Dr Schwartz discusses his presentation on the evaluation and management of perianal fistulizing Crohn's disease from the ACG Scientific Meeting, including review of results from studies of guselkumab, upadacitinib, and vedolizumab as therapies for this often complex and debilitating condition.

David A. Schwartz, MD, is a professor of medicine in the Division of Gastroenterology, Hepatology, and Nutrition and director of the Inflammatory Bowel Disease Center at Vanderbilt University Medical Center.

Perianal Crohn’s Disease: Treatment Options and MRI Monitoring

• Anti-TNF therapy remains the mainstay for perianal Crohn’s disease; earlier advanced therapy may help prevent fistulas, which develop in approximately 25% of patients.
• Guselkumab demonstrated efficacy versus placebo in FUZION. Upadacitinib showed benefit in secondary analyses. STOMP2 reported combined remission in approximately 40% with stem cells embedded in fistula plugs versus 10% with placebo; phase 3 development remains uncertain.
• MRI assessment supports monitoring toward durable fistula remission. Reduced or absent T2 signal is commonly considered a healing feature, although MRI healing remains incompletely defined.

Hello, everyone. My name is Dr. David Schwartz. I'm a professor of medicine and the director of the Inflammatory Biology Center at Vanderbilt University. I spoke recently at the American College of Gastroenterology, which was held here in Nashville, on perianal disease, and I wanted to share some of the key insights I presented at that meeting.

So perianal Crohn's disease is really one of the dreaded complications of Crohn's disease, which can lead to really very awful morbidity with a high rate of incontinence, lower quality of life, and a high rate of comorbid anxiety and depression. And so we really need to know how best to take care of these patients. One of the encouraging things is that even though about a quarter of patients will develop fistulas during the course of their disease, with the earlier use of advanced therapy, we're seeing less and less of patients being diagnosed. with perianal Crohn's disease. And one of the reasons why is that we're using advanced therapy earlier in patients who are at risk of developing perianal disease and hopefully preventing that complication in a significant percentage of patients. One of the hopes in the future is that we'll be able to identify patients with perianal Crohn's disease before they develop clinical symptoms and intervene earlier by starting advanced therapy earlier and preventing that from occurring, maybe even in all patients if we can get to that point.

Some of the other key points I presented in my talk was that we have lots of options now available to treat perianal Crohn's disease. Anti-TNF antibody therapy is still largely the mainstay of therapy. We now know that in order to really optimize outcomes with that agent, we really need to shoot for higher trough levels with troughs above 15, ideally for both infliximab and adalimimab, to really get the best outcomes for these patients.

One of the encouraging things over the last several years is that we have several options now beyond anti-TNFs, which show some promise in treating perianal Crohn's disease, ustekinumab and the IL-23 antibodies being the ones that have been looked at most recently. In particular, the IL-23 antibody guselkumab finished the FUZION study, which was presented earlier this year at a couple of our congresses, and it did show really nice efficacy compared to placebo in patients with fistulized and Crohn's disease. This is now a main option for our patients with fistulas,in particular those that have isolated perianal disease or mild or luminal disease. This is a good first-line option for those patients in that situation.

We also have data with our JAK inhibitors, upadacitinib being the one that's approved in the United States, which in secondary analyses does show some benefit for treating patients with fistulizing Crohn's disease, and I use this largely after anti-TNF failure in patients who have more severe disease.

One of the other points that I talked about in my talk was that we had a lot of promise for the use of stem cells, in particular adipose-derived stem cells, to treat perianal fistulizing disease based on the results of the ADMIRE-1 trial. Unfortunately, the ADMIRE-2 trial was a negative trial and led to the withdrawal of this product from most of the markets in the world and certainly will not be available in the United States to treat fistulizing Crohn's disease. I presented a study earlier this year called STOMP2, which looked at a different approach of using stem cells embedded in a fistula plug to treat fistulizing disease. And that showed really nice efficacy with about 40% of patients in the treatment arm getting combined remission compared to only 10% of placebo. It is still up in the air whether or not a phase 3 trial will occur with this particular agent,however.

The last thing I presented was that really using imaging to improve outcomes is really the key to getting these patients better. I want everyone to consider healing on MRI to be the equivalent of mucosal healing on endoscopy when we treat luminal Crohn's disease. When we can achieve true healing, which is yet to be completely defined, but most investigators consider a reduction or absence of a T2 signal on MRI, one of the features of healing on MRI. When we achieve that, we get true durable fistula remission rates, much like we see when we get to endoscopic healing with luminal Crohn's disease. The outcomes are much better when we can achieve that outcome.

So in closing, I think we have lots of really promising options available for our patients with perianal Crohn's disease. Knowing how to best utilize these agents and using imaging to really leverage the benefits of improved assessment and monitoring can really lead to the best outcomes for patients with fistulized and Crohn's disease. Thank you again for your time and attention. I appreciate it.