AGA unveils new clinical practice guideline for Crohn's disease

AGA has rolled out a new living clinical guideline to steer the pharmacologic management of moderate-to-severe Crohn’s disease, prioritizing early use of advanced therapies over step-up strategies that begin with corticosteroids or immunomodulators.

The update was prompted by the approval of new advanced therapies for Crohn’s disease since the publication of the previous AGA guidelines for moderate-to-severe active disease in 2021, according to the guideline’s first author Frank I. Scott, MD, MSCE, of the Crohn’s and Colitis Center and the Division of Gastroenterology and Hepatology at the University of Colorado Anschutz School of Medicine in Aurora.

“These guidelines highlight that there are now multiple treatment options to consider for patients for managing their moderate to severely active Crohn's disease,” Scott told GI & Hepatology News. “We hope that they will help clinicians determine how to maximize the potential benefit of the full armamentarium of therapies available to treat this disease.”

For this guideline update, published in Gastroenterology, a 10-member panel conducted a network meta-analysis to compare 11 medications and used the GRADE framework to evaluate evidence certainty and craft graded clinical recommendations. Of the 16 evidence-based recommendations, the panel rated one as “strong,” nine as “conditional,” and six as “knowledge gaps.” In the guideline, the word recommends denotes a strong recommendation, whereas suggests signifies a conditional one.

Key highlights include the following: 

• AGA recommends infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib, and suggests certolizumab pegol or vedolizumab over no treatment.

• For patients new to advanced therapies, the AGA suggests higher-efficacy agents such as infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab instead of a lower-efficacy medication such as certolizumab pegol or upadacitinib.

• For patients previously treated with advanced therapies, preferred options include higher- or intermediate-efficacy medications such as adalimumab, risankizumab, guselkumab, upadacitinib, ustekinumab, or mirikizumab, rather than a lower-efficacy medication such as vedolizumab or certolizumab pegol.

The guideline panel also advises using combination therapy with a thiopurine when considering using infliximab, and that in individuals who achieve steroid-free remission with such therapy, providers can consider withdrawing the immunomodulator.

“Importantly, these guidelines should be viewed as general recommendations, and we advocate that clinical decisions should be between providers and their patients when making treatment decisions,” Scott noted. “Shared decision-making is critical.”

To make the recommendations easy to use, the guideline offers practice-ready implementation considerations and two clinical decision support tools that help clinicians navigate pharmacologic treatment choices.

Scott noted that the guideline recommendations regarding the withdrawal of immunomodulators in patients receiving combination therapy with an anti-TNF and an immunomodulator who have achieved remission for more than 6 months will likely influence his practice. “This was something I’d often discussed with patients when starting combination therapy, but I think with the significant volume of data supporting this recommendation in these guidelines, I will address this more frequently in appropriate patients,” he said.

Scott added that, unexpectedly, the panel was unable to offer a recommendation regarding treatment to a target of mucosal healing. “This target conceptually makes sense, but prospective clinical trial data supporting this approach, over targeting clinical remission, unfortunately are currently limited,” he explained. “There are several ongoing clinical trials assessing this endpoint, however, and we hope that future versions of these guidelines can make a formal recommendation regarding targeting mucosal healing. The benefit of our living guideline approach is that as these data become available, we will be able to incorporate them more rapidly.”  

The panel identified several critical knowledge gaps, including the role of combination therapy for non-TNF biologics as well as whether targeting endoscopic remission (as opposed to clinical remission) yields additional benefit. They also recognized gaps in the research. For example, “the appropriate timing and frequency of endoscopic evaluation, as well as its relation to clinical outcomes, including medication persistence, maintenance of remission, and reduction of CD-related adverse events is unclear at this time, and there is significant heterogeneity regarding time to achieving endoscopic healing or other structural outcomes,” the panel members wrote. “Understanding not only these temporal associations between treatment duration and structural assessment, but also the factors that might predict an expected earlier or later response is critical; such predictive models would allow clinicians to select the appropriate assessment window and modify current therapies more accurately.”

In contrast to other societal guidelines, the AGA guideline panel “felt it was appropriate to use current state-of-the-art synthesis methods to attempt to provide clinicians with guidance in relation to positioning these therapies in treatment-naïve and treatment-exposed individuals,” they wrote. They also emphasized that the guidelines are living documents that “will be updated quarterly, allowing for rapid evolution as new data become available.”

The guideline highlights the treatment options with the strongest evidence, taking each patient’s prior treatment experience into account. “I think it’s important to emphasize that treatment decisions should be individualized and should involve shared decision-making among providers and their patients,” Scott said. “Patient preferences, age, active comorbidities, and pregnancy considerations should always be considered when selecting the appropriate treatment plan for our patients.” 

Scott disclosed that he has received honoraria from AGA, Crohn's and Colitis Foundation, Medscape/WebMD, and MedPage Today. He has also received research support from the Crohn's and Colitis Foundation.