Edward Barnes, MD, on Positioning Anticytokines and Anti-Integrins in IBD

Edward Barnes, MD, from the University of North Carolina-Chapel Hill, reviews his talk on positioning therapeutics in IBD treatment from the September 12 virtual Advances In Inflammatory Bowel Disease regional meeting.

Edward Barnes, MD, is an assistant professor in gastroenterology and hepatology at the University of North Carolina Medical School at Chapel Hill.

 

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TRANSCRIPT:

I'm Edward Barnes, and I'm an assistant professor at the University of North Carolina at Chapel Hill. I've had the pleasure to present on the management of pouch complications.

I'd like to just take a few minutes and talk about what we've just discussed in our Advances in IBD regional presentation. The most common surgical management procedures for ulcerative colitis ‑‑ when surgery is indicated ‑‑ is to perform a colectomy with an ileal pouch‑anal anastomosis.

Now, this is often really billed as a curative surgery for patients with UC. This can be associated with many different complications.

The most common complication for a patient that has an ileal pouch‑anal anastomosis that's performed for UC is acute pouchitis, with approximately 40% of patients developing acute pouchitis within the first year, and up to 80% of patients developing pouchitis symptoms at some point over the disease course after they have an IPAA.

In addition to having acute pouchitis, 17% to 19% of patients will go on to develop chronic pouchitis. That can really be problematic because patients can either have chronic antibiotic-dependent pouchitis, where they're really requiring antibiotics to keep their symptoms at bay. Or they can have a chronic antibiotic refractory pouchitis, where the most common antibiotics that we use to treat pouchitis don't respond anymore.

Because they don't respond to antibiotics, they're really having to ratchet up their therapies. They're requiring things like biologics or other immunosuppressive therapies.

We also talked a lot about other inflammatory conditions of the pouch that would include things like Crohn's‑like disease of the pouch. This is a really problematic diagnosis for patients because in spite of preoperative diagnosis of ulcerative colotis, we know that about 10% of patients will go on to develop this Crohn's‑like disease of the pouch.

This is problematic for a variety of different reasons, not the least of which is heterogeneity and the literature that describes the condition.

Crohn's‑like disease of the pouch has been described by several different terms. There are several different diagnostic criteria that have been used to identify a patient with Crohn's‑like disease of the pouch, the most common being either inflammation of the pouch above the level of the pouch, the prepouch ileal, or development of strictures in the pouch body or the prepouch ileum, or the development of fistulae.

The other complications that we think about don't have to do with just inflammation. We talked a little bit about complications like pouch failure. Luckily this is uncommon, but it does occur in about 4% to 10% of patients at some point after a surgery to formulate a pouch‑anal anastomosis. We also talked about the potential to develop dysplasia of the pouch. Again, this is uncommon.

Less than 1% of patients will develop dysplasia or cancer after an ileal pouch‑anal anastomosis for ulcerative colitis. But there are risk factors for identifying these patients that may develop dysplasia or may develop cancer of the pouch. If you have a patient that has a risk factor, then that may change your surveillance strategy.

Those risk factors we would look out for would be things like a prior diagnosis of colorectal cancer as an indication for a colectomy, a prior diagnosis of colorectal dysplasia as an indication for a colectomy, or a concomitant diagnosis of primary sclerosing cholangitis. If you have one of those high‑risk factors, that would be a patient that you would think about doing a yearly surveillance with a pouchoscopy.

If you don't have a high‑risk factor, then you might not need a yearly pouchoscopy, and we might could do a less frequent pouchoscopy strategy. In some cases, some society guidelines have recommended doing pouchoscopy about every 5 years in those patients.

We've talked about a bunch of different complications and what those might consist of. We've talked a little bit also about the management of those inflammatory conditions of the pouches.

I think one of the most exciting ways to think about managing patients that have particularly the chronic inflammatory conditions such as chronic antibiotic refractory pouchitis and Crohn's‑like disease of the pouch is really the use of biologics and other more immunosuppressive regiments that we use in other forms of inflammatory bowel disease like Crohn's disease, de novo Crohn's disease, and ulcerative colitis.

We've seen some really, I would say, exciting literature that's emerged in the last several years regarding the treatment of these chronic inflammatory conditions of the pouch.

Those would include the use of novel biologic agents like ustekinumab and vedolizumab, as well as more standard agents like anti‑TNF therapies. We've even seen case reports of the use of tofacitinib in the treatment of these patients.

I think when we think about treating these conditions, we really want to limit the burden of disease, and so it's exciting to know that these agents may work in these conditions, but we also want to know about the durability and relative comparative effectiveness of these agents. I think we've got some work to do to think about how we would position these agents as well.

I hope that this was a really informative discussion for the participants in the AIBD regional conversation today. I hope that it will prompt us to really start to fill in some of these gaps when we think about treating complications of the pouch and really improving the care of patients with ileal pouch‑anal anastomosis after a colectomy for ulcerative colitis.

Thank you very much for your attention, and I hope that this was an informative discussion for you.

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