The AGA released a living guideline for moderate-to-severe Crohn’s disease (published in Gastroenterology, Dec 2025) that pushes clinicians toward earlier use of high-efficacy “advanced” therapies (biologics/small molecules) rather than waiting through insurance-driven step therapy.
Key takeaways:
- Early high-efficacy advanced therapy is favored to help prevent disease progression.
- For advanced-therapy–naïve adults, AGA recommends using agents like infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib (and suggests certolizumab pegol or vedolizumab over no treatment).
- It stratifies drugs into efficacy “buckets” (higher vs lower for naïve; higher/intermediate/lower for previously exposed) to guide sequencing.
- Thiopurine monotherapy: suggested against for induction; may be used for maintenance (often after steroid-induced remission).
- Methotrexate: guideline favors subcutaneous methotrexate; suggests against oral methotrexate.
- Combination therapy: suggests infliximab + thiopurine over infliximab alone (especially if thiopurine-naïve).
- A notable “gap”: the panel couldn’t recommend for/against treat-to-target mucosal (endoscopic) healing due to limited prospective trial evidence—despite this being common in practice and supported by other consensus/guidelines.