David Schwartz, MD, on the ENTERPRISE Study of Vedolizumab for Perianal Crohn Disease

In this podcast, Dr Schwartz discusses the ENTERPRISE multinational program that examined the efficacy and safety of vedolizumab for perianal Crohn’s disease.

David A. Schwartz, MD, is the director of the Inflammatory Bowel Disease Center and a professor of medicine at Vanderbilt University Health in Nashville, Tennessee.

TRANSCRIPT:

Gastroenterology Learning Network:  Hello, everyone, and welcome to another podcast from the Gastroenterology Learning Network. I'm your moderator, Rebecca Mashaw, and I'm here today with Dr. David Schwartz, who is a professor of medicine and director of the IBD Center at Vanderbilt University.

He's going to be talking to us about a recent study conducted on the efficacy and safety of vedolizumab IV regimens for perianal fistulas in Crohn's disease, also known as the ENTERPRISE study. Thank you for joining us today, Dr. Schwartz.

Dr. David Schwartz:  Thanks, Rebecca. It's good to talk to you again.

GLN:  It's great to have you with us. Let's start out by talking about perianal fistulizing Crohn's disease. How common is this, and what effects does this have on quality of life for patients?

Dr. Schwartz:  Based on a lot of population studies that have been done in the past, it's somewhere probably around a quarter of patients with Crohn's disease will develop perianal fistulas at some point during their lifetime. It's a fairly common complication of Crohn's because of what having perianal fistulas or perianal abscess means, it really does negatively affect a patient's quality of life. Probably it's one of the worst manifestations of Crohn's disease when it comes to impacting a patient's quality of life. We really wanted to do the best we can for these patients because of the negative impact this has.

GLN:  It seems to be an especially challenging condition to treat. Do you know why some patients develop perianal fistulae, and why this is often so refractory to treatment?

Dr. Schwartz:  I don't know if we know 100% why people get perianal fistulas. It just tends to be a phenotype of Crohn's disease because it's probably something, a genetic predisposition that a certain subset of patients have to developing these.

Essentially, what a fistula is a tunnel connecting the rectum in this case to their skin or to another organ. And because stool obviously is going through the rectum where you have this tunnel, stool gets forced into the fistula tract. With that, it drives inflammation, infection, and makes this very difficult to treat, and keeps the fistula active.

Whereas luminal disease, other things, the medicine is a little bit more chance of working because you're not having that constant infection or presence of stool impacting the ability of the body to heal it.

GLN:  In your study, you've mentioned that any TNF combined with antibiotics can provide some clinical benefit, but you also mentioned that current treatments are largely inadequate. Can you explain what you mean by that?

Dr. Schwartz:  Sure. I have been doing this long enough where I actually practiced for a very short period of time during my training before anti-TNFs became available. There is no doubt that anti-TNF antibody really revolutionized how we take care of patients with Crohn's perianal fistulas and are by far in the past the most effective medicine we've had for this.

But you have to understand that prior to anti-TNFs, really only a very small minority of patients would improve. Even our goals of therapy back then were quite a bit different than now. With the anti-TNF agents in the best hands, only about 30 to 40% of patients will achieve fistula healing and maintain that for a year.

That still means that about 60 to 70% of our patients are having persistent perianal disease activity and all that bad connotations that could go along with this as far as quality of life. We really want to do much better for these patients and get these fistulas closed completely and make them completely well.

And so we need other options, and that's where this study was born out of. It was trying to find a novel option, particularly for patients that have been exposed to TNFs, but really had not achieved optimal outcomes.

GLN:  ENTERPRISE was a multinational program that examined the efficacy and safety of vedolizumab for perianal Crohn's. Can you give us an overview of the study's objectives and design?

Dr. Schwartz:  When we first talked about doing this, my goal was to try to get some more data with vedolizumab in perianal Crohn's disease. I figured that the more information we had available, the better it would be as far as guiding clinicians as to whether or not we can use this for perianal Crohn's patients.

When you look at what happened when vedolizumab was approved in Europe, they had a week 10 dose approved, but in the US, they did not. It was reserved for patients that had more refractory disease. It was really, by definition, people with perianal Crohn's disease have more refractory disease.

The purpose was really, one, to get a real handle on how effective vedolizumab is for perianal Crohn's disease, but also to see if giving that extra dose at week 10 would make a difference in outcomes for these patients.

Rebecca:  What about the results? What did you find out about vedo's effectiveness in treating this complication of Crohn's?

Dr. Schwartz:  We were pleasantly surprised that when we look at the entire population of patients treated with vedolizumab at both dose and arms, a large percentage of our patients had both fistula remission and fistula improvements; 54% of patients that received vedolizumab had fistula improvement and 43% of patients had fistula remission or complete closure of 100% of their fistula tracts. That was very encouraging and supports the use of vedolizumab for people that have perianal fistulas.

Interestingly, what we did find though is that the week 10 dosing, the ones that patients that got an extra dose of vedolizumab at week 10, did not do it better than standard dose of vedolizumab. Now, the numbers were quite small, and it wasn't really powered to detect the difference between the 2.

It's hard to know for sure if that's a true finding or if it happened by chance. The takeaway message from this study is that vedolizumab does appear to be a viable option for patients with Crohn's perianal fistulas.

GLN:  This is widely considered a very safe drug in other applications for patients with IBD. Did you see any new safety signals or anything to concern you in terms of its application to perianal Crohn's?

Dr. Schwartz:  It continued to appear to be very safe. There wasn't really any new safety signals that emerged, and it was quite well tolerated.

GLN:  How do you think this might affect clinical practice?

Dr. Schwartz:  I think, hopefully, this will give gastroenterologists a little bit more comfort in using this agent in patients that have started on an anti-TNF and not had adequate outcomes. This would be, in my mind, something to use in patients that had refractory perianal disease who had not responded to an anti-TNF agent, or in patients who, for many different reasons may not be a good candidate for an anti-TNF, but have perianal fistulas.

I do hope that this data will allow clinicians to feel much more comfortable using this in patients with perianal Crohn's disease.

GLN:  Very good. Thanks very much for spending this time to tell us about your study, and we'll look forward to what comes next.

Dr. Schwartz:  Thank you very much. Always a pleasure to speak with you.