Expert Perspectives on the Optimal Management of Inflammatory Bowel Disease - Episode 14
Current treatment limitations in inflammatory bowel disease and the rationale for earlier initiation and use of newer therapies to manage pediatric and adult patients.
Stephen Hanauer, MD: One of the issues has been that there does appear to be a therapeutic ceiling with all our agents. We’re seeing about 40% to 60% clinical remissions along those lines, depending on where these drugs are positioned. Both of us have been very aggressive about trying to get these drugs earlier in the course to prevent complications. If you look in the clinical trials with ustekinumab or vedolizumab, the average duration of Crohn disease is 10 years. Patients with 10 years of disease are already developing the problems that we’re trying to prevent. One of the things that I would like to focus on in the future is earlier intervention with these highly effective therapies that we’ve been discussing. What other unmet needs do you see in the pediatric and adult populations for IBD [inflammatory bowel disease]?
Marla Dubinsky, MD: I also have a very keen interest in preconception and fertility in the management of women’s reproductive health, which does tie in to everything we’re talking about. The message to all our female patients is that it’s all about safety and being able to have your disease under control. It is paramount that having anti-inflammatories onboard is what is most important. We know the risk benefit profiles associated with therapies and how to use these therapies in pregnancy, particularly the biologics. We need to be focused on teaching the right thing to our physician partners and patients, that it’s all about controlled inflammation.
Chronic pelvic inflammation can never end well. That is something I’m vocal about within my preconception clinic, and I counsel women appropriately. But it does have to do with some of these small molecules. We’ll add a layer of complexity when we are looking at bringing these therapies to the clinic. With some therapies, such as the small molecules, we don’t have a lot of real-world experience on the impact in the first trimester because they cross the placenta. That is the question that we need to get more data on. For example, with ozanimod, it will be in the label to stop 3 months before conception. With JAKs you need to stop it. It does add a layer of complexity—we’ve become ob-gyns in terms of figuring out how to use these therapies. An unmet need is also understanding the safety of these therapies in women of reproductive age.
Stephen Hanauer, MD: Did that also apply to pediatric patients? Are there other unmet needs besides improving the efficacy and maintaining a good safety profile in kids?
Marla Dubinsky, MD: It’s a similar concept once you get beyond the VEO [very early onset] IBD. We have the same principles. Similar to what you talked about, whether those extraintestinal manifestations were activity linked or not, the same applies to growth. For all our therapies, just because you heal the intestine, does not equate to growth improvement. We don’t know. We need more data. Does gut-specific therapy have the same impact as systemic therapies? These are things that we need to see from our clinical trials.
There are a couple of unmet needs that you made me think about. I do believe, as I noted before, the future is combination therapy. It could be diet plus biologic. It could be small molecule plus biologic. It could be fecal restorative therapy. It doesn’t matter. The concept of combination means that 1 therapy alone is not going to be the answer. I was addressing your plateau. This is the way I’m thinking about it. Also, sequence will be a hugely important topic to address, meaning understanding the sequence over the long lifetime of a patient who has an evolving immune system based on the therapies we’re using.
I have to plug something that both you and I believe strongly. The plateau may also be the fact that we are not addressing the emotional or behavioral well-being of our patients in clinical trials or the real world, so we can understand how social determinants of behavior, mental health, and comorbidities impact outcomes. We may see a different percentage of remission at week 52. That is an important unmet need that we need to focus on.
Stephen Hanauer, MD: I want to amplify your recognition of the social determinants. Certainly in 2021, we’ve seen social determinants of COVID-19 infections and increasingly recognize the disparities of health care in treating chronic illnesses such as ulcerative colitis, Crohn disease, inflammatory bowel disease. We really need to address these disparities and try to improve, whether it’s with psychology, social workers, diet, and education. All these combinations—as your group and our group have shown—really impact patients. They keep them out of the emergency department. Keep them out of the hospital. We need our systems to help us address these disparities. As practitioners, it’s challenging for us and our staff to address this full spectrum of the patients’ needs, from diet to psychological or behavioral support. Economically, 1 of the biggest issues we all have is access to these highly effective therapies. We’re dealing with different insurance programs that may not allow us to use these drugs in the most effective manner that we think we could.
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Transcript Edited for Clarity