What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

Treatment Algorithm Based on Disease Severity and Location

Treatment for ulcerative colitis should be stratified by disease extent (proctitis, left-sided, or extensive disease) and severity (mild-to-moderate, moderate-to-severe, or acute severe), with 5-aminosalicylates as first-line therapy for mild-to-moderate disease and escalation to corticosteroids, biologics, or immunomodulators for more severe or refractory cases. 1, 2

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Mild-to-Moderate Disease

Proctitis (Disease Limited to Rectum)

• Mesalamine 1-gram suppository once daily is the preferred initial treatment, as suppositories deliver medication more effectively to the rectum and are better tolerated than foam or enemas 1, 3
• Topical mesalamine is more effective than topical corticosteroids and should be preferred as first-line therapy 1, 3
• Combining topical mesalamine with oral mesalamine (≥2.4 g/day) is more effective than either agent alone for controlling inflammation and symptoms 1, 3

Left-Sided Colitis (Disease to Splenic Flexure)

• Start with aminosalicylate enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day, which is more effective than oral or topical therapy alone 1, 3
• Once-daily dosing of oral mesalamine is as effective as divided doses and improves adherence 1, 3
• If no improvement within 10-14 days or symptoms worsen, increase oral mesalamine to 4.8 g/day 3

Extensive Colitis (Disease Beyond Splenic Flexure)

• Standard-dose mesalamine 2-3 g/day combined with rectal mesalamine is recommended as first-line therapy 1, 2
• For suboptimal response to standard dosing, escalate to high-dose mesalamine (>3 g/day or 4.8 g/day) with rectal mesalamine 1, 3
• Continue optimized mesalamine therapy for up to 40 days before determining treatment failure, as sustained remission may take time 3

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Moderate-to-Severe Disease

Corticosteroid Induction

• Oral prednisolone 40 mg daily is appropriate for induction of remission in patients who fail optimized mesalamine therapy or require prompt response 4, 1, 2
• Taper prednisolone gradually over 6-8 weeks according to severity and patient response; more rapid reduction is associated with early relapse 4, 1, 3
• Single daily dosing of prednisolone is as effective as split-dosing and causes less adrenal suppression 3
• Budesonide MMX 9 mg/day can be used as an alternative to conventional steroids for left-sided disease, with fewer systemic side effects 3

Transition to Maintenance Therapy

• After successful corticosteroid induction, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 1, 2
• Long-term corticosteroid use should be avoided due to significant side effects 4, 3

Biologic Therapy

• For corticosteroid-resistant or corticosteroid-dependent disease, anti-TNF therapy (infliximab) or vedolizumab is recommended 1, 2
• Infliximab and vedolizumab are preferred first-line biologics in biologic-naïve patients with moderate-to-severe disease 2
• Infliximab dosing is 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 5
• Combination therapy (biologic plus immunomodulator) is more effective than monotherapy, though this must be weighed against the risk of hepatosplenic T-cell lymphoma, particularly in young males 2, 5

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Acute Severe Ulcerative Colitis (Hospitalized Patients)

Initial Management

• Severe UC should be managed jointly by a gastroenterologist and colorectal surgeon, with daily physical examination to evaluate for abdominal tenderness and rebound 1, 2
• Provide IV fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, and administer subcutaneous heparin to reduce thromboembolism risk 1, 2
• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) is the mainstay of treatment 1, 2

Rescue Therapy for Steroid-Refractory Disease

• For patients with acute severe UC refractory to IV corticosteroids, infliximab or cyclosporine may be considered 1
• Both agents have similar efficacy; choice depends on local expertise and patient factors 1

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Maintenance Therapy

Long-Term Management

• Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease, to reduce relapse risk and potentially reduce colorectal cancer risk 1, 2, 3
• Patients in remission on biologics and/or immunomodulators after prior 5-ASA failure may discontinue 5-aminosalicylates 1, 2
• Regular monitoring of renal function is recommended for patients on long-term 5-ASA therapy: eGFR before starting, after 2-3 months, then annually 3

Steroid-Dependent Disease

• Patients requiring two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent, require treatment escalation with thiopurines (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day), anti-TNF therapy, vedolizumab, or tofacitinib 4, 3

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Important Considerations and Pitfalls

Medication Selection

• Sulfasalazine 2-4 g/day has a higher incidence of side effects compared with newer 5-ASA drugs but may be reasonable for selected patients with reactive arthropathy or when alternatives are cost-prohibitive 4, 1
• Olsalazine 1.5-3 g/day has a higher incidence of diarrhea in pancolitis and is best reserved for left-sided disease or 5-ASA intolerance 4

Monitoring and Safety

• Approximately 50% of patients experience short-term corticosteroid-related adverse events including acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia 3
• Screen for latent tuberculosis before initiating infliximab, and monitor closely for infections during treatment 5
• Lymphoma and other malignancies have been reported with TNF blockers, with particular concern for hepatosplenic T-cell lymphoma in young males receiving combination therapy with azathioprine or mercaptopurine 5

Treatment Response Timeline

• The median time to cessation of rectal bleeding is approximately 9 days with high-dose mesalazine (4.8 g/day) compared to 16 days with standard dose (2.4 g/day) 3
• Patients who do not respond to infliximab by week 14 are unlikely to respond with continued dosing and discontinuation should be considered 5

Not Recommended

• Probiotics, curcumin, and fecal microbiota transplantation are not currently recommended for routine use due to insufficient evidence 1