2025 AGA Pharmacologic Management of Crohn's Disease Guideline Update — 16 Recommendations Included

The American Gastroenterological Association (AGA) just released an update to its living clinical practice guideline on the pharmacological management of moderate-to-severe Crohn’s disease. The 16 guideline recommendations featured in the 2025 update focus on the use and positioning of advanced therapies, the use of immunomodulators, combination therapy of biologics and immunomodulators, de-escalation of therapy, early advanced therapy, and treating to endoscopic remission compared to clinical remission.

With the 16 key recommendations summarized below, we’re providing a quick look at each recommendation to help you understand what’s included in the 2025 update. Refer to the guideline summary or the full text version of the guideline update for the most thorough explanation of these recommendations, along with their levels of evidence and implementation considerations.

Recommendations from the AGA 2025 Pharmacological Management of Moderate-to-Severe Crohn’s Disease Living Clinical Practice Guideline

• Recommendations 1 and 2: The AGA recommends infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment, and suggests the use of certolizumab pegol or vedolizumab, over no treatment, in adult outpatients with moderate-to-severely active Crohn’s disease.
• Recommendation 3: For adult outpatients with moderate-to-severely active Crohn’s disease who are naive to advanced therapies, the AGA suggests using a higher-efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) rather than a lower-efficacy medication (certolizumab pegol, upadacitinib).
• Recommendation 4: The AGA suggests using a higher-efficacy medication (adalimumab, risankizumab, guselkumab, upadacitinib) or an intermediate-efficacy medication (ustekinumab, mirikizumab) rather than a lower-efficacy medication (vedolizumab, certolizumab pegol) in adult outpatients with moderate-to-severely active Crohn’s disease who previously were exposed to one or more advanced therapies, particularly TNF antagonists.
• Recommendation 5: The AGA suggests against the use of thiopurines monotherapy over no treatment for inducing remission in adult outpatients with moderate-to-severely active Crohn’s disease.
• Recommendation 6: For adult outpatients with moderate-to-severely active Crohn’s disease who achieved remission, the AGA suggests thiopurine monotherapy over no treatment for maintaining remission.
• Recommendation 7: The use of subcutaneous or intramuscular methotrexate monotherapy is suggested by the AGA over no treatment for adult patients with moderate-to-severely active Crohn’s disease.
• Recommendation 8: For adult outpatients with moderate-to-severely active Crohn’s disease, the AGA suggests against oral methotrexate monotherapy over no treatment.
• Recommendation 9: The AGA suggests using infliximab in combination with thiopurines rather than infliximab monotherapy for adult outpatients with moderate-to-severely active Crohn’s disease who are naive to thiopurines and starting infliximab.
• Recommendation 10: For adult outpatients with moderate-to-severely active Crohn’s disease, the AGA provides no recommendation regarding using infliximab in combination with methotrexate over infliximab monotherapy.
• Recommendation 11: No recommendation is provided by the AGA for adult outpatients with moderate-to-severely active Crohn’s disease regarding the use of adalimumab in combination with thiopurines or methotrexate over adalimumab monotherapy. 
• Recommendation 12: The AGA makes no recommendation in favor of, or against, using non-TNF-targeting biologics (vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) in combination with thiopurines or methotrexate or corresponding biologic monotherapy for adult outpatients with moderate-to-severely active Crohn’s disease.
• Recommendation 13: The AGA suggests withdrawing the immunomodulator in adult outpatients with moderate-to-severely active Crohn’s disease who are in a corticosteroid-free clinical remission for at least six months on combination therapy with TNF antagonists and an immunomodulator.
• Recommendation 14: For adult outpatients with moderate-to-severely active Crohn’s disease who are in corticosteroid-free clinical remission for at least six months on combination therapy of TNF antagonists and an immunomodulator, the AGA suggests against the withdrawal of the TNF antagonist.
• Recommendation 15: The AGA suggests the upfront use of advanced therapy compared with step-up therapy with initial use of corticosteroids and/or immunomodulator monotherapy for adult outpatients with moderate-to-severely active Crohn’s disease.
• Recommendation 16: The AGA has no recommendation in favor of, or against, treating to a target of endoscopic remissions, compared with treating to a target of symptomatic remission in adult outpatients with moderate-to-severely active Crohn’s disease.

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