What is the treatment for ulcerative colitis?

Treatment for Ulcerative Colitis

The first-line treatment for ulcerative colitis is 5-aminosalicylic acid (5-ASA) compounds, with dosing dependent on disease location and severity, followed by corticosteroids for non-responders, and advanced therapies (biologics or small molecules) for refractory disease. 1, 2

Disease Classification and Initial Assessment

• Disease Location:

  • Proctitis: Disease limited to rectum
  • Distal colitis: Disease up to sigmoid-descending junction
  • Left-sided colitis: Disease up to splenic flexure
  • Extensive colitis: Disease extending proximal to splenic flexure

• Disease Severity:

  • Mild to moderate: <4-6 stools/day, minimal bleeding, no systemic symptoms
  • Moderate to severe: >6 stools/day, frequent bleeding, systemic symptoms

Treatment Algorithm by Disease Location and Severity

1. Distal Disease (Proctitis/Proctosigmoiditis)

• First-line: Combination of topical mesalazine 1g daily + oral mesalazine 2-4g daily 1, 2
• Second-line options if no response:
  • Add topical corticosteroids
  • Switch to oral prednisolone 40mg daily if combination therapy fails 1
  • Consider topical tacrolimus for refractory proctitis 1

2. Left-sided or Extensive Colitis

• Mild to moderate:

  • First-line: Oral mesalazine 2-4g daily or balsalazide 6.75g daily 1
  • Can combine with topical mesalazine for enhanced efficacy 1
  • If no response within 2-4 weeks, add oral prednisolone 40mg daily 1

• Moderate to severe:

  • First-line: Oral prednisolone 40mg daily + 5-ASA 1
  • Taper prednisolone gradually over 8 weeks 1
  • If no response within 2 weeks, initiate advanced therapy 1

3. Maintenance Therapy

• All patients should receive maintenance therapy 1, 2
• First-line maintenance: 5-ASA compounds at ≥2g/day for lifelong use 1
• For frequent relapsers: Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day 1, 2
• Continue with the agent successful in achieving induction (except corticosteroids) 1

Advanced Therapies for Refractory Disease

For patients who fail conventional therapy (5-ASA and corticosteroids):

1. Biologic agents:

   • Anti-TNF agents (e.g., infliximab 5mg/kg at 0,2,6 weeks, then every 8 weeks) 3
   • Anti-integrin agents (e.g., vedolizumab)
   • IL-12/23 inhibitors (e.g., ustekinumab)

2. Small molecules:

   • JAK inhibitors (e.g., tofacitinib)
   • S1P receptor modulators (e.g., ozanimod) 1, 2

Important Considerations and Caveats

• Treatment goals have shifted from clinical response to achieving biochemical, endoscopic, and histological remission 1, 4

• Corticosteroids should never be used for long-term maintenance due to side effects 1, 2

• Adherence to 5-ASA therapy is crucial - poor adherence is a major cause of treatment failure 5

• Higher doses of 5-ASA (≥2g/day) are more effective for maintenance, especially in extensive disease 1

• Combination therapy (oral + topical 5-ASA) is more effective than either alone 1

• Risk factors for 5-ASA failure include younger age, extensive colitis, early need for corticosteroids, and elevated inflammatory markers 5

• Treatment response monitoring should include symptoms assessment, biomarkers (e.g., fecal calprotectin), and periodic endoscopic evaluation 4

• Colorectal cancer surveillance should begin 8 years after diagnosis 4

• Despite advances in therapy, approximately 7% of patients require colectomy within 5 years of diagnosis 4