What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

Treatment for ulcerative colitis should be tailored based on disease extent, severity, and location, with 5-aminosalicylates (5-ASA) as first-line therapy for mild-to-moderate disease and escalation to corticosteroids, immunomodulators, or biologics for moderate-to-severe disease or those who fail initial therapy. 1

Treatment Based on Disease Extent and Severity

Mild-to-Moderate Ulcerative Colitis

Proctitis (Disease Limited to Rectum)

• Mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis 1, 2
• Suppositories deliver medication more effectively to the rectum and are better tolerated than enemas 2
• Topical mesalamine is more effective than topical corticosteroids and should be preferred 2, 3

Left-Sided Colitis

• Combination of aminosalicylate enema ≥1 g/day with oral mesalazine ≥2.4 g/day is recommended as first-line therapy 1, 2, 3
• This combination is more effective than either oral or topical aminosalicylates alone 2
• Once-daily dosing with mesalamine is as effective as divided doses and may improve adherence 2, 3

Extensive Colitis

• Oral mesalamine ≥2.4 g/day combined with topical mesalamine is recommended 3
• Standard dose mesalamine (2-3 grams/day) or diazo-bonded 5-ASA is recommended as first-line therapy 1
• Adding rectal mesalamine to oral 5-ASA therapy improves outcomes 1

Treatment Escalation for Suboptimal Response

• For suboptimal response to standard-dose mesalamine, increase to high-dose mesalamine (>3 grams/day) with rectal mesalamine 1
• If no improvement within 10-14 days or symptoms worsen, consider increasing oral mesalamine dose to 4.8 g/day 2
• Continue treatment for up to 40 days before determining failure 2
• If inadequate response to optimized mesalamine therapy, add oral corticosteroids such as prednisolone 40 mg daily with tapering over 6-8 weeks 1, 2
• Budesonide MMX 9 mg/day can be used as an alternative to conventional steroids in patients with mild to moderate UC who have inadequate response to 5-ASA 2

Moderate-to-Severe Ulcerative Colitis

• Oral corticosteroid therapy (prednisolone 40 mg daily) is appropriate for induction of remission 1, 3
• Prednisolone should be tapered gradually over approximately 8 weeks according to patient response 3
• After successful induction with corticosteroids, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 1
• For corticosteroid-resistant/dependent UC, anti-TNF therapy or vedolizumab is recommended 1
• Infliximab is FDA-approved for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy 4

Severe Ulcerative Colitis

• Severe UC requires hospital admission and joint management by gastroenterologist and colorectal surgeon 1, 3
• Patients should receive intravenous fluid and electrolyte replacement, and maintain hemoglobin >10 g/dl 1
• Subcutaneous heparin should be administered to reduce thromboembolism risk 1
• For patients with acute severe UC refractory to IV corticosteroids, infliximab or cyclosporine may be considered 1

Maintenance Therapy

• Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease 1, 2, 3
• 5-ASA compounds are effective and safe for maintenance therapy 3
• Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 1, 2
• Regular monitoring of renal function is recommended for patients on long-term 5-ASA therapy, including eGFR before starting, after 2-3 months, and then annually 2

Special Considerations

• Patients already on sulfasalazine in remission or with prominent arthritic symptoms may reasonably choose sulfasalazine 2-4g/day if alternatives are cost-prohibitive, despite higher intolerance rates 1
• Long-term steroid use should be avoided due to significant side effects 2
• Approximately 50% of patients experience short-term corticosteroid-related adverse events such as acne, edema, sleep and mood disturbance, glucose intolerance and dyspepsia 2
• Probiotics, curcumin, and fecal microbiota transplantation are not currently recommended for routine use in UC due to insufficient evidence 1
• Patients who required two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent or refractory, require treatment escalation with thiopurine, anti-TNF therapy, vedolizumab, or tofacitinib 2

Treatment Algorithm Summary

1. First-line therapy for mild-to-moderate UC: 5-ASA (oral and/or topical based on disease extent) 1, 2, 3, 5
2. If inadequate response: Increase 5-ASA dose and optimize combination of oral and topical therapy 1, 2
3. If still inadequate response: Add oral corticosteroids (prednisolone 40 mg daily with taper) 1, 2, 3
4. For corticosteroid-dependent/resistant disease: Escalate to immunomodulators (azathioprine/6-MP) or biologics (infliximab, vedolizumab, ustekinumab) 1, 2, 5
5. For severe disease: Hospitalization with IV corticosteroids; consider infliximab or cyclosporine for refractory cases 1, 3