Dr Rieder discusses available and upcoming therapies and positioning of medications for 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 in Cleveland, Ohio.

TRANSCRIPT: 

My name is Florian Rieder. I'm the Vice Chair and cosection head for inflammatory bowel diseases in the Department of Gastroenterology, Hepatology and Nutrition at the Cleveland Clinic. And I will provide some highlights of this presentation in the AIBD regionals.

The disease burden in patients with Crohn's disease is increasing, and there's an increasing incidence of patients with Crohn's disease. And it's very important to recognize the disease, because treating Crohn's disease early in the disease course, and starting advanced therapy before tissue damage occurs, may be able to prevent future tissue damage. So early therapeutic intervention may result in increased rates of clinical remission and mucosal healing, and reduced rates of complication and disease progression.

We have a large armamentarium of medications to be able to achieve this, which includes the conventional medications, immunomodulators, such as azathioprine or methotrexate, and our biologics, and then, small molecules. But there are a variety of barriers to optimal management of patients with Crohn's disease that need to be overcome, which includes a lack of assessment for objective disease activity and disease risk.

If the disease is treated based on symptoms rather than objective markers of inflammation is a problem, excessive use of corticosteroids is a barrier, or a lack of consideration of patient factors in choosing the right therapy. Comorbid illnesses also have a strong influence on which therapy to choose.

In general, when assessing the treatment selection of patients with Crohn's disease, it is important to separate disease activity, which is the current inflammatory status of the patient— is the disease active or not at this moment? And then the disease risk—how will this patient do in the future?

A variety of risk factors that portend a high risk for patients with Crohn's disease have been described, such as extensive involvement perianal disease, the presence of deep ulcers, need for prior surgical resections, or prior complications.

Once you risk stratified your patients, you need to assess, set the patient goals. For instance, restoring normal bowel function, being able to work, having relationships, and this may vary from patient to patient. And once you've done this, you choose your optimal therapy based on the phase of the disease. Is it induction or remission? What's the need for speed in the patient to achieve remission? To use organ selective therapies before choosing systemic therapies. And then again, comorbid illnesses, such as extraintestinal manifestations, or other immune-mediated diseases need to be considered.

As a first-line, when looking at a network meta-analysis in Crohn's disease in biologic naive patients, anti-TNFs such as infliximab, adalimumab, and then ustekinumab, are the top ranked biologics, in terms of efficacy. Once you've failed an anti-TNF, ustekinumab is the next natural choice, based on the data over vedolizumab.

Most recently, small molecules enter the market in Crohn's disease, which includes tofacitinib in ulcerative colitis. This drug failed in Crohn's disease. There's very strong data from upadacitinib, a JAK1 selective medication. It achieved impressive induction in maintenance data. It also may work in perianal Crohn's disease. So the positioning I just mentioned to you will likely change in the near future.

A brief word on risankizumab because this is a new drug. It recently was approved for Crohn's disease. It is an anti-IL-23 medication, different than ustekinumab, that blocks interleukin-12 and interleukin-23. Risankizumab is selective only for interleukin-23. It worked both in induction of remission and in maintenance of remission, in patients with Crohn's disease, with very solid responses, and is a drug that may be given as a first-line, or after prior biologic use. So after use of anti-TNF or anti-endocrines. And given the clean safety profile of the drug class ustekinumab as well as risankizumab, it may even be used before anti-TNF.

A big debate is, do the selective anti-IL-23s work better than the anti-IL-12/23 medications? And data from other diseases, such as psoriasis, suggests that risankizumab may be superior to ustekinumab, but data in Crohn's disease is awaited, and will likely be read out the end of 2023, or during the first half of 2024.

Ultimately, what we want to achieve in our patient is a treat-to-target strategy, and what does this mean? So no matter what medication you choose, you want to achieve a target in this patient. You want to monitor this target frequently, to make sure you maintain it. Or if the target is not reached anymore, to adjust your therapy. And targets can be short-term targets, such as symptoms, intermediate targets, such as biomarkers, like CRP or fecal calprotectin, and long-term targets, like mucosa healing in our patients. Transmural healing is an aspirational target at the moment. It is not recommended for all our patients but is emerging as a treatment endpoint.

Our closest presentation with safety being very important for therapy choice, and corticosteroids are in the bottom of the safety pyramid. You want to avoid long-term use of corticosteroids. This is followed by thiopurines, JAK inhibitors, TNF inhibitors, with the safest medications we have being vedolizumab and anti-IL-12/23.

The best medication does not work for our patients without shared decision making, and without a successful communication between the patient and the clinician, but also by addressing healthcare disparities, to make sure the patients that want to take the medications are, in fact, able to do so.

So in summary, Crohn's disease increases in prevalence and can take a complicated course. Earlier therapy is better. For all therapies, we want to choose a treat-to-target paradigm, considering patient comorbidities, extraintestinal manifestations, and other conditions. For moderate to severe Crohn's disease, first-line is anti-TNF, or ustekinumab in patients that failed anti-TNF, the likely next choice is either ustekinumab or risankizumab. And shared decision making is critical.

We hope to see you at the AIBD regionals, for a great educational experience. And thank you very much for your attention.