Maia Kayal, MD, on Recycling Biologic Therapy After IPAA

In this podcast, Maia Kayal, MD, discusses her recent research into whether using the same biologic therapy before and after total proctocolectomy with ileal pouch anal anastamosis is associated with treatment failure.

Maia Kayal, MD, is an assistant professor of medicine in gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City.

TRANSCRIPT:

Gastroenterology Learning Network:  Hello, and welcome to another podcast from the Gastroenterology Learning Network. I'm your host, Rebecca Mashaw. Today, we're joined by Dr. Maia Kayal, Assistant Professor of Medicine in the Division of Gastroenterology at the Icahn School of Medicine at Mt. Sinai in New York City.

She's going to discuss a recent study she and colleagues conducted about the effectiveness of using the same biologic therapy for patients who have undergone ileal pouch anal anastomosis for refractory ulcerative colitis, both pre and post-surgery. Thank you for joining us, Dr. Kayal.

Dr. Maia Kayal:  Thank you for having me, Rebecca.

GLN:  In your recent article in Clinical Gastroenterology and Hepatology, you noted that among patients with UC who require total proctocolectomy with ileal pouch anal anastomosis, many develop acute pouchitis, and fewer, but a still sizable number, go onto develop chronic pouch inflammation. How prevalent is this chronic inflammation, and what causes it?

Dr. Kayal:  About 50 to 80% of patients after total proctocolectomy with ileal pouch anal anastomosis will develop acute pouchitis. Of this percentage, about 20% of patients go onto chronic pouch inflammation.

Now, the pathogenesis is still very unclear, but it's theorized to be multifactorial, and really involve a complex interaction between the mucosal immune system in the pouch, the microbiome, and of course, genetics, which is not dissimilar to the etiology of traditional inflammatory bowel disease.

We know from transcriptional studies that the pouch undergoes a proinflammatory shift after the final surgical stage that's consistent with metaplasia in the colon. These changes in the extracellular matrix and the immune system, in combination with the microbiome, all promote a chronic pouch inflammation scenario.

GLN:  You also pointed out that there is no current consensus about the medical management of chronic pouch inflammation. What types of therapy are most commonly used, and how effective are they?

Dr. Kayal:  We have borrowed from traditional inflammatory bowel disease to treat chronic pouch inflammation. Biologics such as anti-tumor necrosis factor agents, anti-integrin agents, and anti-interleukin agents are really what have been used traditionally to treat chronic pouch inflammation.

The data isn't great. The evidence is really based on multiple case reports and retrospective studies, which have demonstrated efficacy of biologics in chronic pouch inflammation. However, truly, there's insufficient evidence to support the use of one biologic over the another.

There was a pretty large meta-analysis of about 311 patients with chronic pouch inflammation who were treated with biologics, and the pooled rate of clinical remission was about 65.7% for infliximab, 31% for adalimumab, and 47% for vedolizumab. These are similar numbers, about 40 to 60%, that we also see in ustekinumab.

GLN:  Your study specifically looked at the utility of recycling prior therapies, of treating patients with the same biologic class, both pre- and post-IPAA. Can you give us a quick overview of your study?

Dr. Kayal:  Certainly. This was a single-center retrospective study of about 83 patients over the age of 18 who had medically refractory ulcerative colitis and required a total proctocolectomy with ileal pouch anal anastomosis.

Their postop course was complicated by chronic pouch inflammation. We focused our study on these patients who were on biologic therapy specifically. We included in our population patients who both had chronic pouchitis and Crohn's disease-like pouch inflammation.

GLN:  What did you find in studying these patients regarding their response to recycled biologic therapies?

Dr. Kayal:  Our results were actually very interesting and shed a lot of light on the topic. On univariable and multivariable analysis, we found that patients who were exposed to anti-tumor necrosis factor agents pre- and post-colectomy were less likely to experience clinical remission compared to those who were anti-TNF-naive presurgery or exposed to a different class of biologic postsurgery.

We also found that age, sex, and pouch duration were not significantly associated with clinical remission. This suggested to us, really, that being on the same biologic pre- and post-surgery was associated with lower rates of clinical remission.

GLN:  Because these patients did not respond or lost response to biologic therapy, does that mean that they had developed antidrug antibodies to these biologics?

Dr. Kayal:  That's a very interesting question. That was actually our initial suspicion, because we know that previous studies have noted higher rates of adverse events related specifically to immunogenicity and antibody development in patients who were exposed to anti-TNF agents presurgery and postsurgery.

In this study, though, we found that the decreased rates of clinical remission and increased rates of pouch failure among patients with chronic pouch inflammation who were exposed to the same biologic class pre and post were more likely related to the mechanistic loss of response, and truly the transformation of the disease target. As now, you're treating a different type of inflammation —chronic pouch inflammation — than you were treating before, which was really more colonic, mucosal inflammation in ulcerative colitis. We don't think in this study that it really had to do with immunogenicity, because most patients were actually on a different anti-TNF pre- and post-surgery.

GLN:  What did you finally conclude from the results of your research?

Dr. Kayal:  The big takeaway point that we concluded was that, when choosing a biologic therapy for chronic pouch inflammation, providers really need to take into consideration the previous biologic that the patient was exposed to and consider initiating a different biologic class such that, if a patient was an anti-tumor necrosis factor presurgery, consider starting an anti-integrin or an anti-interleukin agent postsurgery.

GLN:  What further research do you think needs to be done in this area?

Dr. Kayal:  I think this is a fascinating area that needs a lot more research, truly. I think the first and most important thing for our patients is that it's still not clear which biologic is best for chronic pouch inflammation.

Like I said earlier, we borrow a lot of our treatment therapies—or all of our treatment therapies—from traditional inflammatory bowel disease. We're understanding more that chronic pouch inflammation, while it's on the spectrum of inflammatory bowel disease, it really needs to be studied independently from traditional Crohn's disease and ulcerative colitis.

As a first step, we need to do more comparative effectiveness research to understand which biologic that we have been using is actually most efficacious for chronic pouch inflammation.

Along those lines, and really, to get to that endpoint, we need dedicated prospective randomized control trials that look at biologic use in chronic pouch inflammation, but that incorporate 2 important things that we still don't have in this area: standardized measures of disease activity, and disease targets. In order to develop a great drug for chronic pouch inflammation, we have to understand how we measure disease activity, and then what is our treatment goal? I think there's a lot of studies and ongoing multicenter research groups that are starting to define these outcomes and these disease activity measures.

We're well on our way to getting better randomized control trials and better therapies for our patients.

GNL:  Thanks very much for sharing your insights with us on this subject, and we'll look forward to talking with you again as much research comes along.

Dr. Kayal:  Thank you, Rebecca. It was a great discussion.

GLN:  Thank you.