Florian Rieder, MD, on Positioning Drugs in Crohn's Disease

Dr Florian Rieder from Cleveland Clinic spoke at the AIBD Regional Meeting on how he approaches positioning different therapies among patients with 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.

My name is Florian Rieder, I'm the vice chair for the Department of Gastroenterology and Pathology and Nutrition, cosection head of inflammatory bowel diseases and the director for the Global Translational Program for Inflammatory Bowel Diseases at the Cleveland Clinic. I'm talking to you in the AIBD Regionals and I'm happy to give you a recap on my presentation on positioning in Crohn's disease.

Positioning is getting increasingly important because we need to understand how to get the right drug to the right patient. We made great progress because beyond the classical immunomodulators and the early biologics, in particular in anti-TNFs, we now have anti-interleukin molecules, anti-IL-12/23 and anti-IL-23, but also small molecules such as JAK inhibitors or S1P modulators.

So how do we determine what is the best position for which drug in our patients? And to do that, we need comparative effectiveness studies. They compare efficacy, effectiveness, and safety based on several data sources, such as randomized controlled trials against placebo, head-to-head trials of 2 different biologics, observational data, as well as safety information from clinical trials and registries.

So I'm going to give you a brief summary recommendation on how I personally position drugs in moderate to severe luminal Crohn's disease in 2024.

Separation is biologic-naive versus a biologic-experience patients, and I focus on luminal Crohn's disease without perianal disease. In biologic naïve patients, I still feel that anti-TNF in combination therapy or an anti-IL23 are the best choices for our patients—anti-TNF in combination therapy because it's shown to work better compared to anti-TNF alone and the anti-IL-23 and anti-IL-12/23 and anti-TNF adalimumab had comparative effectiveness in moderate to severe Crohn’s disease. And most recently a landmark trial compared an anti-IL-23, risankizumab, with anti-12/23, ustekinumab, in moderate to severe patients and showed better endoscopic healing in patients with risankizumab compared to ustekinumab, so it seems to be the better choice for our patients.

Hence, anti-TNF in combination therapy and anti-IL-23 is first choice for anti-TNF naive patients. Vedolizumab should not be discounted in anti-TNF naive patients, particularly in the ones on the moderate side of the spectrum, at a milder end of the moderate side of the spectrum. I do not use it unless I have to with patients that failed an anti-TNF therapy.

So how do you treat patients that have previously been exposed to an anti-TNF? Here we recommend an anti-IL-23 over an anti-IL12/23. again because of the head-to-head trial comparing the two, or a JAK inhibitor; in this case, upadacitinib seems to have the strongest effect. Tofacitinib showed negative phase 2 trial data in patients with moderate to severe Crohn’s. The JAK 1 inhibitor upadacitinib had a robust effect even in patients that have been exposed to anti-TNF prior.

We recommend biologics over thiopurines for induction of remission, but ideally in combination therapy— infliximab and thiopurine, or infliximab and methotrexate, or adalimumab and thiopurine and adalimumab and methotrexate over infliximab alone. It's important to understand therapy -specific safety concerns, and here the safest drugs we have are anti-IL-23, anti-IL-12/23, vedolizumab, and the S1P modulators, but I have to mention that the safety is not only determined by the inherent safety of the drug itself, but also by its anti-inflammatory effect. So if the drug has a very strong anti-inflammatory effect, the safety is going to be better than in a safe drug that has a weak anti-inflammatory effect, because active disease itself is an adverse effect.

With this, I would like to close and I hope to see you again at the AIBD Regionals in the near future. Thank you for listening.