Dr Rubin recaps his address at Digestive Disease Week on positioning advanced therapies in IBD, emphasizing the importance of assessing disease activity, prognosis for complications, and using a treat to target approach to achieve and maintain remission.

David Rubin, MD, is the Joseph B Kirsner Professor In Medicine, chief of Gastroenterology, Hepatology and Nutrition, and director of the Inflammatory Bowel Disease Center at the University of Chicago School of Medicine.

TRANSCRIPT:

Hi, it's Dr. David Rubin from the University of Chicago. I'm at DDW 2024 in Washington, DC. This has been a great meeting so far with a lot of new science and a lot of discussions about how to take care of patients with inflammatory bowel disease in new and important ways. One of the lectures I was invited to deliver at this meeting in the postgraduate course was about positioning our advanced therapies for people with IBD. And I broke it down into 5 basic principles.

The first one is to make sure that we are adequately identifying the people who have the disease that needs an advanced therapy. Who are those patients? Whether it's Crohn's disease or ulcerative colitis, we certainly appreciate that the patients with more extensive bowel involvement, more endoscopic activity, laboratory abnormalities; in Crohn's disease, the person who's smoking cigarettes or who has perianal disease; and in both situations, patients who need steroids or who've been hospitalized for their condition or who've had infections already related to their condition. All of those patients should be on advanced therapies to manage their disease.

I also added some other considerations for who should be receiving advanced therapies. And that included patients who have extraintestinal manifestations, either related to their bowel or just a comorbid condition. I included people who had additional mental health challenges that might be compromising or affecting their ability to manage their disease or be a direct result of having the inflammation in their body, and I included a variety of other considerations.

In this presentation, I then defined what an advanced therapy is. Those are our monoclonal antibodies and now our novel synthetic small molecules. I also defined an advanced therapy as one that perhaps you are not prescribing because you're nervous or don't have a fund of knowledge yet to use it properly and that's a very important barrier to overcome.

The second major principle in this presentation was about making sure that we talk to our patients and communicate effectively about achieving remission: symptomatic remission, which means improvement in their quality of life and the absence of symptoms related to their disease; deep remission, which means that we pair symptom improvement with objective measures of disease control, endoscopy, laboratory values, stool tests, cross -sectional imaging, and increasingly, intestinal ultrasound; and then the third type of remission that we should be talking about and working towards is functional remission. This means that in addition to healing the bowel and improving symptoms, we have achieved a level of functional performance for our individual patients where they can go to school and go to work, raise their family, and do all the other things they want to do.

The third point I made in this presentation was to not wait for patients to earn their way up the ladder of therapies. When you know somebody has more advanced disease or has a prognosis for poor outcomes, we should be embracing our treatments earlier. There are an abundance of data now that show that earlier treatment of Crohn's disease with any of our therapies is more likely to achieve remission, less likely to lose response over time, and importantly, less likely to result in surgeries and hospitalizations and other adverse outcomes. In ulcerative colitis, we have equally seen that the longer you wait or the more treatments patients go through, the lower the likelihood they are to respond to some of our therapies. So don't wait. I think in the GI field we as professionals need to embrace these treatments and get our patients on disease modifying therapies earlier.

I also defined what maintenance is supposed to be about— preventing relapse. That means that you have induced remission successfully and then you want to prevent relapse over time so that we can explain this better to our patients and to ourselves.

The fourth point I made in this presentation was about identifying comorbid illnesses or extra intestinal manifestations, thinking holistically about how we manage our patients so that we can understand how to choose therapies based on some of those ideas. In other words, a patient who has an inflammatory skin problem or inflammatory joint problems gives us a clue as to certain treatments that we have available that might effectively treat both problems. But actually, as the emerging data are coming to us, we're learning that when there are 2 organ systems involved or multiple conditions involved, it sometimes provides us a clue to an inflammatory pathway that might even work better.

So if you have a patient with a skin inflammatory condition like psoriasis or atopic dermatitis, we can think about using IL-23 inhibitors, or with atopic dermatitis, even a JAK inhibitor. And knowing about some of the other labels and approved indications, as well as what emerging information we have regarding how to treat these conditions together, can really influence your choice of therapies. I also said that sometimes comorbid illnesses will guide you away from certain therapies. For example, the patient who has concomitant multiple sclerosis is somebody in whom we wouldn't use an anti-TNF therapy. Somebody who has a history of melanoma, we might avoid an anti-TNF. But I went through some of the other safety considerations so that people could understand that sometimes they're relatively contraindicated to use certain treatments, but not absolutely so, and I tried to clarify that for the audience.

My final point, however, was that we should make sure that after we think holistically and we choose our therapies, we actually have a treat-to-target strategy. That means assessing the disease with some benchmarked biomarker. In this individual patient, is calprotectin reliable? Is CRP manufactured in their body and can we use that as a marker, or might we even use an intestinal ultrasound or a flexible sigmoidoscopy to know whether we are achieving the objective control that we need? Treat to target implies working towards improved quality of life by pairing therapies to objective assessments and then reassessing as we make adjustments to our treatments to get our patients where they need to go.

The summary of all this is that we should get people on therapies, any of our therapies that we know are working in advanced conditions, and know that by doing so we're getting them to those goals of remission. So as much as it can be overwhelming to think about all the treatments we now have available in IBD, it's an abundance of options. We should just remember the principles of making sure that whatever you're comfortable using, get your patient on therapy and move through so that you get to that end goal.

I hope you found this summary interesting and informative and I certainly would love to be able to share slides with anyone and you can find this online, and also certainly reach out to me. Thank you very much.