Jessica Allegretti, MD, on Recent Advances in Anti-Interleukin Therapies

Dr Allegretti provides key take-home points from her presentation at the AIBD regional meeting on how anti-interleukin therapies work to treat both Crohn's disease and ulcerative colitis,

Jessica Allegretti, MD, MPH, is medical director of the Crohn's and Colitis Center at Brigham and Women's Hospital in Boston.

Hello everyone, my name is Jessica Allegretti and I'm the medical director of the Crohn’s and Colitis Center at the Brigham and Women's Hospital in Boston. And today I had the pleasure of presenting at the regional AIBD conference and the title of my talk was "Improving Quality of Care," really examining the new novel IL -23 mechanism and its role in the management of patients with inflammatory bowel disease.

Now we began by discussing the challenges that we face with managing patients with IBD currently. There are many therapeutic decisions that we have to think through. One patient factor is how does the patient want to receive drug? How fast do they need to feel well? What's the speed of onset? Safety considerations? Do they have other comorbidities that we need to be mindful of? And do they have any other safety considerations like malignancy or other factors that may differentiate what agent we might ultimately choose?

Now we still recommend treat -to -target metrics using the STRIDE 2 guidance and really having a shared decision -making process with your patient. But luckily in 2024 we have really an expanding armamentarium of therapies to use in our patients. And so I'm here to discuss this really evolving class of therapies, the anti -IL-23s. Now we have a lot of experience with an anti -IL12/23, which is ustekinimab, and that drug specifically binds the P40 subunit, which is present on both IL12 and 23.

The difference between this new class of drugs is they specifically bind P19, which is only present on IL-23. Now you might be asking, well, what is the benefit to only blocking IL -23 compared to IL-12? And we know that by doing that, we keep intact the IL -17 pathway, which is shown to be protective. So there may be a safety and even potentially efficacy benefit to only blocking IL -23 and leaving IL-12 intact.

There are currently three agents within this space. The first that was approved for Crohn's disease is risankizumab. Mirikizumab was the first approved for ulcerative colitis and we also have guselkumab, which is currently under investigation for both.

And so this is a really expanding class of drugs and we've got a lot of really good options. Now the next question is how are we going to possibly differentiate among these three? We know from all of the phase 2 and phase 3 clinical trial data from these programs they all work very well in bio -naive patients, but what's notable about this class is that it performs very well in patients who are bio -experienced as well, especially those who have been previously exposed to an anti -TNF, and so that's certainly a benefit. Also, these drugs are convenient and we've got tremendous amount of safety data showing that this class is a safe class of drugs.

How are we going to actually differentiate among them though is a bit more complicated and we do have some signals right now even on the molecular level that may help us. And so we know specifically when we look at risankizumab and guselkumab they have similar binding affinity when we look in the serum for IL -23 so they perform very similarly. However, at the molecular level, when we look at IL -23 in the mucosa, we know that a lot of that IL -23 comes from CD64 positive cells. Now CD64 is a receptor present on certain types of cells, specifically myeloid cells, which are very prevalent in patients with inflammatory bowel disease. And so what we know about these drugs is that guselkumab, because of how it’s engineered, binds very effectively to CD64. and therefore it can bind up all the IL -23 from the site of origin before it gets released out. And so really at the deep molecular level, you may be able to see more targeted affinity from this agent compared to some of the others in the class.

And so I don't think this is the whole story. I think this is an evolving story about how we might be able to differentiate among these 3 and potentially more agents coming.

And so in summary, this is a very safe, very patient -friendly class of drugs that we now have options in both Crohn’s and ulcerative colitis, again, with more coming. And I think an evolving story on how we might ultimately differentiate among them. But overall, I think this is great for patient care and great for providers to have more choice. So thank you so much for your attention.