Dr Rieder reviews the options for treatment of Crohn's disease in terms of  safety, treatment of comorbidities, and efficacy for moderate to severe 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

Hello, my name is Florian Rieder and I'm the vice department chair for gastroenterology, hepatology, and nutrition and the cosection director of inflammatory bowel diseases at the Cleveland Clinic. I'm talking to you today at the AIBD Regionals, where I just completed a presentation on optimizing therapies in Crohn's disease. I'd like to give you a brief recap of.top points of this presentation. And I think there are several key take-home messages.

One is that earlier is better for all therapies. So the earlier a Crohn's disease patient receives effective anti-inflammatory therapy, the better this patient is going to do in the future. We are using treat to target, in fact treat the patients not only based on symptoms, we also consider other targets, objective markers of inflammation, such as endoscopy, biomarkers like C-reactive protein and fecal calprotectin, but also the quality of life of the patient.

We develop the target together with our patients because they may have a different goal than us as physicians. There are in fact studies showing the patients may have a different outlook on disease and put different emphasis on certain symptoms and phenotypes compared to physicians.

So how do we position therapies to optimize outcome in patients with Crohn's disease? The two big factors we consider when choosing the right therapy is the disease activity—so what is the state of inflammation at that moment?—and then the disease severity, which is the future risk for past presence of certain complications, such as extensive disease, stricturing disease, internal penetrating disease, perianal disease, and so on.

So I would eye position in totality of the data the drugs from moderate to severe Crohn's disease. So in first line, meaning biologic naive patients without perianal disease, I still think that anti-TNF as a combo therapy or an IL-12/23 or 23 are the best choices.

There's recent data comparing directly the anti-IL-12/23 ustekinumab with the anti-IL-23 risankizumab, with risankizumab having in fact superior effect on endoscopic outcomes in moderate to severe Crohn's disease when compared to head-to head. So as a first line, I think risankizumab or anti-TNF combination therapy are the most reasonable choices at the moment.

If a patient has perianal disease, I still use anti-TNF combination therapy predominantly because we have the most solid evidence that this is the strongest drug. We can titrate the drugs because these patients do better, we believe, based on the data with higher drug levels compared to luminal disease.

What if the patient was under anti-TNF or anti-TNF combination therapy and failed anti-TNF? And here we have two major choices. One of them being an anti-IL- 23, and again, likely better than an anti-IL-12/23 is the anti-IL-23 alone, in this case, risankizumab, which is approved for Crohn's disease. And the other alternatives are JAK inhibitors, small molecules, which have very strong efficacy in patients, biologic-naive or post-anti-TNF failure only in the United States, you can at the moment only give this drug after an anti-TNF failure.

Vedolizumab is approved for Crohn's disease. I do not use it unless I have no other choice in anti-TNF failures, but in moderate or the milder side of moderate Crohn's disease patients that are biologic naive, I think vedolizumab is a very solid choice. One additional consideration for choosing the right therapy are other comorbidities and if you have skin diseases such as eczema or psoriasis, an anti-IL-23 is a good choice. If you have atopic dermatitis or joint involvement, JAK inhibitors work very well. If you have diabetes, you obviously want to avoid any corticosteroids. And in general, we would like to spare the patient of long courses of corticosteroids.

The final word on safety, then, on top of the safety pyramid are anti-IL-23, anti-IL-12/23, S1P inhibitors, or S1P modulators, and vedolizumab, in my opinion. But one can say that the stronger the drug works, the better is the safety. So one could argue with all the drugs that are approved, the safest drug is the one that controls the disease best.

And the second point is that involving the colorectal surgeon early is also part of the therapeutic armamentarium and, for instance, if you resect limited disease without any complications early on before the patient is even seen a biologic that has a dramatic impact on long-term outcome of these patients in a positive way.