David Rubin, MD, on the Top 10 Challenges in IBD
Dr Rubin reviews his take on the top 10 challenges in inflammatory bowel disease facing researchers and clinicians, from cost to the search for a cure.
David T. Rubin, MD, is the Joseph B Kirsner Professor In Medicine, chief of Gastroenterology, Hepatology, and Nutrition, and codirector of the Inflammatory Bowel Disease Center at the University of Chicago School of Medicine.
Dr Rubin reviews his take on the top 10 challenges in inflammatory bowel disease facing researchers and clinicians, from cost to the search for a cure.
David T. Rubin, MD, is the Joseph B Kirsner Professor In Medicine, chief of Gastroenterology, Hepatology, and Nutrition, and codirector of the Inflammatory Bowel Disease Center at the University of Chicago School of Medicine.
Hi, it's David Rubin from the University of Chicago. I'm the director of our inflammatory bowel disease center and I wanted to highlight for you my opinion about the top 10 challenges facing IBD in 2025 and certainly carrying us forward to the new year.
The first challenge is that we haven't cured IBD yet. And I want to emphasize that it's part of our goal in taking care of people with Crohn's disease and ulcerative colitis to ultimately identify the causes and develop cures. And I say that as a plural because I really do believe there are many different forms of IBD beyond Crohn's disease and ulcerative colitis. And to that point, in fact, we're working with the International Organization for the Study of IBD to reclassify IBD, which I think will be well on the way to helping us do this going into the future. It's a very important challenge, and I wanted to start with that one so that we all keep that in our focus and, of course, acknowledge that's what our patients want, too.
The second challenge we're facing is that IBD has truly become a global condition. It's rising all over the world, everywhere you choose to look for it, we're finding inflammatory bowel disease. And in developing parts of the world, we're seeing a rising incidence and along with that of course is a rising prevalence, because thankfully most people don't die from this condition, they live with it their whole life. But in developed areas of the world like North America and Western Europe, we certainly are seeing a steady incidence with an increasing prevalence related to an aging population as well as just a growing population. So recognizing that this is truly a global problem, we need to also think about how we address it globally. That means thinking about where we should be working to treat the disease as it's appearing and where we should study it as it's appearing, so we can learn perhaps what the causes of it may be in different parts of the world and then of course make the therapies that are available and effective in other parts similarly available in the developing parts of the world, too. To that end, International Organization for the Study of IBD is working on what's called an essential medicines list, which is defined by the World Health Organization and we're hopeful that that will address part of this challenge.
The third challenge in IBD in the modern era right now is that there remains a large gap in primary response to therapy and unfortunately, a large number of people who lose response or what we call secondary nonresponse. And of course, part of this is because we treat people after the disease has been present for a long time and has already caused complications, and part of it is just because our mechanism doesn't work in some patients, or after it's working, the body finds a collateral inflammatory pathway to go around what we're trying to target. One way that I've come to understand this and explain it to my patients is that the immune system of the gut is actually doing what it thinks it's supposed to do, which is to protect the host. And therefore, if we use a single targeted therapy, the body inevitably might find a different strategy to do what it thinks it's doing, which is to protect you. And therefore, I think that this is an ongoing challenge, one that we're trying to overcome with new mechanisms, but also combination strategies, and really treatment paradigms that may incorporate something like surgery earlier for patients with Crohn's to reset the disease and focus on the preventive nature of our therapies as opposed to trying to catch up when there's already been fibrosis or damage in other ways.
The fourth challenge is that there's a large disconnect between our patients and their expectations and what we as clinicians say to them or think we're saying to them. This has been studied in a variety of ways, usually in surveys, but the bottom line is that many patients who are living with Crohn's and Colitis are either living without the adequate empowerment of knowledge to know that they should expect complete remission—meaning that the symptoms of their inflammatory bowel are gone—and that it should be
sustained. That means uninterrupted. For a patient, that means no flares. For us, that means no progression of the disease and it means no complications. And unfortunately, the way we think about it and may communicate it is not always translating or a patient just doesn't even hear it because we don't tell them. So we need to raise our expectations, we need to communicate more effectively. And I think this is an ongoing challenge that also is related to how we communicate about the available treatment options. Too often all of our therapies are just lumped into a bucket that sounds like they're unsafe and not something somebody wants to be on, when in fact many of our new targeted therapies are extremely effective and safe. And of course we must always put this in the context of the risk of untreated and progressive disease. So I think that there's a lot more we can do to communicate more effectively, and to do that we should be working directly with our patients and their families.
The next goal is that we've made IBD management too complicated, or maybe I should say we haven't made it simpler. And the reality of this is that we have made progress with new therapies that are available, but it's not clear when we should use certain therapies and what sequence we should be prescribing and thinking about how to use them and therefore it's very difficult for even the most well-meaning clinician to stay up to date and to have thoughts about when to use these treatments. I think this is a really important priority for us that we should continue to work to identify therapeutic biomarkers that will guide us in choosing therapy, so-called precision medicine, but in the absence of that, because we don't have that yet, we should be continuing to emphasize personalized approaches. Understanding phenotype, thinking about concomitant extraintestinal manifestations, and really focus on primary messaging about achieving the goals, regardless of what treatments we work through to get there. I think this is a really important message. It's one that we need to work really hard on in the new year.
The next challenge that exists in IBD is we don't really understand how to fully incorporate or maybe we're just not fully incorporating diet into management like we should. Of course what people eat affects their GI symptoms and of course what they eat or don't eat may have an impact on their disease status. But what we don't know how to do is how to proactively incorporate dietary strategies as an adjunctive, complementary, or even primary treatment for many patients with IBD. We certainly are accumulating more information. I want to remind everyone that eating and being able to socialize around food, which is how we do much of what we do to celebrate and to live, is quality of life. And so we're trying to figure out how do you provide people with good quality of life and education and knowledge and evidence-based choices about the food they eat and how it can or cannot affect their symptoms in combination with making sure we control the disease process. And there's emerging data and ongoing evidence that we're accumulating to help guide us in this regard but we need to work on that more and that's one of our big challenges.
The seventh challenge is that we have been unable to successfully recruit into many of
our clinical trials. Now you may think that that doesn't sound consistent with the fact that we have all of our new treatments but the reality is that we haven't been able to recruit in places like the United States and other parts of the Western Europe with our new therapies because we have available many therapies, because people don't want to have a chance of being randomized to placebo, and there are a variety of other exclusion criteria in very strictly designed trials. So recognizing that that's one of our big challenges, we need to continue to develop better study designs and think creatively about how to do more pragmatic research as well as look to the real world to gain evidence and have regulatory bodies like the FDA and the European Medicines Agency consider real-world data to help inform how we get therapies through and how we advance labeling as well. So this is an ongoing challenge that I think is really important. We also need more trials that are combo therapies and head-to-head that are not dictated by a single pharmaceutical company that happens to own both assets, but rather rational combinations looking at mechanisms that will make sense from a scientific point of view, and benefit our patients.
The next challenge is that we can’t afford IBD. And I include this in all my goals now, that we want affordable care—that’s affordable to the individual but also affordable to society. I understand why payers try to restrict access. That doesn't mean I condone it, but I understand it. It's because IBD has become so expensive. It's estimated that advanced therapies for IBD will be a $30 billion industry in the U S in the next 10 years. And we should acknowledge that that's not an affordable strategy in a disease that's chronic like this. We need to be thinking about how do we do things more cost-effectively. And that requires the challenge of embracing such things as early surgery with more effective prevention and better studies of cost-effectiveness so we understand. It also means embracing less expensive options like biosimilars for some strategies, but knowing how they work and what that means and still having economy in terms of the decision-making process is critically important as well. So recognizing how expensive these diseases are, that's why it's one of the main challenges that I've highlighted.
And then the next challenge, the ninth challenge, is that we need to focus more on prevention altogether. One of the first things I want to remind everyone is that maintenance for Crohn's disease and ulcerative colitis. maintenance of remission is about preventing relapse and preventing progression. Too often people think maintenance therapy is about using active treatment for active disease. Chronically active disease is not maintenance of remission. That's ongoing treatment for active disease that hasn't been successfully induced into remission. Now that's the first part, but the other part is understanding how to prevent recurrence after surgery in Crohn's, how to prevent pouchitis in people who get J-pouches, and the increasing emphasis and understanding of identifying those who are at risk for developing IBD in the first place, and then developing ways to prevent it from progressing to a clinical disease. What does that mean? Family members of Crohn's patients who might have a risk of developing Crohn's themselves, especially siblings, and understanding some of the biomarkers that will predict subsequent inflammatory phenotypes or the manifestation of the clinical disease are high-risk groups that we might target for a safe and hopefully effective prevention strategy. And we're learning from our colleagues in diabetes and other areas how we might actually do this. So stay tuned, but that's a major area of interest and one of our big challenges.
And our last challenge, number 10, that I think is important for us to keep in mind is we need to continue to encourage and train our replacements—the young amazing people in our field and those who are coming up through the ranks, who are going to take the reins and bring us into the future in the way that we need and that our patients need. And I really think that's a priority that we should continue to focus on. These days with all the challenges in federal funding in the US, in getting grants, in getting therapies approved, and of course the lifestyle issues of working so hard to become professionals and become subspecialists in the field of IBD, are all disincentives for some people. So ongoing active and very intentional mentorship and career advising and grabbing those really talented young people who are all around us and bringing them into our space is one of our challenges that I personally look forward to continuing to work on as we enter the new year.
Thank you for your attention. I hope that you agreed with this. I would love to hear what other challenges you have in mind.
