What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

The cornerstone of treatment for mild to moderate ulcerative colitis is 5-aminosalicylate (5-ASA) medications, with therapy tailored based on disease extent and severity. 1, 2

Treatment Based on Disease Location

Proctitis (Disease Limited to Rectum)

• First-line therapy: Mesalamine 1g suppository once daily 1
• Mesalamine foam or enemas are alternatives but suppositories deliver medication more effectively to the rectum and are better tolerated 1
• For patients intolerant or unresponsive to mesalamine suppositories, rectal corticosteroid therapy is recommended 1
• Refractory proctitis may require oral corticosteroids, immunosuppressants, or biologics 1

Left-sided Colitis (Disease Extends Proximal to Rectum but Not Past Splenic Flexure)

• First-line therapy: Combination of topical mesalamine (≥1g/day) plus oral mesalamine (≥2.4g/day) 1, 2
• This combination is more effective than either treatment alone 2, 3
• Once-daily dosing with mesalamine is as effective as divided doses and may improve adherence 1, 3
• Topical mesalamine is more effective than topical corticosteroids 1, 3
• For patients not responding to combination therapy within 2-4 weeks, oral prednisolone 40mg daily is recommended 1, 3

Extensive Colitis (Disease Extends Proximal to Splenic Flexure)

• First-line therapy: Oral mesalamine ≥2.4g/day combined with topical mesalamine enemas 1g/day 1, 2
• For moderate to severe disease or non-responders to mesalamine, systemic corticosteroids (prednisolone 40mg daily) are appropriate 1
• Severe extensive colitis requires hospital admission for intensive treatment 1

Medication Options

5-Aminosalicylates (5-ASA)

• Standard dose is 2-3 grams/day of mesalamine; high dose is >3 grams/day 1
• Available formulations include:
  • Mesalamine (delayed release, controlled release, MMX, enteric-coated granules) 1
  • Diazo-bonded 5-ASA (olsalazine, balsalazide) 1
  • Sulfasalazine (has higher incidence of side effects compared to newer 5-ASA drugs) 1, 2
• Topical formulations should be selected based on disease extent: suppositories for proctitis, foam or liquid enemas for more proximal disease 2, 4
• Rectal 5-ASA is superior to rectal corticosteroids for inducing symptomatic improvement and remission 4

Corticosteroids

• Indicated for moderate to severe UC or when 5-ASA therapy fails 1, 2
• Oral prednisolone 40mg daily is standard dosing 1, 2
• Budesonide MMX 9mg/day may be an alternative to conventional steroids in patients with left-sided disease who have inadequate response to 5-ASA 1
• Long-term steroid use should be avoided; corticosteroids are not recommended for maintenance therapy 1, 3

Advanced Therapies (for Moderate to Severe Disease)

• Indicated when there is no adequate response to oral corticosteroids within 2 weeks, if corticosteroid taper is unsuccessful, or to avoid repeated courses of corticosteroids 1
• Options include:
  • Biologics: Anti-TNF agents (e.g., infliximab), anti-integrins, anti-IL12/23 1, 5, 6
  • Small molecules: JAK inhibitors, S1P agonists 1, 6
  • Immunomodulators: Azathioprine (1.5-2.5mg/kg/day) or mercaptopurine (0.75-1.5mg/kg/day) for steroid-dependent disease 2

Maintenance Therapy

• Maintenance therapy should be continued with the agent successful in achieving induction 1
• 5-ASA compounds are effective and safe for maintenance therapy 2
• Corticosteroids are not recommended for long-term maintenance 1
• Lifelong maintenance therapy is generally recommended, especially for left-sided or extensive disease 2

Special Considerations

• The treatment goal has shifted from achieving clinical response to achieving remission, which should be assessed biochemically, endoscopically, and histologically 1
• Patients with high-risk features (age <40 years at diagnosis, extensive disease, severe endoscopic activity, extra-intestinal manifestations, elevated inflammatory markers) may benefit from more aggressive initial therapy 1
• Combination of oral and topical 5-ASA is more effective than either alone 2, 3
• Extended mesalamine treatment (up to 34 weeks) may be beneficial in inducing complete remission in patients unresponsive to conventional therapy 7
• High-dose 5-ASA therapy may be a valuable option for patients with moderately active disease without poor prognostic factors 8

Common Pitfalls and Caveats

• Always exclude infectious causes before attributing symptoms to IBD flare 3
• 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
• Patients with severe UC should be managed jointly by a gastroenterologist and colorectal surgeon 1, 3
• Despite advances in medical therapies, approximately 7% of patients with UC undergo colectomy within 5 years of diagnosis 6