The Ulcerative Colitis Playbook Just Got a Major Rewrite
Here's a summary of the key updates and new elements in the ACG Clinical Guideline Update: Ulcerative Colitis in Adults
Increased Complexity of Management: The guideline acknowledges the growing complexity of UC management, which has been exacerbated by the increasing availability of additional treatments and therapeutic classes over the past five years. This reflects the evolving landscape of UC therapies.
Focus on New Approaches and Evidence: This update specifically incorporates new approaches and evidence for the treatment and prevention of complications. The rationale is to ensure that the guidelines remain current and relevant in light of emerging scientific data.
Positioning and Sequencing Therapies: A new section reviews the evidence and considerations for positioning and sequencing therapies. This addition is due to the increased number of available therapies for UC. The guideline prioritizes direct evidence over secondary levels of evidence, such as meta-analyses, in its recommendations for therapy positioning.
Defined Role for Intestinal Ultrasound (IUS): A significant new element is the defined role for IUS as a tool to measure UC disease activity and monitor response to therapy or disease relapse. The rationale is that IUS is a non-invasive, point-of-care test that can detect bowel wall thickness, hyperemia, and other parameters of active colitis, and it can also detect a response to therapy as early as 2 weeks.
Updated Disease Activity Index: The ACG UC Disease Activity Index has been updated, incorporating patient-reported outcomes (PROs) (e.g., bleeding, stool frequency, urgency), inflammatory burden markers (e.g., FC, CRP, serum albumin), disease course (e.g., hospitalization, steroid need, medication non-response), and disease impact (HRQoL and social functioning). This comprehensive approach aims to guide treatment decisions based on a more holistic view of disease severity.
Specific US Environmental Concerns: The guidelines are tailored to address specific concerns and challenges within the US environment.
Stronger Stance on Third-Party Payers: The guideline explicitly advises that third-party payers and step therapy requirements should not interfere with the patient and clinician in making treatment decisions. The rationale is to advocate for the preservation of the doctor-nurse-patient relationship and shared decision-making, to improve quality of life and prevent economic hardships or delayed treatments.
Emphasis on Earlier Advanced Treatment: There is an emphasis on treating patients with moderately to severely active UC, especially those with a high risk of hospitalization or colectomy, with therapies proven effective for these conditions earlier in their disease course. The rationale is that patients have higher rates of response and remission with their first therapies compared to those who have failed one or more other advanced therapies.
Specific Recommendations for New Therapies: The guideline includes new recommendations for several advanced therapies:
S1P receptor modulators (ozanimod and etrasimod) for the induction of remission in moderately to severely active UC. These agents sequester activated lymphocytes in lymph nodes, decreasing cellular inflammation. Clinical trials demonstrated their efficacy in inducing and maintaining remission.
IL-12/23p40 antibody (ustekinumab) for induction and maintenance of remission in moderately to severely active UC. Clinical trials showed its superiority over placebo in achieving clinical remission and endoscopic improvement.
IL23p19 inhibitors (guselkumab, mirikizumab, or risankizumab) for induction and maintenance of remission in moderately to severely active UC. Studies like QUASAR, LUCENT, and INSPIRE demonstrated their efficacy in inducing clinical and endoscopic remission.
JAK inhibitors (tofacitinib and upadacitinib) for induction and maintenance of remission in moderately to severely active UC. Pivotal trials (OCTAVE, U-ACHIEVE, U-ACCOMPLISH) showed their effectiveness in achieving clinical and endoscopic remission.
Guidance on Discontinuing 5-ASA with Advanced Therapies: The guideline suggests against using concomitant 5-ASA for added clinical efficacy in patients with moderately to severely active UC who have failed 5-ASA and are now on advanced therapies like biologics or JAK inhibitors. This is based on analyses indicating no benefit to continuation and no harm to stopping 5-ASA in these settings, and cost-effectiveness evaluations.
Updated Acute Severe Ulcerative Colitis (ASUC) Management Algorithm: Figure 3 provides an updated algorithm for managing hospitalized patients with ASUC. This reflects current best practices for managing this critical condition.
Guidance on JAK Inhibitors in ASUC: While acknowledging promising emerging data for tofacitinib and upadacitinib in ASUC, the guideline cautions against routine recommendation as a standard option for all patients at this time. This is because current studies are either uncontrolled, in populations without prior anti-TNF exposure, or use off-label dosing of the medications. Clinicians are advised against using higher doses of JAK inhibitors in combination with corticosteroids or as rescue therapy immediately after infliximab due to concerns about over-immunosuppression and opportunistic infections.
Citation
Rubin, David T. MD, FACG1; Ananthakrishnan, Ashwin N. MBBS, MPH, FACG2; Siegel, Corey A. MD, MS3; Barnes, Edward L. MD, MPH, FACG4; Long, Millie D. MD, MPH, FACG4. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. | DOI: 10.14309/ajg.0000000000003463
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