Ulcerative Colitis

See Inflammatory Bowel Disease for shared epidemiology, classification, clinical features, and diagnosis. This page covers UC-specific medical management, acute severe UC, and surgical indications/options. The medical-management and ASUC sections below are sourced from a 2025 ACG society guideline (ACG 2025 - Ulcerative Colitis Guideline) — GRADE-based recommendations plus expert-consensus statements, one tier more authoritative than a single trial but not independently re-verified against each underlying trial. The surgical-options section remains sourced from the textbook reference chapter (Sabiston Ch52 - Inflammatory Bowel Disease).

Disease severity and monitoring

Beyond the extent-based classification on Inflammatory Bowel Disease (proctitis/left-sided/ extensive), the ACG guideline layers in a severity framework: the ACG UC Disease Activity Index combines patient-reported outcomes (stool frequency, bleeding, urgency), labs (hemoglobin, ESR, CRP, fecal calprotectin), and endoscopy (Mayo endoscopic subscore or UCEIS) into remission/mild/moderate-severe/fulminant tiers — more multidimensional than the Truelove and Witts criteria referenced on Inflammatory Bowel Disease.

Treatment goal is endoscopic improvement (Mayo endoscopic subscore 0–1), not symptomatic remission alone — endoscopically healed mucosa correlates with sustained steroid-free remission and lower colectomy risk. “Deep remission” = symptomatic remission + endoscopic healing. Fecal calprotectin is a validated tool for both diagnosis and ongoing monitoring (response to therapy, suspected relapse, maintenance surveillance). Intestinal ultrasound is a newly endorsed point-of-care monitoring adjunct (pooled sensitivity 85%, specificity 92% vs. endoscopy/biomarkers), though US credentialing pathways are still maturing.

Medical management

Stepwise, extent- and severity-guided. See Inflammatory Bowel Disease for the shared drug-class table (mechanism, route); this section adds UC-specific dosing, sequencing, and trial evidence.

Mildly to moderately active UC:

• Topical (rectal) 5-ASA preferred first-line for proctitis/left-sided disease over topical corticosteroids. Oral 5-ASA ≥2.0 g/d for extensive colitis. Combination oral + rectal 5-ASA outperforms oral alone for left-sided disease. No benefit to dose-escalating 5-ASA beyond ~2.4 g/d in low-activity disease.
• Budesonide MMX 9 mg/d for 5-ASA nonresponders or 5-ASA-intolerant patients.
• Oral corticosteroids if 5-ASA fails outright, or for any extent of UC not responding to 5-ASA.
• Probiotics and fecal microbiota transplant: insufficient evidence to recommend as primary induction therapy at this time.

Moderately to severely active UC — advanced therapy roster (this is genuinely new to the wiki; previously only the bare drug-class table on Inflammatory Bowel Disease existed with no UC-specific positioning or trial evidence):

Class	Agents	Notes
Anti-TNF	Infliximab, adalimumab, golimumab	Infliximab explicitly preferred — observational data suggest better long-term outcomes and lower postop-complication association than adalimumab. Combination with a thiopurine (azathioprine) recommended when infliximab is used.
Anti-integrin	Vedolizumab	Head-to-head RCT (VARSITY) vs. adalimumab: vedolizumab superior for clinical remission (31.3% vs 22.5%) and endoscopic improvement (39.7% vs 27.7%) at 52 weeks — guideline recommends vedolizumab over adalimumab on this basis. Preferred when infection risk is a concern (gut-selective mechanism).
Anti-IL-12/23	Ustekinumab	UNIFI trial.
Anti-IL-23p19	Guselkumab, mirikizumab, risankizumab	Newer class; all strong/moderate recommendations for induction and maintenance.
JAK inhibitors	Tofacitinib, upadacitinib	Upadacitinib induction is the single highest evidence-quality rating in the guideline (high). US label restricts use to after anti-TNF failure, driven by the ORAL SURVEILLANCE rheumatoid-arthritis safety trial (increased MACE/cancer/VTE with tofacitinib vs. a TNF inhibitor) — a signal from a different disease population, not directly replicated in the UC trials themselves. Filgotinib available in Europe, not the US.
S1P receptor modulators	Ozanimod, etrasimod	Newer oral small-molecule class (ELEVATE UC 52/12 trials).

No head-to-head trials exist between most of these classes; the ACG guideline explicitly declines to use network meta-analysis/indirect comparisons to rank them, except where real RCT data exists (vedolizumab vs. adalimumab, above). Agent choice in practice is guided by prior anti-TNF exposure, infection risk, extraintestinal manifestations (choose an agent effective at both gut and joint/skin sites), and avoiding payer-driven step therapy. On secondary loss of anti-TNF response, reactive therapeutic drug monitoring (trough levels + antidrug antibodies) is recommended; routine proactive TDM in all patients is not yet evidence-supported.

Efficacy positioning — a genuine disagreement between guidelines

ACG 2025 - Ulcerative Colitis Guideline (above) explicitly declines to rank therapies by network meta-analysis (NMA). AGA 2024 - Moderate-to-Severe UC Pharmacotherapy Guideline does the opposite — it builds an explicit “higher/intermediate/lower efficacy” bucket system substantially from NMA p-scores, on the reasoning that with 11+ approved agents and few head-to-head trials, some positioning guidance beats none. Both approaches are legitimate GRADE-consistent choices, not an error in either guideline, but they are not simply additive — treat the two guidelines’ positioning tables as reflecting different evidentiary philosophies, not different snapshots of the same ranking. The AGA buckets:

Population	Higher efficacy	Intermediate efficacy	Lower efficacy
Advanced-therapy-naive	Infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab	Golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab	Adalimumab
Prior advanced-therapy exposure (esp. anti-TNF)	Tofacitinib, upadacitinib, ustekinumab	Filgotinib, mirikizumab, risankizumab, guselkumab	Adalimumab, vedolizumab, ozanimod, etrasimod

Note vedolizumab moves from the higher bucket (naive) to the lower bucket (biologic-exposed) — these are population-specific buckets, not a fixed drug ranking. Both guidelines agree on the one real head-to-head data point (VARSITY: vedolizumab > adalimumab) and both treat infliximab and upadacitinib favorably; the AGA’s added granularity is the population-specific bucket-flipping the ACG guideline deliberately avoided producing.

Combination therapy, de-escalation, and sequencing (AGA 2024)

• Infliximab + immunomodulator (thiopurine) is recommended over either agent alone — direct trial evidence from the UC-SUCCESS trial: corticosteroid-free remission 39.7% (combination) vs. 22.1% (infliximab alone) vs. 23.7% (azathioprine alone) at week 16; mucosal healing 62.8% vs. 54.6% vs. 36.8%. Adalimumab or golimumab + immunomodulator is also recommended over monotherapy, though this is extrapolated from TNF-class mechanism similarity and Crohn’s-trial evidence (SONIC) rather than a UC-specific RCT for those two agents. No recommendation (knowledge gap) for combining immunomodulators with non-TNF biologics — no clear benefit shown, unlike the TNF class. Trade-off: combination therapy carries higher lymphoma risk than TNF-antagonist monotherapy (HR 2.53) or thiopurine monotherapy (HR 2.35) in observational French national data, without a matching serious-infection increase.
• De-escalation (a topic the ACG 2025 guideline does not address at all): suggests against withdrawing the TNF antagonist after ≥6 months of corticosteroid-free remission on TNF + immunomodulator combination therapy — withdrawal roughly doubles relapse risk at 12 months (31.5% vs. 11.2%). No recommendation on withdrawing the immunomodulator instead while continuing the biologic (knowledge gap; underlying trial data mostly drawn from Crohn’s populations).
• 5-ASA discontinuation on escalation: once a patient has escalated to immunomodulators/advanced therapy after 5-ASA failure, suggests stopping 5-ASA (no treatment-effect modification found in a pooled 10-RCT, 6044-patient analysis) — except patients with residual proctitis, who may still benefit from adding rectal 5-ASA.
• Step therapy: suggests early use of advanced therapy over gradual step-up once a patient meets moderate-to-severe criteria — with an explicit shared-decision caveat that patients who weight 5-ASA’s safety profile highly may reasonably choose gradual step therapy instead.
• Pregnancy (also outside ACG 2025’s scope): avoid JAK inhibitors and S1P receptor modulators in women of childbearing age contemplating pregnancy (limited safety data); TNF antagonists/other biologics have reassuring large-registry (PIANO) data.

Acute severe UC (ASUC)

Defined as ≥6 bowel movements/day plus ≥1 systemic toxicity sign (tachycardia, fever, hemoglobin <10.5 g/dL, or elevated inflammatory markers/CRP). Management algorithm (ACG 2025 Fig. 3):

• Day 0: baseline stool studies including C. difficile; flexible sigmoidoscopy within 72h (preferably 24h) for severity assessment and CMV biopsy; assess for toxic megacolon; VTE prophylaxis; hold 5-ASA (risk of paradoxical diarrhea). Treat CDI (fidaxomicin or vancomycin) or CMV (ganciclovir/valacyclovir) if positive — without withholding UC-directed therapy. If both negative: start IV corticosteroids without delay (methylprednisolone ≤60 mg/d or hydrocortisone 100 mg 3–4×/day).
• Day 3: reassess. Responding (<4 BM/day for 2 days, no bleeding) → transition to oral prednisone 40 mg, manage as outpatient. Not responding → escalate to IV cyclosporine (2–4 mg/kg, target trough 150–250 ng/mL) or infliximab (5 mg/kg, or 10 mg/kg if low albumin) or (emerging, off-label, explicitly flagged as under investigation rather than a formal recommendation) tofacitinib/upadacitinib.
• Day 6: reassess again. Response → maintain on whichever rescue agent worked. No response, or development of toxic megacolon/perforation/severe refractory hemorrhage → surgery.
• Choice between infliximab and cyclosporine rescue is based on provider/institutional familiarity, prior immunomodulator/anti-TNF exposure, and serum albumin — thiopurine-naive patients starting cyclosporine have lower subsequent colectomy risk than thiopurine-exposed/-failed patients.
• Important correction to older surgical teaching: neither infliximab nor cyclosporine rescue therapy increases postoperative complications of colectomy, and necessary surgery should not be delayed for a biologic “washout” period out of concern for this. Delayed surgery is independently associated with worse postoperative outcomes — early surgical consultation/referral is recommended proactively, not reserved as a last resort.
• Nutrition: enteral feeding preferred over bowel rest/TPN (no RCT benefit shown for bowel rest). Malnutrition (weight loss >10–15%/6mo, BMI <18.5, albumin <30 g/L) should be corrected before colectomy where feasible.
• Preferred surgery for ASUC remains subtotal/total colectomy with end ileostomy (not one-stage restorative proctocolectomy) — matches the surgical-options section below; pouch construction is deliberately deferred to a later, better-optimized stage.

Indications for surgery

• Failure to respond to maximal medical therapy — the most common indication. Ranges from patients with poor quality of life (urgency, tenesmus, poor nutritional status, “failure to thrive”) to more acute failure.
• Fulminant colitis — hospitalized, on IV steroids, sometimes in-hospital biologics or IV cyclosporine as an attempt to avoid colectomy (see “Acute severe UC (ASUC)” above for the current ACG-guideline-based escalation algorithm and timing). Toxic megacolon may be present: defined as 3 or more of {tachycardia >100, leukocytosis >12,000/dL, hypoalbuminemia <3 g/dL, temperature

  38°C} plus transverse colon diameter >5 cm on plain film. Note: a “megacolon” alone (dilation without toxicity) does not meet the definition — both toxicity criteria and dilation are required. Colonic perforation risk is significant when this develops.

• Significant GI hemorrhage — an indication for urgent surgery in a minority of cases; frequency of this indication has decreased over time.
• Failure to grow — indication in children.
• Dysplasia or cancer — colectomy indicated. Patients with longstanding UC (>8 years) are at high risk of dysplasia/cancer, more so with concurrent sclerosing cholangitis (see Inflammatory Bowel Disease); regular (yearly) surveillance colonoscopy with or without chromoendoscopy (spraying methylene blue/indigo carmine to highlight dysplastic mucosa for targeted biopsy, vs. the older random-biopsy protocol) is recommended after 8 years of disease. “Flat” dysplasia is harder to detect than “polypoid” dysplasia, which can sometimes be managed with polypectomy and continued surveillance if isolated. Multiple areas of flat dysplasia, or any high-grade dysplasia, is an indication for colectomy.
• Severe extraintestinal disease not responding to medical therapy is an indication in some patients, though some extraintestinal manifestations run a course independent of the colon.

Surgical options

• Total proctocolectomy with end ileostomy (subtotal colectomy + ileostomy + Hartmann’s approach) — treatment for fulminant colitis not responding to maximal medical therapy. A known complication is “blow-out” of the Hartmann stump leading to a pelvic abscess; avoided by leaving a long Hartmann stump incorporated into the fascial closure or extraction site, with the skin left open (a controlled mucous fistula rather than a deep pelvic infection). Restoration of continuity is typically deferred ~3 months, once the patient is stabilized and weaned off immunosuppression.
• Subtotal colectomy with ileorectal anastomosis — avoids pelvic dissection entirely (so avoids the sexual dysfunction/fertility risks of pelvic dissection). Best suited to patients with limited rectal involvement, which is uncommon in UC (disease is usually worst distally). Retained rectum requires ongoing dysplasia surveillance.
• Ileal Pouch–Anal Anastomosis (IPAA) — the most popular procedure for UC that fails medical therapy or requires colectomy for dysplasia. See the dedicated procedure page for technique, complications, and functional outcomes.
• Continent ileostomy — historically the option for young UC patients before IPAA existed; largely superseded by IPAA. Continence is maintained by an intussuscepted segment of ileum (rather than the anal sphincter) between the reservoir and the end ileostomy; prone to desussception (the intussuscepted segment reduces spontaneously), which renders the stoma incontinent and requires revisional surgery. Works best in thin patients — heavier mesentery in larger patients predisposes to desussception.

Open items / gaps

• No primary trial data yet on IPAA vs. ileorectal anastomosis vs. end ileostomy outcomes, or on chromoendoscopy vs. random biopsy surveillance effectiveness — the ACG 2025 guideline explicitly excludes surveillance/dysplasia management from its scope, so this remains textbook-only.
• Pouchitis — mentioned only via the sclerosing-cholangitis risk link on Inflammatory Bowel Disease; no dedicated coverage yet.
• Cuffitis (retained-rectal-mucosa inflammation after IPAA) mentioned only briefly on Ileal Pouch-Anal Anastomosis (IPAA) — not developed as its own topic.
• The ACG and AGA guidelines take explicitly different methodological stances on ranking therapies by network meta-analysis (see “Efficacy positioning” subsection above) — treat their positioning tables as reflecting different evidentiary philosophies, not reconcilable into one ranking, except where real head-to-head RCT data exists (vedolizumab vs. adalimumab).
• ASUC section (from ACG 2025 only, not covered by AGA 2024’s narrower moderate-severe-outpatient scope) still rests on a single guideline for its day-by-day algorithm, though BSG 2025 - IBD Guidelines (Adults) (ingested alongside ACG/AGA) covers UC broadly too and wasn’t exhaustively cross-checked against this page’s specific numbers — see that guideline’s own Limitations note. BSG’s therapeutic-drug-monitoring and pregnancy content (both cross-cutting UC+Crohn’s topics) was filed on Inflammatory Bowel Disease instead of duplicated here.