Edward Barnes, MD, on Emerging Management of Disorders of the Pouch

In this video, Dr Barnes discusses the highlights from his presentation on Emerging Management of Disorders of the Pouch from the Advances in Inflammatory Bowel Disease regional meeting on September 25.

Edward Barnes, MD, is an assistant professor of medicine and gastroenterologist at the University of North Carolina at Chapel Hill.

TRANSCRIPT

Hi, I'm Ed Barnes from the University of North Carolina. I had the pleasure of talking about the management of pouch-related conditions here at AIBD Regionals.

What we tried to do today in this particular discussion of pouch-related disorders is not just think about the most common pouch-related disorders and how we manage those—those being acute pouchitis or even chronic antibody-dependant pouchitis—but what do we do when we have a pouch-related disorder that's complex and we have to think outside the box?

We talked a lot about, what are some emerging ways to think about treating pouch-related disorders, and how do we think beyond our standard of pouch-related algorithms?

This is an exciting time to think about treating patients with inflammatory conditions of the pouch, because these can be some of the most complex patients that we treat.

If we do think outside of the box, we have an opportunity to improve outcomes among some, again, as I said before, some of the most complex patients that we treat.

Just to remind you, these inflammatory conditions of the pouch are very common. About 40% of patients will develop acute pouchitis in the first year after they have surgery, after they have an ileal pouch-anal anastomosis.

What we focused on are the people that have chronic pouchitis. The 20% of patients that develop chronic pouchitis, and in particular, that minority of patients that have chronic antibiotic-refractory pouchitis, or the 10% of patients that go on to develop Crohn's-like disease of the pouch.

Thinking about the chronic pouchitis patients first, and we take a step back and we think about that chronic antibiotic-dependent pouchitis population, we know that the microbiome is heavily involved in the development of pouchitis.

We see that because patients, as I mentioned before, will respond to antibiotics, and the patients that are chronically on antibiotics seem to respond if they have antibiotic-dependent pouchitis.

This has led many researchers to think, "Can we restore the microbiome, or can we change the microbiome, to manipulate the microbiome to make those patients less dependent on antibiotics?"

This naturally has led to an interest in the use of fecal microbiota transplant as a potential therapy for the treatment of chronic antibiotic-dependent pouchitis. To this point, the evidence is out there that this hasn't been proven to be effective as an approach, I should say.

There's been a couple of trials that have looked at this in detail, one from Helsinki and one that we did here at UNC led by Hans Herfarth. This has not led to great results thus far. There have been other groups that have looked at this as well, but I highlighted these two in my talk today.

One of the reasons that this may not be an overwhelmingly effective approach thus far is that we may not be able to rely just on a single-donor stool approach. You may need a more heterogeneous approach, because you may need a different type of engraftment that you need for other studies of fecal microbiota transplant.

We probably have more to learn in the use of fecal microbiota transplant, FMT, in patients that have chronic antibiotic-dependent pouchitis. I've mentioned already before, but a lot of the talk that I did focus on those patients that have more of the refractory pouchitis conditions, those patients that don't respond to antibiotics.

One of the questions then becomes, if we're going to use a biologic or we're going to use a small molecule, how do we think about those patients if they've already been exposed to a biologic or a small molecule before they had their colectomy, before they got their pouch, when they were being treated for ulcerative colitis?

There's a very interesting study that's just been recently published from Maia Kayal and colleagues at Mount Sinai that said that if you use the same biologic or the same class of biologics that the patient was on pre-colectomy, if you recycle those biologics, potentially, that's a less effective approach than using new biologics or new classes of biologics.

This is something that we've been interested in looking at, in terms of, what is the efficacy of what I would consider a novel biologic, not the non-anti-TNF biologics, ustekinumab or vedolizumab, or small molecules like tofacitinib?

We reviewed some of that data, both from retrospective cohorts and multicenter studies, some case reports of the use of tofacitinib where there seems to be efficacy in the treatment of Crohn's-like disease of the pouch.

Also, some prospective study that we've been collecting from a multicenter registry through the Crohn's & Colitis Foundation's clinical research alliance known as PROP-RD, where there seems to be good durability for these novel biologics, and that about 50% of patients seem to be in remission about six months after they enroll into the prospective registry.

If these therapies are not effective, then we do have to start to think outside the box. One of the really outside-the-box and novel ways to think about treating patients with inflammatory conditions of the pouch, and one that I think is exciting and cutting-edge, is the use of hyperbaric oxygen therapy in the treatment of inflammatory conditions of the pouch.

These studies are relatively small, but they are exciting to think about how effective they seem to be. In a retrospective study of 21 patients with mixed inflammatory conditions of the pouch, there was overwhelming efficacy for the treatment of both the inflammation of the pouch, but in particular, patients that had a fistula related to an inflammatory condition of the pouch.

In seven of the nine patients that had a fistula, they had complete closure, complete healing of the fistula, documented by both the cross-sectional imaging and endoscopic evaluation. This is an exciting way to think about treating patients that are probably the most refractory. They're refractory to our common medicines, they're refractory to our biologics.

Hyperbaric oxygen therapy may fill an important hole that would potentially save their pouch and prevent pouch failure. There are important questions to answer about hyperbaric oxygen, such as access to the therapy, and how effective can the therapy be, and what are the costs of the therapy in larger studies?

This is an exciting way to think, again, outside the box as we think about treating these patients with the most refractory conditions of the pouch. These are just a few of the exciting things that I touched on as we think about the most emerging ways to treat these patients.

I hope that this conversation was helpful, and I hope this prompts us to think about how we can improve the care of our patients with all inflammatory conditions of the pouch. I thank you very much for your interest.