What is the treatment for ulcerative colitis (UC)?

Treatment of Ulcerative Colitis

For mild-to-moderate UC, start with combination topical mesalazine 1g daily plus oral mesalamine 2-4g daily, as this is superior to monotherapy; for moderate-to-severe UC, use advanced therapies (infliximab, vedolizumab, ustekinumab, tofacitinib, upadacitinib) over corticosteroids for long-term management. 1, 2

Disease Severity Classification

Before initiating treatment, classify disease severity using validated criteria 3:

• Mild-to-moderate disease: Manageable as outpatient with bloody stools <6/day 3
• Severe disease: Requires hospitalization with bloody stool frequency ≥6/day PLUS tachycardia >90/min, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h 3
• Moderate-to-severe UC: Defined as Mayo endoscopy sub-score 2-3, or mild symptoms with high inflammatory burden, or corticosteroid-dependent disease 1

Treatment Algorithm by Disease Extent and Severity

Mild-to-Moderate Distal UC (Proctitis and Left-Sided Disease)

First-line therapy: Combination topical mesalazine 1g daily (suppositories for proctitis, enemas for left-sided disease) PLUS oral mesalamine 2-4g daily 2, 3

• Topical mesalazine is more effective than topical corticosteroids 3
• Once-daily dosing is preferred over multiple daily doses 1
• Combination therapy achieves superior remission rates compared to either agent alone 2, 3

Second-line therapy: Topical corticosteroids for patients intolerant to topical mesalazine 2

Mild-to-Moderate Extensive UC

First-line therapy: Oral 5-ASA at least 2g/day (optimal dose 2-4g daily) 1, 2

• Do NOT switch between different oral 5-ASA formulations if initial therapy fails, as this is ineffective 1
• Oral budesonide MMX can be considered as an alternative first-line option 1

Second-line therapy: Oral corticosteroids to induce remission 1

• Evaluate for symptomatic response within 2 weeks 1, 2
• Taper gradually over 8 weeks to prevent early relapse 3

Moderate-to-Severe UC

The AGA strongly recommends the following advanced therapies over no treatment 1:

Preferred agents (strong recommendation, moderate-to-high certainty):

• Infliximab 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 1, 4
• Vedolizumab 1
• Ustekinumab 1
• Tofacitinib 1
• Upadacitinib 1
• Ozanimod 1
• Etrasimod 1
• Risankizumab 1
• Guselkumab 1

Alternative agents (conditional recommendation):

• Adalimumab 1
• Filgotinib 1
• Mirikizumab 1

Critical Implementation Considerations

JAK inhibitor restrictions: In the United States, FDA labels recommend JAK inhibitors (tofacitinib, filgotinib, upadacitinib) only after prior failure or intolerance to TNF antagonists 1

Combination therapy with immunomodulators: Combine TNF antagonists with thiopurines or methotrexate rather than using TNF antagonist monotherapy, as combination therapy is superior for inducing remission 1

Biosimilars: Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs 1

Extended induction: For severe disease, consider extended induction regimens up to 16 weeks or dose escalation 1

Severe Acute UC with Toxic Colitis (Hospitalized Patients)

First-line: IV corticosteroids - hydrocortisone 100mg four times daily OR methylprednisolone 30mg every 12 hours (preferred due to less mineralocorticoid effect) 2

Supportive care:

• IV fluid and electrolyte replacement with potassium supplementation ≥60 mmol/day 2
• Low-molecular-weight heparin for thromboprophylaxis (rectal bleeding is NOT a contraindication) 2
• Daily monitoring of stool frequency, vital signs, CBC, CRP, albumin, electrolytes 2

Response assessment: Evaluate after 3-5 days of IV corticosteroids 2

Rescue therapy (if inadequate response by day 3-5): Infliximab 5mg/kg OR ciclosporin 2mg/kg/day 2

Maximum IV steroid duration: 7-10 days maximum, as prolonged courses increase toxicity without additional benefit 2

Surgical consultation: Required if symptoms persist despite optimized medical therapy, as approximately 20-29% of acute severe UC patients require colectomy during admission 2

Maintenance Therapy

Lifelong maintenance is mandatory to reduce relapse risk and potentially reduce colorectal cancer risk 3:

For 5-ASA-induced remission: Continue oral 5-ASA at least 2g/day 1

For corticosteroid-induced remission: Thiopurine monotherapy (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) can be considered, though this is second-line due to toxicity 1, 2

For anti-TNF responders: Continue anti-TNF therapy indefinitely 1

For patients on combination therapy (TNF antagonist + immunomodulator) in corticosteroid-free remission for ≥6 months: Do NOT withdraw TNF antagonist 1

What NOT to Do: Critical Pitfalls

Never use corticosteroids for maintenance therapy - they are ineffective and associated with significant adverse effects 1

Never use thiopurine monotherapy to induce remission - it is ineffective for induction 1

Never use methotrexate monotherapy - it is ineffective for both induction and maintenance 1

Never use monotherapy when combination therapy is indicated - topical plus oral 5-ASA is superior to either alone for distal disease 3

Never continue 5-ASA after escalating to advanced therapies - discontinue 5-ASA in patients who have escalated to immunomodulators or biologics after failing 5-ASA 1

Avoid anti-diarrheal medications in severe disease - they can precipitate toxic megacolon 2

Monitoring and Follow-up

Evaluation timeframes 1, 2:

• Corticosteroid therapy: Assess response within 2 weeks
• Anti-TNF therapy: Assess response at 8-12 weeks
• Patients not responding by week 14 of biologics are unlikely to respond with continued dosing and should be switched 4

Therapeutic drug monitoring: Check drug levels and antibodies to optimize adalimumab or infliximab therapy in patients with suboptimal response 2

Colonoscopy surveillance: Initial screening at 8 years from diagnosis for dysplasia surveillance 5