Summary

ACG 2025 update to the 2019 UC guideline addresses diagnosis, disease activity assessment, induction/maintenance therapy across mild to severe UC, positioning of newer biologics and small molecules (S1P modulators, JAK inhibitors, IL-23p19 inhibitors), and management of acute severe UC. New features include a defined role for intestinal ultrasound, an updated ACG UC Disease Activity Index, a positioning/sequencing section, and incorporation of bowel urgency as a key patient-reported outcome. Histologic remission is acknowledged as prognostic but not a required target; treat-to-target emphasizes endoscopic improvement (MES 0-1) plus symptomatic remission.

Key Recommendations

Confirm UC diagnosis with full colonoscopy and ileal intubation plus biopsies of both inflamed and endoscopically normal mucosa (including rectum); use flexible sigmoidoscopy in severe disease to reduce perforation risk.
Test for C. difficile in all patients with new UC diagnosis or flare/hospitalization; treat positive cases with vancomycin or fidaxomicin per IDSA.
For mildly-to-moderately active proctitis or left-sided UC, use rectal 5-ASA first-line; combine with oral 5-ASA ≥2 g/day for left-sided disease; oral 5-ASA monotherapy for extensive mild-to-moderate UC.
Do not switch 5-ASA formulations after failure; escalate to budesonide MMX 9 mg or systemic steroids, then advanced therapy.
Do not use corticosteroids, thiopurines, or methotrexate for induction or as monotherapy maintenance in moderate-to-severe UC; treat moderate-to-severe UC with anti-TNF, vedolizumab, ustekinumab, IL-23p19 inhibitors (guselkumab, mirikizumab, risankizumab), S1P modulators (ozanimod, etrasimod), or JAK inhibitors (tofacitinib, upadacitinib).
Use infliximab + azathioprine combination over monotherapy in biologic-naive moderate-to-severe UC; vedolizumab is superior to adalimumab head-to-head and preferred in TNF-naive patients.
Per US FDA labeling, position tofacitinib and upadacitinib after anti-TNF failure; use lowest effective maintenance dose and caution with CV/VTE risk factors.
Stop 5-ASA when advancing to biologic or JAK inhibitor — no efficacy benefit and not cost-effective to continue.
Hospitalize ASUC patients; give IV corticosteroids, VTE prophylaxis with low molecular weight heparin, avoid NSAIDs/opioids/anticholinergics/antibiotics (unless infection); assess response by day 3-5 and initiate rescue therapy (infliximab or cyclosporine) or colectomy if no response.
In ASUC with low albumin (<2.5 g/dL), consider intensified infliximab dosing (10 mg/kg); choose between cyclosporine and infliximab based on provider experience and prior immunomodulator exposure.
Apply treat-to-target: assess symptomatic remission plus endoscopic improvement (MES ≤1) every 3 months during active disease; use fecal calprotectin and CRP as surrogate monitoring tools.
Refer for colectomy in ASUC with toxic megacolon, perforation, hemorrhage, multiorgan dysfunction, or failure to respond to 3-5 days of IV steroids and rescue therapy; do not delay surgery.

Thresholds & Doses

Proctitis (E1): inflammation ≤15 cm; left-sided (E2): up to splenic flexure; extensive (E3): proximal to splenic flexure (Montreal).
Truelove-Witts severe UC: >6 BMs/day plus fever, tachycardia, Hgb <10.5 g/dL, or ESR >30 mm/hr.
PUCAI ≥65 defines pediatric ASUC; PUCAI >45 at day 3 or >70 at day 5 predicts IV steroid failure.
Oxford criteria: >8 BMs on day 3 of IV steroids, or 3-8 BMs with CRP >45 mg/L → 85% colectomy risk.
Fecal calprotectin: <50-60 μg/g suggests deep remission; <187 μg/g predicts mucosal healing; >321 μg/g in clinical remission predicts relapse.
Oral 5-ASA induction: ≥2 g/day (up to 4.8 g/day for moderate); maintenance ≥2 g/day; once-daily dosing equivalent to divided dosing.
Rectal 5-ASA: 1 g/day enema or suppository.
Budesonide MMX: 9 mg/day × 8 weeks for mild-to-moderate UC.
Prednisone induction: 40-60 mg/day; taper over 8-12 weeks; no benefit beyond 60 mg methylprednisolone equivalent.
Infliximab: 5 mg/kg IV at 0, 2, 6 weeks then every 8 weeks; consider 10 mg/kg in ASUC if albumin <2.5 g/dL.
Adalimumab: 160 mg SC week 0, 80 mg week 2, then 40 mg every 2 weeks.
Golimumab: 200/100 mg induction then 100 mg SC every 4 weeks maintenance (preferred over 50 mg).
Vedolizumab: 300 mg IV at 0, 2, 6 weeks then every 8 weeks; SC 108 mg every 2 weeks for maintenance.
Tofacitinib: 10 mg PO BID induction × 8 weeks (extend to 16 weeks if no response); maintenance 5 or 10 mg BID (10 mg preferred in TNF-experienced).
Upadacitinib: 45 mg PO daily × 8 weeks induction; 15 or 30 mg daily maintenance (30 mg in TNF-experienced).
Ozanimod: 0.92 mg PO daily (after titration); contraindicated with significant CV disease, untreated sleep apnea, conduction defects, MAOI use.
Etrasimod: 2 mg PO daily (includes proctitis indication).
Ustekinumab: ~6 mg/kg IV induction, then 90 mg SC every 8 weeks.
Mirikizumab: 300 mg IV every 4 weeks × 3 induction, then 200 mg SC every 4 weeks.
Guselkumab: 200 mg IV at 0, 4, 8 weeks, then 100 mg SC q8w or 200 mg SC q4w.
Risankizumab: 1200 mg IV every 4 weeks × 3 induction, then 180 or 360 mg SC every 8 weeks.
Cyclosporine ASUC rescue: 2 mg/kg IV (target level 200-400 ng/mL); transition to thiopurine maintenance.
Tacrolimus: oral target trough 10-15 ng/mL; rectal 2 mg suppository daily for refractory proctitis.
Malnutrition definitions: weight loss >10-15% in 6 months, BMI <18.5 kg/m², or albumin <30 g/L.
Toxic megacolon: transverse colon diameter >5.5 cm on plain film.

Citations

Diagnosis, Assessment, Monitoring, and Prognosis of UC — endoscopic diagnostic approach, Montreal classification, biopsy strategy
Table 4 / ACG UC Disease Activity Index — updated activity stratification incorporating PROs, labs, and endoscopy
Table 8 — poor prognostic factors (extensive colitis, deep ulcers, steroid need, age <30, elevated CRP/ESR, prior hospitalization)
Management of Mildly to Moderately Active UC — 5-ASA dosing, combination oral+rectal, budesonide MMX
Management of Moderately to Severely Active UC — induction/maintenance recommendations across biologic and small molecule classes
Positioning Considerations section — sequencing of advanced therapies, EIM-based choice, stopping 5-ASA after escalation
Management of Hospitalized Patient with ASUC / Figure 3 algorithm — IV steroids, rescue therapy choice, VTE prophylaxis, colectomy indications
Goals for Managing Patients with UC / STRIDE-II — treat-to-target with MES 0-1 and symptomatic remission every 3 months