What are the treatment options for ulcerative colitis?

Treatment of Ulcerative Colitis

Treatment for ulcerative colitis should be tailored based on disease location and severity, starting with 5-aminosalicylates (5-ASA) for mild-to-moderate disease and escalating to corticosteroids, immunomodulators, or biologics for moderate-to-severe disease or treatment failure. 1, 2

Treatment Algorithm by Disease Location and Severity

Ulcerative Proctitis (Disease Limited to Rectum)

First-line therapy is mesalamine 1-g suppository once daily, which delivers medication directly to the rectum and is better tolerated than other formulations 2, 3. Suppositories are superior to enemas or foam for proctitis because they reach the target area more effectively 3.

• Topical mesalamine is more effective than topical corticosteroids and should be preferred as initial therapy 2, 3
• If inadequate response, combine topical mesalamine with oral mesalamine ≥2.4 g/day, which is more effective than either agent alone 2, 3
• For refractory proctitis despite combination therapy, add oral corticosteroids (prednisolone 40 mg daily) or consider advanced therapies including JAK inhibitors, S1P agonists, or biologics 1

Left-Sided Colitis (Disease to Splenic Flexure)

Initial treatment should be aminosalicylate enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day, which is more effective than oral or topical therapy alone 2, 3.

• Once-daily dosing of oral mesalamine is as effective as divided doses and improves adherence 3
• If no improvement within 10-14 days or symptoms worsen, increase oral mesalamine to 4.8 g/day 3
• Continue optimized mesalamine therapy for up to 40 days before declaring treatment failure, as sustained remission may take time 3
• If inadequate response after 40 days, add oral prednisolone 40 mg daily with tapering over 6-8 weeks 1, 3
• Alternative: budesonide MMX 9 mg/day for left-sided disease has fewer systemic side effects than conventional steroids 3

Extensive Colitis (Disease Beyond Splenic Flexure)

Start with oral mesalamine 2-4 g/day or balsalazide 6.75 g/day as first-line therapy for mild to moderately active disease 1.

• Adding rectal mesalamine to oral therapy provides superior outcomes 2, 4
• For suboptimal response to standard-dose mesalamine, escalate to high-dose mesalamine (>3 g/day, up to 4.8 g/day) with rectal mesalamine 2, 3
• The median time to cessation of rectal bleeding is approximately 9 days with high-dose mesalamine (4.8 g/day) compared to 16 days with standard dose (2.4 g/day) 3

Moderate-to-Severe Disease

Oral prednisolone 40 mg daily is appropriate for patients requiring prompt response or those who failed optimized mesalamine therapy 1, 2.

• Prednisolone should be reduced gradually over 8 weeks according to severity and patient response 1
• More rapid reduction is associated with early relapse 1
• Single daily dosing of prednisolone is as effective as split-dosing and causes less adrenal suppression 4
• After successful induction with corticosteroids, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 2, 4

Corticosteroid-Dependent or Refractory Disease

Long-term steroid use should be avoided—patients requiring two or more courses of corticosteroids in the past year or who become steroid-dependent require treatment escalation 1, 4.

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day for chronic active steroid-dependent disease 1
• For corticosteroid-resistant/dependent UC, anti-TNF therapy or vedolizumab is recommended 2
• Infliximab and vedolizumab are preferred first-line biologics in biologic-naïve patients 4
• Combination therapy (biologic + immunomodulator) is more effective than monotherapy 4

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Severe UC should be managed jointly by a gastroenterologist and colorectal surgeon with daily physical examination to evaluate for abdominal tenderness and rebound 2, 4.

• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) is the mainstay of treatment 1, 4
• Provide IV fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, and administer subcutaneous heparin to reduce thromboembolism risk 2, 4
• For patients refractory to IV corticosteroids, infliximab or cyclosporine may be considered 2, 4
• Infliximab (RENFLEXIS) is FDA-approved at 5 mg/kg given as an intravenous induction regimen at 0,2, and 6 weeks followed by maintenance of 5 mg/kg every 8 weeks 5

Maintenance Therapy

Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease, to reduce relapse risk and potentially the risk of colorectal cancer 2, 4.

• Continue maintenance therapy with the agent successful in achieving induction, with the critical exception that corticosteroids are not recommended for long-term maintenance 1
• Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 2, 4
• 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 3, 4

Important Clinical Considerations

Monitor patients for response to therapy—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.

• Patients who do not respond by Week 14 of biologic therapy are unlikely to respond with continued dosing and consideration should be given to discontinue 5
• Approximately 50% of patients experience short-term corticosteroid-related adverse events such as acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia 4
• The overall treatment goal has shifted from achieving clinical response to achieving remission, which should be assessed biochemically or endoscopically and histologically 1