Clinical Guideline Update: Management of Ulcerative Colitis in Adults from updated ACG Clinical Guideline: JAMA | July 2026

Introduction:

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. The updated 2025 American College of Gastroenterology (ACG) Guideline emphasizes treat-to-target management, objective disease monitoring, and individualized selection of advanced therapies to achieve sustained remission.

Why was this guideline needed?

• The therapeutic landscape of UC has expanded with multiple new biologic and oral small-molecule therapies.
• Treatment goals have evolved beyond symptom control to include endoscopic healing and steroid-free remission.
• Biomarker-guided monitoring is increasingly replacing symptom-based assessment alone.
• Updated evidence was required to guide sequencing of advanced therapies.
• Standardized recommendations are needed for both outpatient and hospitalized patients.

Key Takeaways:

• Exclude Clostridioides difficile infection in all patients with suspected UC and in every patient hospitalized with acute severe UC before initiating treatment.
• Fecal calprotectin is the preferred noninvasive biomarker for monitoring disease activity, treatment response, and detecting relapse, reducing reliance on repeated colonoscopy.
• Rectal 5-ASA (1 g/day) remains first-line therapy for mild ulcerative proctitis, while combined oral and rectal 5-ASA is recommended for left-sided disease.
• Systemic corticosteroids should be used only for induction of remission and must not be continued for maintenance because of long-term toxicity.
• Patients with moderate-to-severe UC should receive advanced therapies including anti-TNF agents, vedolizumab, ustekinumab, IL-23p19 inhibitors (guselkumab, mirikizumab, risankizumab), JAK inhibitors, or S1P receptor modulators, with treatment individualized according to disease characteristics, comorbidities, safety profile, extraintestinal manifestations, and patient preference.
• Infliximab should be combined with a thiopurine when appropriate to reduce immunogenicity and improve drug durability.
• Vedolizumab offers gut-selective immunosuppression with an excellent safety profile, making it particularly attractive for patients at higher risk of systemic infections.
• Acute severe UC requires hospitalization, intravenous corticosteroids, and early assessment of steroid response. Patients with steroid-refractory disease should receive infliximab or cyclosporine as rescue therapy.
• Oral advanced therapies (JAK inhibitors and S1P receptor modulators) provide rapid symptom control but require careful monitoring for infections and class-specific adverse effects, including herpes zoster and cardiovascular events.
• Treatment selection should be individualized through shared decision-making, considering disease severity, previous biologic exposure, route of administration, safety, cost, and patient preferences.

Clinical Impact:

The updated ACG guideline reinforces a treat-to-target strategy centered on objective inflammation control, steroid-free remission, and early use of effective advanced therapies. Routine use of fecal calprotectin, prompt optimization of therapy, and individualized biologic or small-molecule selection are now central to modern UC management.

Bottom Line:

The 2025 ACG guideline shifts ulcerative colitis management toward personalized, biomarker-driven care. Fecal calprotectin-guided monitoring, avoidance of long-term corticosteroids, and timely use of biologics or advanced oral therapies are the key principles for achieving durable remission and improved long-term outcomes.