AGA Living Clinical Practice Guideline on the...

AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

Abstract

BACKGROUND & AIMS: This American Gastroenterological Association (AGA) living guideline is intended to support practitioners in the pharmacologic management of moderate-to-severely active Crohn's disease (CD). METHODS: A multidisciplinary panel of clinical experts and methodologists used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations. RESULTS: The guideline panel agreed on 16 recommendations, of which 1 is a strong recommendation, 9 are conditional recommendations, and 6 were identified as knowledge gaps. In adult patients with moderate-to-severely active CD, the AGA recommends the use of infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment, and suggests the use of certolizumab pegol or vedolizumab over no treatment. In individuals who are naïve to advanced therapies, the AGA suggests using a higher efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab) rather than a lower-efficacy medication (certolizumab pegol or upadacitinib). In individuals who have previously been exposed to 1 or more advanced therapies, the AGA suggests using a higher efficacy medication (adalimumab, risankizumab, guselkumab, or upadacitinib) or intermediate efficacy medication (ustekinumab or mirikizumab) rather than a lower efficacy medication (vedolizumab or certolizumab pegol). In adult outpatients with moderate-to-severely active CD, the AGA suggests against using thiopurine monotherapy for induction of remission, but suggests using thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission. The AGA suggests using subcutaneous methotrexate for induction and maintenance of remission, but suggests against using oral methotrexate. The AGA suggests using combination therapy with infliximab and thiopurines over infliximab monotherapy, particularly in those naïve to thiopurines. The AGA also suggests using initial advanced therapy over step therapy involving corticosteroids and/or immunomodulators in patients with moderate-to-severely active CD. The panel also proposed key implementation considerations for optimal use of these medications, identified several knowledge gaps, and areas for future research. CONCLUSIONS: This guideline provides a comprehensive, patient-centered, evidence-based approach to the pharmacologic management of patients with moderate-to-severely active CD.

Authors

Scott FI; Ananthakrishnan AN; Click B; Agrawal M; Syal G; Haydek JP; Yuan Y; Kappelman MD; Lewis JD; Singh S

Journal

Gastroenterology, Vol. 169, No. 7, pp. 1397–1448

Publisher

Elsevier

Publication Date

December 1, 2025

DOI

10.1053/j.gastro.2025.09.038

ISSN

0016-5085

Associated Experts

Yuhong Yuan

Assistant Professor (Part-Time), Faculty of Health Sciences

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