Translating AGA Guidelines into Practice: Managing Moderate-to-Severe Crohn's Disease

AGA guideline updates shift selection of therapy for moderate-to-severe Crohn's disease away from routine step-up sequencing toward a prior-treatment–informed, comparative-effectiveness approach that favors earlier use of higher-efficacy agents to reduce progression risk.

The guidance reframes sequencing: rather than defaulting to incremental escalation, clinicians are advised to match agent potency to a patient's prior exposures and treatment durability. For patients with prior anti–TNF or vedolizumab exposure, preferred choices move toward non–TNF options with demonstrated effectiveness after that prior therapy, which shortens the interval to biologic or small-molecule initiation when higher efficacy is clinically warranted.

The guideline highlights infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, and upadacitinib as principal options for induction and maintenance, based on comparative effectiveness across trials. Anti–TNF–naive patients who need rapid, high-level response may still preferentially receive anti–TNF therapy; anti–TNF–experienced patients are steered to IL‑12/23 or selective IL‑23 inhibitors or to a JAK inhibitor depending on comorbidity and prior response. These recommendations are integrated with patient-specific factors such as infection risk and prior biologic durability to individualize first-line choices.

Network meta-analysis synthesizes randomized trials to generate a comparative ranking that quantifies relative induction and maintenance remission probabilities and safety trade-offs. Where head-to-head data are lacking, the ranking enables clinicians to compare agents by effect size and expected remission probabilities rather than by class label alone, making relative benefit–risk central to the prescribing decision.