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 Based on Disease Location

Ulcerative Proctitis (Limited to Rectum)

1. 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 1
   • Topical mesalamine is more effective than topical corticosteroids 1

2. If inadequate response or intolerance:

   • Add oral mesalamine ≥2.4g/day or
   • Add/substitute topical corticosteroids 1

3. For refractory proctitis:

   • Oral corticosteroids
   • Consider topical tacrolimus, JAK inhibitors, S1P agonists, or biologic therapy 1

Left-sided Colitis (Extending up to Splenic Flexure)

1. First-line: Combination therapy with:

   • Oral mesalamine ≥2.4g/day AND
   • Mesalamine enema ≥1g/day 1

2. If inadequate response within 2-4 weeks:

   • Add oral corticosteroids (prednisolone 40mg/day) 1

Extensive Colitis (Beyond Splenic Flexure)

1. First-line: Combination therapy with:

   • Oral mesalamine ≥2.4g/day AND
   • Mesalamine enema 1g/day 1

2. If inadequate response within 2 weeks:

   • Add oral corticosteroids (prednisolone 40mg/day) 1

Treatment Based on Disease Severity

Mild to Moderate Disease

1. First-line: 5-ASA compounds

   • Oral mesalamine starting at 2.4-4.8g/day (higher initial dose is more effective) 1, 2
   • Once-daily dosing is as effective as divided doses and improves compliance 1

2. If inadequate response after 2-4 weeks:

   • Add oral corticosteroids (prednisolone) 1
   • Consider budesonide MMX for left-sided disease refractory to 5-ASA 1

Moderate to Severe Disease

1. First-line:

   • Oral prednisolone 40mg/day combined with 5-ASA 1
   • High-dose 5-ASA alone can be considered initially, but corticosteroids should be started if no response within 2 weeks 1

2. If inadequate response to oral corticosteroids within 2 weeks:

   • Initiate advanced therapy (biologics or small molecules) 1, 3

Severe Disease/Hospitalization

1. Immediate management:

   • Hospital admission for intensive treatment 1
   • IV corticosteroids (methylprednisolone 60mg/day or hydrocortisone 100mg four times daily) 4
   • Joint management by gastroenterologist and colorectal surgeon 4

2. If no response to intensive therapy:

   • Consider infliximab rescue therapy 3
   • Consider surgical consultation for colectomy 1

Maintenance Therapy

1. After 5-ASA-induced remission:

   • Continue 5-ASA at ≥2g/day for maintenance 1, 4
   • Lifelong therapy recommended, especially for left-sided or extensive disease 1, 4

2. After corticosteroid-induced remission:

   • Corticosteroids are not recommended for maintenance 1
   • Continue 5-ASA or consider immunomodulators (azathioprine, 6-mercaptopurine) 1, 4

3. After biologic-induced remission:

   • Continue the agent successful in achieving induction 1
   • For infliximab, consider combination with azathioprine 4, 3

Advanced Therapies for Refractory Disease

1. Biologic agents:

   • Anti-TNF agents (infliximab): 5mg/kg at weeks 0,2, and 6, then every 8 weeks 3
   • Anti-integrin agents (vedolizumab) 4
   • Anti-IL12/23 agents (ustekinumab) 5

2. Small molecules:

   • JAK inhibitors (tofacitinib) 5
   • S1P modulators (ozanimod) 5

Important Considerations

• Dosing: Higher doses of 5-ASA (≥2.4g/day) are more effective, particularly in extensive disease 1
• Compliance: Once-daily dosing improves adherence 1
• Cancer prevention: Long-term 5-ASA therapy may reduce colorectal cancer risk 1, 4
• Monitoring: Regular assessment of symptoms, inflammatory markers, and periodic endoscopic evaluation 5
• C. difficile testing: Always test for C. difficile infection before starting immunosuppressive therapy 4

Common Pitfalls to Avoid

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

By following this structured approach based on disease location and severity, most patients with ulcerative colitis can achieve and maintain remission, improving their quality of life and reducing long-term complications.