What is the treatment for ulcerative colitis?

Treatment of Ulcerative Colitis: A Stepwise Approach

The treatment of ulcerative colitis should follow a stepwise approach starting with 5-aminosalicylates for mild to moderate disease, progressing to corticosteroids for non-responders, and advancing to biologics or small molecules for refractory cases, with the goal of achieving complete clinical, biochemical, and endoscopic remission. 1, 2

Disease Classification and Initial Treatment

Mild to Moderate Ulcerative Colitis

• For ulcerative proctitis (limited to rectum):

  • First-line: Topical 5-ASA therapy (1g daily) 1, 2
  • If inadequate response: Add oral 5-ASA (2-4g daily) or switch to topical corticosteroids 1

• For left-sided or extensive UC:

  • First-line: Oral 5-ASA (2-4g daily) or balsalazide (6.75g daily) 2
  • Combine with topical 5-ASA for enhanced efficacy 1, 2
  • Assess response within 2-4 weeks 1

Moderate to Severe Ulcerative Colitis

• Initial therapy:
  • Oral prednisolone 40mg daily combined with 5-ASA 1
  • High-dose 5-ASA alone can be tried but initiate corticosteroids if no response within 2 weeks 1

Treatment Escalation for Inadequate Response

Non-response to First-line Therapy

• If no response to oral 5-ASA within 2-4 weeks, add oral prednisolone 40mg daily 1, 2
• Taper prednisolone over 8 weeks once response is achieved 1

Corticosteroid-Dependent or Resistant Disease

• Advanced therapy options:

  • TNF antagonists (infliximab, adalimumab, golimumab) 1
  • Integrin inhibitors (vedolizumab) 1
  • IL-12/23 inhibitors (ustekinumab) 1
  • JAK inhibitors (tofacitinib, upadacitinib) 1
  • S1P receptor modulators (ozanimod, etrasimod) 1

• Important considerations:

  • TNF antagonists are more effective when combined with immunomodulators 1
  • JAK inhibitors have FDA restrictions recommending use after TNF antagonist failure 1

Maintenance Therapy

• For mild to moderate disease in remission:

  • Continue 5-ASA at ≥2g/day for lifelong maintenance 2

• For frequent relapsers (>1/year):

  • Consider thiopurines (azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day) 2
  • Note: Thiopurines are not recommended for induction of remission 1

• For moderate to severe disease:

  • Continue the agent that successfully induced remission 1
  • Important: Corticosteroids should never be used for long-term maintenance 1, 2
  • For patients on combination therapy (TNF antagonist plus immunomodulator), continue the TNF antagonist rather than withdrawing it 1

Management of Acute Severe Ulcerative Colitis

• Requires hospitalization with:
  • IV corticosteroids (methylprednisolone 60mg/day or hydrocortisone 100mg four times daily) 2
  • Assess response by day 3 of IV steroids 1
  • For non-responders, consider rescue therapy with:
    • Ciclosporin (2-4mg/kg/day) 1
    • Infliximab (5mg/kg at 0,2, and 6 weeks) 1, 3
    • Tacrolimus 1
  • Consider colectomy if no improvement after 4-7 days of salvage therapy 1

Supportive Care

• Venous thromboembolism prophylaxis with low-molecular-weight heparin 1, 2
• Nutritional support if malnourished (enteral preferred over parenteral) 1
• Avoid anticholinergics, anti-diarrheals, NSAIDs, and opioids during acute flares 1
• Blood transfusion to maintain hemoglobin above 8-10 g/dl if needed 1

Common Pitfalls and Caveats

1. Delayed escalation of therapy: Failing to escalate therapy promptly when patients don't respond to initial treatment can lead to worse outcomes and increased risk of colectomy.

2. Prolonged corticosteroid use: Corticosteroids should never be used for maintenance therapy due to significant side effects.

3. Inadequate dosing: Underdosing 5-ASA compounds is common; ensure adequate dosing (≥2g/day for maintenance).

4. Missing concomitant infections: Always consider testing for infections in acute flares, especially in patients on immunosuppressive therapy.

5. Treatment goals too limited: Aiming only for symptom control rather than complete remission (clinical, biochemical, and endoscopic) may lead to ongoing inflammation and disease progression.

By following this stepwise approach and avoiding common pitfalls, the management of ulcerative colitis can be optimized to improve patient outcomes, reduce morbidity and mortality, and enhance quality of life.