What is the treatment for ulcerative colitis?

Treatment of Ulcerative Colitis

For ulcerative colitis treatment, 5-aminosalicylates (5-ASA) are the first-line therapy for mild to moderate disease, while moderate to severe disease requires advanced therapies including biologics (TNF antagonists, vedolizumab, ustekinumab), JAK inhibitors, or S1P modulators, with therapy selection based on disease severity and location. 1

Disease Classification and Initial Assessment

Disease Severity

• Mild to moderate UC: Mayo endoscopy sub-score 0-1
• Moderate to severe UC: Mayo endoscopy sub-score 2-3, high inflammatory burden, or poor prognostic features 2

Disease Location

• Proctitis: Limited to rectum
• Left-sided colitis: Extends up to splenic flexure
• Extensive colitis: Extends beyond splenic flexure

Treatment Algorithm

Mild to Moderate Disease

1. First-line therapy: 5-aminosalicylates (5-ASA)

   • Proctitis: Mesalamine suppositories 1g/day 1
   • Left-sided colitis: Oral mesalamine 2-4g/day combined with topical mesalamine enemas (≥1 g/day) 1
   • Extensive colitis: Oral mesalamine 2-3g/day (standard dose) or >3g/day (high dose) 1

   Higher maintenance doses (≥2 g/day) are associated with longer remission periods, especially in extensive disease 2

2. If no response within 2-4 weeks:

   • Oral prednisolone 40mg daily with 6-8 week taper 1

Moderate to Severe Disease

1. Initial therapy:

   • Oral prednisolone 40mg daily with gradual tapering over 6-8 weeks 1
   • For severe flares requiring hospitalization: IV methylprednisolone 60mg/day or hydrocortisone 100mg four times daily 1

2. If no response to corticosteroids within 2 weeks:

   • Initiate advanced therapy (biologics or small molecules) 1
   • Options include:
     • TNF antagonists (infliximab, adalimumab, golimumab)
     • Vedolizumab (anti-integrin)
     • Ustekinumab (anti-IL-12/23)
     • JAK inhibitors (tofacitinib, upadacitinib, filgotinib)
     • S1P modulators (ozanimod, etrasimod)
     • IL-23 inhibitors (risankizumab, guselkumab, mirikizumab) 2

3. For acute severe UC not responding to IV steroids:

   • Medical rescue therapy with infliximab in combination with a thiopurine 1
   • Consider colectomy if medical therapy fails

Maintenance Therapy

1. General principle: Continue with the agent that induced remission (except corticosteroids) 1

2. Mild to moderate disease:

   • 5-ASA ≥2 g/day lifelong 2, 1

3. Moderate to severe disease:

   • After corticosteroid-induced remission: Thiopurines (azathioprine or mercaptopurine) 1
   • After biologic-induced remission: Continue biologic therapy
   • For combination therapy: The AGA suggests against withdrawal of TNF antagonists in patients on combination therapy with immunomodulators who are in remission for at least 6 months 2

Special Considerations

Combination Therapy

• TNF antagonists combined with immunomodulators are more effective than either as monotherapy 2
• For patients on 5-ASA who escalate to immunomodulators or advanced therapies, consider stopping 5-ASA 2

JAK Inhibitor Restrictions

• FDA recommends JAK inhibitors (tofacitinib, filgotinib, upadacitinib) only after failure or intolerance to TNF antagonists 2
• Use cautiously in patients with cardiovascular risk factors, especially those ≥65 years, smokers, or those with history of cardiovascular disease 2

Monitoring

• Regular assessment of inflammatory markers (C-reactive protein, fecal calprotectin)
• Colonoscopy for dysplasia surveillance starting 8 years after diagnosis 3
• Monitor for complications including thromboembolism, which is more common during flares 1

Common Pitfalls to Avoid

1. Inadequate dosing of 5-ASA: Using less than 2g/day for maintenance therapy reduces effectiveness 2

2. Delayed escalation of therapy: Failure to escalate therapy within 2-4 weeks of non-response can lead to disease progression

3. Overlooking VTE prophylaxis: All hospitalized UC patients should receive thromboprophylaxis 1

4. Missing infectious causes: Always test for C. difficile and other pathogens before starting immunosuppressive therapy 1

5. Discontinuing effective maintenance therapy: Premature discontinuation increases risk of relapse

6. Overlooking cancer surveillance: Regular colonoscopy is needed due to increased colorectal cancer risk (4.5% after 20 years) 3

By following this evidence-based approach to UC treatment, clinicians can optimize outcomes, reduce complications, and improve quality of life for patients with this chronic inflammatory condition.