Florian Rieder, MD, on Optimizing Treatment for Luminal Crohn's Disease

Dr Rieder reviews his presentation from the Advances in Inflammatory Bowel Disease regional meeting on removing barriers to optimizing treatment for luminal Crohn's disease.

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

Florian Rieder:

Welcome. My name is Florian Rieder, I'm the Vice Department Chair for Gastroenterology, Hepatology, and Nutrition, and the cosection head for inflammatory bowel diseases at the Cleveland Clinic. I'm excited to talk to you about the topic of luminal Crohn's disease because it is is still a significant unmet need but we have hope because, just in the recent year, we have a lot more therapy options to treat our patients, particularly with moderate to severe Crohn's disease. In addition to anti-TNF and vedolizumab as well as anti-IL-12/23, we have recently approved anti-IL-23 risankizumab and also a JAK-1 selective medication, upadacitinib.

Positioning of the drug can depend on a variety of factors, which is efficacy, safety, comorbid conditions, patient age or, particularly, features in an often individual patient before you start therapy. In terms of pure efficacy, all these drugs have been shown to be efficacious but, as a first line therapy, infliximab and network meta-analysis has shown the strongest effect, followed by adalimumab and ustekinumab. A direct head-to-head trial comparing adalimumab and ustekinumab showed the equivalence of both drugs for induction maintenance of moderate to severe Crohn's disease.

Vedolizumab, which is a gut selective trafficking agent, inhibits trafficking of alpha 4 beta 7 positive lymphocytes into the gut mucosa, works particularly well in patients with a moderate spectrum of Crohn's disease that have a low CRP and normal albumin so patients that have moderate disease activity and even in small bowel disease appears to work quite well. The new kids on the block are risankizumab, which is other than ustekinumab, which is an anti-IL-12/23 molecule. It's an anti-IL-23 molecule with positive data. And then, the JAK inhibitor, upadacitinib, which is the first oral JAK inhibitor available for Crohn's disease, with very strong data for induction and maintenance of remission.

Special situations in Crohn's disease are perianal disease, and here the randomized control data is available for infliximab and we have post-hoc data available for vedolizumab, ustekinumab, and upadacitinib that all appear to work for perianal disease, and so do the other anti-TNF, adalimumab and certolizumab. Most recently, a randomized controlled trial for vedolizumab for perianal disease was completed, the so-called enterprise study, with a head-to-head high dose versus regular dose vedolizumab comparison, which also helped our patients with perianal disease. One other big consideration is safety. From a safety perspective, the least safe drugs is corticosteroids and then likely combination therapy of anti-TNF and thiopurine, followed by JAKs and anti-TNF.

The safest drugs in the armamentarium are the anti-IL-12/23, anti-IL-23, vedolizumab, and then S1P receptor modulators that are not yet approved for Crohn's disease but is in ulcerative colitis and likely will come for Crohn's disease in the future. One important closing statement is that we recommend to use treat to target therapies, so you try to achieve a target with your patient together that can be a short-term target, like symptoms, an intermediate target, like biomarkers, or a long-term target, like endoscopic healing. Once you settle to a target with your patient, you want to monitor the target frequently, if you don't achieve it, adjust your therapy. If you achieve this target, you want to maintain the target.

At the end of all of it, shared decision making is critical, which also helps addressing healthcare disparities in our patients because without the patient's ability to believe in the drug and to actually take the drug and have the infrastructure to do so, we can recommend whatever we want, it will not have an effect. Thank you for listening and we hope to see you soon at any of our AIBD regional events. Have a good day.