What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

The first-line treatment for ulcerative colitis is 5-aminosalicylic acid (5-ASA) compounds, with therapy selection based on disease location and severity, escalating to corticosteroids, immunomodulators, and biologics for refractory disease. 1

Treatment Algorithm Based on Disease Location and Severity

Proctitis (Rectal Involvement Only)

• First-line: Topical mesalamine (5-ASA) 1g suppository once daily 1
  • Suppositories are preferred over enemas for proctitis as they deliver medication more effectively to the rectum
  • Topical mesalamine is more effective than topical corticosteroids
• If inadequate response: Add oral mesalamine ≥2.4g/day

Left-Sided Colitis

• First-line: Combination therapy with oral mesalamine ≥2.4g/day and mesalamine enema ≥1g/day 1
• If inadequate response within 2-4 weeks: Add oral corticosteroids (prednisolone 40mg/day)

Extensive Colitis

• First-line: Combination therapy with oral mesalamine ≥2.4g/day and mesalamine enema 1g/day 1
• If inadequate response within 2 weeks: Add oral corticosteroids (prednisolone 40mg/day)

Acute Severe Ulcerative Colitis

• Requires hospitalization: IV corticosteroids (methylprednisolone 60mg/day or hydrocortisone 100mg four times daily) 1
• Joint management by gastroenterologist and colorectal surgeon is recommended

Treatment Escalation for Refractory Disease

Moderate to Severe Disease Not Responding to First-Line Therapy

• Biologic agents:
  • Anti-TNF agents (infliximab): 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 1, 2
  • Anti-integrin agents (vedolizumab) 1
• Small molecules:
  • JAK inhibitors (tofacitinib)
  • S1P modulators (ozanimod) 1

Maintenance Therapy

• After 5-ASA-induced remission: Continue 5-ASA at ≥2g/day 1

  • Lifelong therapy is recommended, especially for left-sided or extensive disease
  • Once-daily dosing improves adherence

• After corticosteroid-induced remission:

  • Corticosteroids are NOT recommended for maintenance
  • Continue 5-ASA or consider immunomodulators (azathioprine, 6-mercaptopurine) 1

Important Clinical Considerations

Dosing Principles

• Higher doses of 5-ASA (≥2.4g/day) are more effective, particularly in extensive disease 1, 3
• Treatment should start at optimal dosages (4.8g per day of the active 5-ASA moiety), rather than starting lower and increasing if treatment fails 3

Safety Considerations for Biologic Therapy

• Before starting biologics like infliximab:
  • Screen for latent tuberculosis and treat if positive 2
  • Test for opportunistic infections including C. difficile 1, 2
  • Consider risk of malignancy, particularly in younger patients on combination therapy with immunomodulators 2

Long-term Benefits

• Long-term 5-ASA therapy may reduce colorectal cancer risk 1
• Patients require monitoring of symptoms and biomarkers of inflammation (e.g., fecal calprotectin) 4
• Colonoscopy surveillance for dysplasia should begin 8 years after diagnosis 4, 5

Common Pitfalls to Avoid

• Underdosing 5-ASA: Starting with too low a dose (should start with at least 2.4g/day) 1, 3
• Delayed escalation: Waiting too long to escalate therapy when response is inadequate 1
• Prolonged steroid use: Continuing corticosteroids for maintenance (increased risk of side effects) 1, 5
• Overlooking topical therapy: Not utilizing combination of oral and topical therapy for distal disease 1, 6
• Missing infections: Failing to test for C. difficile or other infections before intensifying immunosuppression 1, 2

Despite advances in medical therapies, response rates to advanced treatments range from 30% to 60% in clinical trials. Approximately 20% of patients are hospitalized within 5 years of diagnosis, and about 7% require colectomy 4. Surgical treatment is reserved for patients who fail medical therapy or develop severe complications like hemorrhage, perforation, or cancer 5.