What is the treatment for ulcerative colitis?

Treatment of Ulcerative Colitis

For mild-to-moderate ulcerative colitis, start with oral mesalamine 2.4-4.8 g/day combined with topical mesalamine therapy, escalating to oral prednisolone 40 mg daily if no response within 2-4 weeks; for moderate-to-severe disease, use prednisolone 40 mg daily or advance directly to biologic therapy (infliximab or vedolizumab preferred), and maintain lifelong therapy with the agent that achieved remission, never using corticosteroids for maintenance. 1, 2, 3

Treatment Algorithm by Disease Location and Severity

Ulcerative Proctitis (Disease Limited to Rectum)

• First-line: Mesalamine 1 g suppository once daily—suppositories deliver medication more effectively to the rectum than foam or enemas and are better tolerated 2, 4
• Enhanced efficacy: Combine topical mesalamine with oral mesalamine ≥2.4 g/day, which is more effective than either alone 2, 4
• If topical mesalamine fails or is not tolerated: Add or substitute oral 5-ASA or topical corticosteroids (though topical mesalamine is superior to topical steroids) 1, 2
• Refractory proctitis: Escalate to oral corticosteroids, topical tacrolimus, JAK inhibitors, S1P agonists, or biologic therapy 1

Left-Sided Colitis (Disease to Splenic Flexure)

• First-line: Mesalamine enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day—this combination is more effective than oral or topical therapy alone, and superior to topical steroids 1, 2, 4
• Dosing advantage: Once-daily dosing is as effective as divided doses and improves adherence 2, 3
• If inadequate response: Oral prednisolone 40 mg daily for patients who fail combination 5-ASA therapy 1, 2
• Alternative before steroids: Budesonide MMX 9 mg/day can be used for left-sided disease inadequately controlled with oral 5-ASA 4

Extensive Colitis (Disease Beyond Splenic Flexure)

• Mild-to-moderate disease: Oral mesalamine 2.4-4.8 g/day combined with mesalamine enema 1 g/day 1, 2, 4
• Higher doses for suboptimal response: High-dose mesalamine >3 g/day (up to 4.8 g/day) with rectal mesalamine for moderate disease activity 2, 5
• Moderate-to-severe disease: Oral prednisolone 40 mg daily is appropriate when prompt response is required or when mesalamine fails 1, 2
• Severe extensive colitis: Requires hospital admission for intensive intravenous treatment 4

Corticosteroid Management

Induction Therapy

• Standard dose: Prednisolone 40 mg daily for moderate-to-severe ulcerative colitis 1, 2
• Evidence basis: 40 mg/day prednisolone is more effective than 20 mg/day, with no additional benefit from doses higher than 40-60 mg/day but increased adverse effects 1
• Taper schedule: Reduce gradually over 8 weeks according to severity and patient response—more rapid reduction is associated with early relapse 1, 4

Critical Limitation

• Never use for maintenance: Corticosteroids are not recommended for long-term maintenance therapy 1, 2
• Steroid-dependent disease: Patients with chronic active steroid-dependent disease should be treated with azathioprine 1.5-2.5 mg/kg/day, mercaptopurine 0.75-1.5 mg/kg/day, or advanced to biologic therapy 1

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Immediate Management

• Joint care: Management should be joint between gastroenterologist and colorectal surgeon, with daily physical examination for abdominal tenderness and rebound 2, 3
• Intravenous steroids: Hydrocortisone 400 mg/day or methylprednisolone 60 mg/day as mainstay of treatment 2, 3
• Supportive care: Provide IV fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, and administer subcutaneous heparin to reduce thromboembolism risk 2, 3

Steroid-Refractory Disease

• Rescue therapy: For patients refractory to IV corticosteroids within 3-5 days, infliximab or cyclosporine may be considered 2, 3
• Infliximab dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 6

Advanced Therapy (Biologics and Small Molecules)

Indications for Escalation

• Timing: Start advanced therapy if no adequate response to oral corticosteroids within 2 weeks, if corticosteroid taper is unsuccessful, or to avoid repeated courses of corticosteroids 1
• Preferred first-line biologics: Infliximab and vedolizumab are recommended as preferred first-line biologics in biologic-naïve patients 3

Combination Therapy

• Enhanced efficacy: Combination therapy (biologic + immunomodulator) is more effective than monotherapy 3
• Specific recommendation: Purine analogues (azathioprine/mercaptopurine) are suggested alongside infliximab therapy 1

FDA-Approved Indication

• Infliximab (Renflexis): Indicated 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 6

Maintenance Therapy

Lifelong Treatment Recommendation

• General principle: Lifelong maintenance therapy is recommended for all patients, especially those with left-sided or extensive disease 1, 2, 3
• Dosing for maintenance: 5-ASA doses of ≥2 g/day are recommended—time spent in remission is longer when maintenance dose is increased from 1.2 to 2.4 g/day, with extensive disease benefiting most 1
• Continuing induction dose: When 5-ASA is used to induce remission, continuing the induction dosage for an extra 4 weeks prolongs remission and reduces relapse frequency 1

Discontinuation Considerations

• When to stop 5-ASA: Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 2, 3
• Distal disease exception: It may be reasonable to discontinue medication for patients with distal disease who have been in remission for at least 2 years, though continued therapy reduces colorectal cancer risk 1

Treatment Goals and Monitoring

Therapeutic Targets

• Shift in goals: Overall treatment goal has shifted from achieving clinical response to achieving remission, assessed biochemically or endoscopically and histologically 1
• Mucosal healing: Histologic remission is achieved after induction in up to 45% of patients with topical 5-ASA and 30% with oral formulations 7

Response Assessment

• Timeline for 5-ASA: Monitor for response; if symptoms deteriorate, rectal bleeding persists beyond 10-14 days, or sustained relief has not been achieved after 40 days of appropriate 5-ASA therapy, escalate treatment 2
• Timeline for corticosteroids: Patients who do not respond by week 14 are unlikely to respond with continued dosing and should be considered for treatment discontinuation or escalation 6

Common Pitfalls and Caveats

Dosing Errors

• Avoid underdosing: Start with standard-dose mesalamine 2.4-4.8 g/day rather than starting low and escalating—patients rarely comply fully with prescribed dose regimens, leading to effective underdosing 1, 2
• Don't forget topical therapy: Combination topical plus oral mesalamine is significantly more effective than oral alone in ulcerative colitis—this is a frequently overlooked strategy 2, 4

Medication Selection

• Sulfasalazine limitations: Has higher incidence of side effects compared with newer 5-ASA drugs; reserve for selected patients such as those with reactive arthropathy or when alternatives are cost-prohibitive 1, 2
• Olsalazine caution: Has higher incidence of diarrhea in pancolitis; best for patients with left-sided disease or intolerance of other 5-ASA 1

Safety Considerations

• Biologic risks: Infliximab carries boxed warnings for serious infections (including tuberculosis, invasive fungal infections, bacterial/viral/opportunistic infections) and malignancy risk, particularly hepatosplenic T-cell lymphoma in young males receiving concomitant azathioprine or mercaptopurine 6
• TB screening: Treatment for latent tuberculosis infection should be initiated prior to infliximab use 6

Therapies Not Recommended

• Insufficient evidence: Probiotics, curcumin, and fecal microbiota transplantation are not currently recommended for routine use in ulcerative colitis due to insufficient evidence 2