The American Gastroenterological Association (AGA) has issued updated guidelines for managing moderate-to-severe ulcerative colitis, reflecting advances since its 2020 recommendations. Published in Gastroenterology, the guidelines incorporate evidence from seven new therapeutic agents approved since 2020.

The panel, led by Siddharth Singh, MD, from the University of California, San Diego, issued 14 recommendations based on a systematic review through November 2023, using the GRADE framework.

Key Recommendations for Biologic-Naïve Patients

The guidelines recommend advanced therapies—including infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, and guselkumab—as first-line options for moderate-to-severe ulcerative colitis (UC). Intermediate-efficacy drugs like golimumab, ustekinumab, tofacitinib, filgotinib, and mirikizumab are suggested when high-efficacy drugs are less suitable. Adalimumab, categorized as lower-efficacy, is less preferred in this context.

Recommendations for Biologic-Exposed Patients

Patients previously treated with advanced therapies, particularly TNF antagonists, are encouraged to use high-efficacy options (e.g., tofacitinib, upadacitinib, ustekinumab) or intermediate-efficacy choices (e.g., risankizumab, guselkumab). Lower-efficacy treatments like adalimumab and vedolizumab may require prolonged durations for effectiveness in these cases.

Safety Considerations

Key safety findings highlighted include:

• Vedolizumab reduced infection risk by 32% compared with TNF antagonists.
• Elevated lymphoma risk with TNF antagonists (0.41 per 1000 person-years) compared to unexposed patients (0.26 per 1000 person-years).

Patient-specific factors including age, comorbidities, and cardiovascular risks are critical in therapy selection, particularly with JAK inhibitors. Pre-treatment protocols include hepatitis B and tuberculosis screening and vaccinations for influenza, pneumococcal pneumonia, and herpes zoster.

Extended Induction Strategies

For severe cases, extended induction regimens may improve outcomes. Notably, 48% of upadacitinib non-responders achieved response with an additional eight weeks of induction, and 29% of patients de-escalated from tofacitinib required dose re-escalation.

Implementation and Monitoring

The guidelines outline specific monitoring:

• Symptomatic response: within 3 months
• Biochemical remission: at 3 to 6 months
• Endoscopic improvement/remission: at 6 to 12 months

Patient selection focuses on those with stool frequency and rectal bleeding scores ≥2. Hospitalized patients with acute severe UC were excluded from these recommendations.

Living Guidelines Framework

Structured as living guidelines, updates will occur every six months to reflect phase 3 or 4 data on newly approved therapies and emerging safety findings.

These recommendations represent a shift toward earlier use of personalized, high-efficacy therapies, prioritizing patient-specific factors and minimizing delays in effective treatment.

A full list of conflicts can be accessed at AGA’s National Office in Bethesda, MD.