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Optimizing outcomes in IBD care
Are You Starting From the Top in IBD? New Guideline Recommendations in IBD Treatment Selection

Released: April 21, 2026

Jessica Allegretti
Jessica Allegretti, MD, MPH, FACG, AGAF
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Key Takeaways
  • HCPs must accurately risk stratify patients with IBD, requiring particular attention and clinical know how, as this will ultimately inform the appropriate treatment approach to take.
  • The updated guidelines for UC now condense the list of efficacious options for patients without prior advanced therapy, streamlining the treatment selection process for HCPs.
  • Developing a strong monitoring strategy and adapting treatment based on real-time outcomes are essential to employing treat to target in patients with CD.

Both the American Gastroenterological Association (AGA) and American College of Gastroenterology guideline updates acknowledge heterogeneity in the course of inflammatory bowel disease (IBD). And when healthcare professionals (HCPs) think about high-risk vs low-risk patients with IBD, often this is something that we must consider when we are deciding with patients if it is appropriate to start an advanced therapy upfront.

There are several risk factors that identify those at high risk of developing complications, and approximately 80% of patients have at least 1 of these risk factors. In determining risk, HCPs should look at patients’ disease extent and duration as well as the severity of present ulceration. Those with deep punched-out ulcers in Crohn’s disease (CD) and a Mayo Endoscopic Score of 3 in ulcerative colitis (UC) are at high risk. Other risk factors include the severity of inflammation, history of Clostridioides difficile infection, prior use of corticosteroids or surgical resection, and prior hospitalization. Finally, patients younger than 30 years of age at diagnosis are at high risk for disease progression. Therefore, HCPs should start these patients on appropriate therapy as early as possible because we actually can alter the natural history of their disease.

Now, there are patients at low risk for disease progression, but I think we need to get better at recognizing those who fall into the moderate-risk and high-risk categories. It is likely that many patients with IBD are inappropriately assigned low-risk disease. Certainly, if patients have minimal disease and are borderline asymptomatic, they can be at low risk. In these patients, especially those with UC, HCPs may start them on conventional therapy and observe them for response. All of which is in effort to address a persistent issue: We are likely underusing advanced therapies in perceived low-risk patients who actually are at moderate to high risk.

UC Management in Patients Without Prior Advanced Therapy
The updated AGA guidelines offer help to HCPs to think about the positioning of therapies for first-line treatment for patients with UC without prior advanced therapy, that is, previous versions of the guidelines used to simply list all efficacious therapies that were better than placebo. Now we have this tiering of choices—from agents with higher efficacy to those with intermediate and lower efficacy. 

For patients with newly diagnosed UC in whom HCPs are unsure which treatment to choose, the guidelines will not say to absolutely use agent A vs agent B. Instead, the guidelines provide a condensed list of all the high-efficacy therapies that might be appropriate. HCPs then should spend time with patients to determine which therapy from that condensed list is most appropriate for them. 

In addition, there are several factors to consider that will ultimately inform the treatment decision HCPs and patients make. These include speed of onset needed, comorbidities present, extraintestinal manifestations present, and patient preferences, including the route of administration they prefer. HCPs should use all these factors to choose the therapy that is going to be best for each patient. And ultimately, the best treatment for patients is the one that they are willing to take.

The updated AGA guidelines for UC take the ever-growing, complicated treatment landscape and narrow it down to make therapy selection less complicated.

Treat-to-Target Strategies in CD
Next, a major theme of the updated AGA guidelines for CD is this movement toward deeper targets. This comes from the STRIDE initiative, which is adopted in the AGA guidelines and informs the recommended treat-to-target measure. What the guidelines took from the STRIDE initiative is that HCPs must treat beyond symptom management in patients with CD. Treat to target includes clinical and endoscopic remission, with the potential of including histologic or transmural healing as well in future guidelines. 

The way HCPs should do this in their real-world practice, without necessarily overtesting patients, is by setting up a strong treatment and monitoring strategy. After risk stratifying patients and choosing the ideal therapy as discussed above, HCPs must develop personalized monitoring goals for each patient. Part of that strategy is getting the baseline assessments needed, such as C-reactive protein, fecal calprotectin, endoscopic assessment, and perhaps an intestinal ultrasound. This is important because HCPs must know what values or results are considered “abnormal” in each patient when they are inflamed and then follow that via monitoring during treatment. Furthermore, by benchmarking each patient, HCPs also can narrow down the monitoring tools needed and stick to the ones that make the most sense for each patient.

When establishing a monitoring strategy, I usually like to outline what the next 6 months or so will look like for each patient. That might mean checking symptoms and assessing patient-reported outcomes in 4 weeks after starting therapy. Four weeks after that, I might do the same check-in but also measure C-reactive protein if that is applicable to the patient. After another 4 weeks, I might check the fecal calprotectin again and check in with the patient as well as other members of the team who are assisting in their care.

Ultimately, 6 months later, I would get an endoscopic assessment of the patient. I want to be 99% sure of what I find via endoscopy because I have been monitoring the patient this whole time. The other importance of monitoring is that it informs one’s ability to make changes to patients’ treatment plan. If they are not hitting the targets with their current therapy, HCPs can circle back and make real-time adjustments based on the outcomes of their monitoring strategy.

Balance Is Key in IBD Management
Managing IBD is all about getting the right treatment to the right patient at the right time. For high-risk patients, that means getting them on advanced therapy as early as possible to maximize early efficacy while also balancing safety. As I mentioned before, finding a balance between efficacy and safety when selecting therapy should consider any present extraintestinal manifestations or comorbidities and patients’ preferences. For those who are incredibly sick with severe disease, HCPs should use their biggest gun—the therapy that is going to work fastest. This is critical because there also is a safety risk if patients do not achieve remission as soon as possible. The true balancing act in IBD is managing patients’ disease, which itself poses a risk, and the safety concerns that you or patients may have about their available therapies.

That said, I believe all IBD agents that are available to us are safe and efficacious to varying degrees. When I consider my treatment sequencing approach, I often do a first pass based on triaging. Are the patients sick enough to warrant either an early TNF antagonist or JAK inhibitor? If they are not, all other applicable classes/agents that are approved by the FDA are on the table.

Withdrawal Strategies in IBD
In treating IBD, HCPs are practicing a lot of combination approaches these days, especially in patients with severe disease. The traditional combination approach is to use a TNF antagonist plus an immunomodulator, but now we are seeing approaches that combine advanced therapies like biologics and/or small molecule agents. Furthermore, ongoing clinical trials are assessing combination approaches with advanced therapies and will inform treatment sequencing in the future. I am sure we will see more data on this presented at the upcoming 2026 Digestive Disease Week.

Regardless, after starting patients on any combination regimen with the goal of deep remission, HCPs face an important decision. Do you have patients stick with their combination regimen or do you withdraw an agent once deep remission is achieved? 

This decision often is easy when following the more traditional approach (a biologic plus an immunomodulator). Per the guidelines, HCPs should always withdraw the immunomodulator first once patients are in remission. That is because we want to preferentially keep the biologic as a treatment. In addition, there is the risk of developing antidrug antibodies to the biologic after withdrawal, so the easy choice is to withdraw the immunomodulator first.

This conversation becomes more interesting when a combination of biologics is used to treat patients. How do you know which agent to withdraw and when to withdraw it? Depending on which therapy patients started first or which one offers the more robust response, these considerations will help you decide which biologic to withdraw. If it were quite difficult to get patients into remission, maybe you would not withdraw either therapy. In this case, HCPs can keep patients on their combination regimen for longer. In turn, if patients are receiving a biologic and small molecule therapy in combination, I would preferentially withdraw the small molecule therapy first because I am not worried about immunogenicity with it. Regardless of which agent is withdrawn first, HCPs must monitor patients closely as they withdraw the second therapy to ensure patients do not take any steps back in terms of their symptoms and disease control.

Your Thoughts
How often do you use a combination therapy of a biologic plus small molecule agent for your patients with IBD? You can get involved in the conversation by answering the poll question and posting a comment below.

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