Florian Rieder, MD, on Endoscopy and Beyond in Crohn's Stenosis

Dr Rieder reviews his keynote address on diagnosing and treating stricturing Crohn's disease, including the use of medical, dilation, and surgical options.

Florian Rieder, MD, is vice chair and cosection director for inflammatory bowel diseases in the Division of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic.

TRANSCRIPT:

My name is Florian Rieder. I'm the vice chair and cosection director for IBD at the Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic in Cleveland, Ohio. And I will talk to you about my keynote, endoscopy and beyond in Crohn's stenosis.

Crohn's stenosis is a significant clinical problem, with more than half of patients developing clinically apparent stricturing disease, in patients with small bowel Crohn's disease. And this can be diagnosed with endoscopy and the impossibility to pass, or difficulty to pass, an adult endoscope, which is part of the endoscopic scoring systems, SES-CD and CDIS. But the main modality really is cross-section imaging, where you look at features such as wall thickness, luminal narrowing in prestenotic dilatation. Using those, the accuracy is very high, in the ‘90s for CT and MR. Sensitivity is a bit lower for ultrasound, and that's because the entire small bowel is harder to assess; but if it's in the terminal ileum, also for ultrasound sensitivity, detection of stenosis is high.

We are not able with routine techniques such as MRI to distinguish the amount of fibrosis and inflammation in the stricture. And both of them robustly overlap, come together and correlate with each other, which makes a complete separation difficult. And there are a lot of experimental techniques being evaluated to accomplish this to help us in the future in clinical practice.

So when we have diagnosed stenosis, how do we treat it? And we arrive in the era of biologics, and we now have randomized controlled data with anti-TNF in stricturing disease as showing, in fact, robust efficacy that in symptom reduction after 1 year, wherein the probability to stay intervention-free during follow-up and intervention-free for stricturing disease would be free of surgery or free of endoscopic balloon dilation.

We now have emerging data with novel molecules such as risankizumab, an anti-IL 23 antibody, and upadacitinib, a JAK inhibitor, that indicates in post-hoc analysis from the registration trials that patients on these drugs have a reduction in the stenosis component of the endoscopic score SES-CD. So while this doesn't show antifibrotic effect, it shows that they may work in patients that already have pre-existing stenosis on endoscopy.

We do have the option to balloon dilate our patients, and observational data suggests that this is highly, and about 80% of the patients feel better almost immediately. And within 1 year, half of them need redilation; only 30% need surgery. And as you can dilate multiple times in a patient sequentially with about the same efficacy, this is an option for patients with short strictures, less than 5 centimeters, that are in reach of endoscopy, but don't have any associated abscess or internal penetrating disease.

And when do you do surgery or what favors surgery? Surgery is favored if patient doesn't respond to medical therapy; if dilation is technically difficult, long, or multiple strictures; and early recurrence of symptoms after dilation and then concomitant symptoms such as abscess, fistula, phlegmon, dysplasia, and/or malignancy.  Colonic strictures are a different beast because you have a higher risk for dysplasia or malignancy, which across the board if you have colonic Crohn's disease in more than one-third of the colon, or if you have ulcerative colitis, the risk for dysplasia or cancer after excluding it with endoscopy, is still about 3.5%. Meaning even if we do the best we can in excluding dysplasia or cancer by endoscopic biopsies, imaging, and so on, there is still a residual risk for colonic dysplasia or malignancy.

And I'll close with an outlook into the future because it's a large gap between this unmet need of stricturing disease and then therapeutic strategies for antifibrotics in other organs.  And there is a global group called the STAR Consortium that is developing the clinical trial endpoints for a stricturing disease that includes MRI, CT…

So there is a patient-reported outcome tool, and this led to the first clinical trial where a patient got dosed with an selective antifibrotic therapy, in this case, a gut restricted so-called L5 inhibitor. It blocks signaling of profibrotic cytokine called transforming growth vector beta 1. So this L-5 inhibitor is now tested in a phase 2 program in patients with strict gene Crohn's disease.

So in summary, you want to control inflammation as a first step in therapy of stricturing gene disease. You can dilate short strictures in reach of endoscopy. You want to resect in case of concomitant features such as fistula, abscess, phelgmon, or malignancy. Colonic strictures will be carefully surveyed because there remains to be a risk of malignancy, and novel clinical trial endpoints will enable or, or already enable, testing of antistricture therapies in Crohn's disease. Thank you very much for your attention, and I hope to see you at the AIBD regionals in the coming year.