig whipworm. So, you can rest assured now, the pig whipworm will not be in the next office visit with Dr. Rubin. There's been some theories for years that we're really missing a bacteria like TB that's causing the problem. It's unlikely to be true.

And we have done fecal transplants in inflammatory bowel disease. Dr. Rubin actually was able to get from the FDA an indication to do it for ulcerative colitis. We're wondering about the use of true feces in people, giving transmission of possible viruses and other conditions.

So, why do we care about all these different approaches? Well, the way that it's worked for many years is, we had one type of medicine and we just gave it to everybody. And we said, well, we'll see if it works, we'll see if it doesn't work. But wouldn't it be nice-- and this is just a pill formulation-- if maybe this guy did need a pill, and she needed a half a pill, and this person needs two pills, and this one needed a completely different approach.

So, what we're hoping to do-- and we're actually getting there-- and that's going back to the research, is identifying the predominant inflammatory pathway in each patient. Maybe we'll do a blood test, a stool test, a saliva test. And then we'll know what's the best one, the one most likely to work for you or for the patient. And then we can verify that that's working. And if it turns out that it's not working at all, we can now change to a completely different pathway. It's very exciting. We couldn't really do this-- Up to 2014, we really only had one pathway.

So, I always do this pitch. We need more people for clinical trials. Every therapy that's on the market is there because patients, perhaps like you-- If you're a patient watching, or family member, volunteer to do that. Please consider doing so. We have a huge clinical trials effort, and we're trying to make breakthroughs.

And again, I showed this picture before. At this point, I'm going to thank you for joining me for this first part of the presentation. And I'm going to roll this over now to Dr. Rubin, who's going to bring up the second part of the presentation.

Russell D. Cohen, MD - UChicago Medicine (2024)


Is UChicago Medicine the same as the University of Chicago? ›

A not-for-profit, academic medical health system, UChicago Medicine includes the University of Chicago Medical Center in Hyde Park, the Pritzker School of Medicine, the Biological Sciences Division, and Ingalls Memorial, a community-based hospital and outpatient facility in suburban Harvey.

What is UChicago medicine known for? ›

Of the more than 4,500 hospitals evaluated nationwide, the University of Chicago Medical Center ranked in the following specialties: Cancer, 14. Cardiology and heart surgery, 44. Diabetes and endocrinology, 17.

What hospital is affiliated with the University of Chicago? ›

Primary medical facilities on campus include the Center for Care and Discovery, Bernard A. Mitchell Hospital, and Comer Children's Hospital. Hyde Park, South Side of Chicago, Illinois, U.S.

Why UChicago Med? ›

Mission-Driven. Our students say our academic and research reputation, the quality of our faculty, and the success of our graduates all influenced their decision to choose Pritzker for their medical education.

Is UChicago better than Johns Hopkins? ›

In the 2023 Times Higher Education World University Rankings, JHU is ranked 15th out of 1,502 universities globally. University of Chicago has been ranked among one of the best colleges globally by some top-ranking agencies such as WS World Rankings, US News, Times Higher Education, etc.

Is UChicago Med good? ›

University of Chicago (Pritzker) 2023-2024 Rankings

18 (tie) in Best Medical Schools: Research and No. 61 (tie) in Best Medical Schools: Primary Care. Schools are ranked according to their performance across a set of widely accepted indicators of excellence.

Is UChicago Medicine a credible source? ›

We are fully accredited by the Joint Commission, the nation's leading organization for accreditation and certification of health care organizations.

What percent of UChicago students get into med school? ›

Though roughly 125 UChicago students apply to med school each year, those applicants have an acceptance rate of 75.2%, which is nearly double the national average.

Is Chicago Medical School hard to get into? ›

Current 2nd year med student there. The answer is yes, it's hard to get into. 250 of us across 3 campuses out of 9000 applicants the year I got in.

Who owns UChicago Medicine? ›

The University of Chicago Medicine, dating to 1927, is a not-for-profit academic healthcare system owned by the University of Chicago in Chicago, IL, with hospitals and dozens of outpatient clinics throughout Chicago and its suburbs.

What hospital is Chicago Med filmed at? ›

While the inspiring locale for Gaffney Medical Center is Chicago's Rush University Medical Center, the majority of filming takes place at Cinespace Film Studios. "We have three separate permanent medical sets on three stages," Delone explained.

Is UChicago Medicine a Level 1 trauma center? ›

The University of Chicago Medicine is designated as a Level 1 Adult Trauma Center by the Illinois Department of Public Health.

Is UChicago more prestigious? ›

While the Ivy League designation often notes prestige, there are many highly ranked colleges that are not on the list above. The University of Chicago is not an Ivy League Institution but is certainly considered a top college. In fact, the University of Chicago is ranked higher than many Ivy League institutions.

Why is UChicago so unique? ›

With our expansive and thought-provoking Core Curriculum, the foundation of our liberal arts education, as well as an extensive selection of majors, minors and specializations, UChicago students are well-versed in many different subjects of study.

How big is UChicago medicine? ›

UChicago Medicine

Opened in 1983, the hospital is comprised of 824 beds and has the most technically advanced equipment available to help provide expert medical and surgical treatment.


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