What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

The first-line treatment for mild to moderate ulcerative colitis is aminosalicylates (5-ASA), with therapy tailored based on disease extent and severity, while more severe disease requires systemic corticosteroids, and refractory cases may need advanced therapies including biologics or small molecules.

Treatment Based on Disease Location and Severity

Ulcerative Proctitis (Limited to Rectum)

• First-line therapy: Mesalamine 1g suppository once daily 1, 2
• Mesalamine foam or enemas are alternatives but suppositories deliver medication more effectively to the rectum and are better tolerated 1
• Topical mesalamine is more effective than topical corticosteroids 1, 2
• For patients who don't respond to topical mesalamine:
  • Add oral mesalamine ≥2.4g/day 1, 2
  • Consider rectal corticosteroids if intolerant to mesalamine suppositories 1
• Refractory proctitis may require systemic corticosteroids, immunosuppressants, or biologics 1

Left-Sided Colitis (Extending Proximal to Rectum but Not Past Splenic Flexure)

• First-line therapy: Combination of oral mesalamine ≥2.4g/day plus mesalamine enema ≥1g/day 1, 2
• This combination is more effective than either oral or topical therapy alone 1, 2
• Once-daily dosing with mesalamine is as effective as divided doses 1, 2
• If no response within 2-4 weeks, add oral corticosteroids (prednisolone 40mg/day) 1
• For patients who prefer rectal therapy, mesalamine enemas are more effective than rectal corticosteroids 1

Extensive Colitis (Extending Proximal to Splenic Flexure)

• First-line therapy: Oral mesalamine ≥2.4g/day combined with mesalamine enema 1g/day 1, 2
• For moderate to severe disease or those not responding to mesalamine, systemic corticosteroids (prednisolone 40mg/day) are appropriate 1
• Severe extensive colitis requires hospital admission for intensive treatment 1, 2

Medication Options

Aminosalicylates (5-ASA)

• Standard dose: 2-3g/day of mesalamine 1
• High dose: >3g/day of mesalamine (may be more effective for moderate disease) 1, 2
• Options include:
  • Mesalamine (various formulations) 1, 2
  • Diazo-bonded 5-ASA (balsalazide, olsalazine) 1, 2
  • Sulfasalazine (higher incidence of side effects) 1, 2
• Efficacy and safety are similar among different 5-ASA formulations at equivalent doses 1
• Rectal 5-ASA is superior to rectal corticosteroids for inducing symptomatic improvement and remission 3

Corticosteroids

• Indicated for moderate to severe UC or when 5-ASA therapy fails 1
• Standard dosing: Prednisolone 40mg/day 1
• Should be tapered gradually over approximately 8 weeks 1
• Not recommended for long-term maintenance due to side effects 1
• Budesonide MMX can be considered for mild-moderate UC refractory to optimized oral and rectal 5-ASA 1

Advanced Therapies (for Refractory Disease)

• Biologics such as infliximab (5mg/kg at weeks 0,2, and 6, then every 8 weeks) for moderate to severe UC 4
• Immunomodulators (azathioprine, mercaptopurine) for steroid-dependent disease 1
• Newer options include JAK inhibitors and S1P agonists 1

Maintenance Therapy

• Lifelong maintenance therapy is generally recommended, especially for left-sided or extensive disease 1
• Continue with the agent successful in achieving induction, except corticosteroids 1
• 5-ASA compounds are effective and safe for maintenance therapy 1, 5
• Once-daily dosing with mesalamine is as effective as divided doses for maintenance 1

Treatment Goals and Monitoring

• The treatment goal has shifted from achieving clinical response to achieving complete remission 1
• Remission should be assessed biochemically, endoscopically, and histologically 1, 5
• Monitor renal function periodically in patients on 5-ASA therapy 1

Common Pitfalls and Caveats

• Avoid repeated courses of corticosteroids, even in those with mild-moderate disease 1
• Consider escalation of therapy in patients who frequently need corticosteroids for disease control 1
• Recognize that certain disease features may predict an aggressive course, including age <40 years at diagnosis, extensive disease, severe endoscopic activity, extraintestinal manifestations, and elevated inflammatory markers 1
• The benefit of 5-ASA is well-documented for ulcerative colitis but has limited efficacy in Crohn's disease 6
• Despite advances in medical therapies, approximately 7% of patients with UC undergo colectomy within 5 years of diagnosis 5