What is the best management approach for a patient with ulcerative colitis?

Management of Ulcerative Colitis

The best management of ulcerative colitis requires stratification by disease severity and extent, with mild-to-moderate distal disease treated with combination topical mesalazine 1g daily plus oral mesalazine 2-4g daily, moderate-to-severe disease requiring advanced therapies (anti-TNF agents, vedolizumab, ustekinumab, JAK inhibitors), and severe disease necessitating intravenous corticosteroids with early surgical consultation if no response by day 3. 1, 2

Disease Severity Assessment and Classification

Before initiating therapy, confirm disease activity endoscopically and exclude infectious causes, though treatment should not be delayed awaiting stool culture results in severe presentations 2, 1. Disease extent determines initial therapy:

• Distal colitis: Disease up to sigmoid-descending junction 3
• Left-sided disease: Extends to splenic flexure 3
• Extensive disease: Extends proximal to splenic flexure 3

Monitor disease activity using stool frequency, rectal bleeding, inflammatory markers (CRP, fecal calprotectin), and endoscopic assessment 2, 1.

Mild-to-Moderate Disease Management

Distal/Left-Sided Disease

First-line therapy is combination topical mesalazine 1g daily (once-daily dosing preferred) plus oral mesalazine 2-4g daily, which achieves superior remission rates compared to monotherapy. 1, 3 Do not switch between different oral 5-ASA formulations if initial therapy fails, as this is ineffective 1.

For patients intolerant to topical mesalazine, use topical corticosteroids as second-line therapy 2, 4.

Extensive Disease

Oral mesalazine 2-4g daily or balsalazide 6.75g daily as first-line therapy 3. If inadequate response after appropriate trial, escalate to oral prednisolone 40mg daily, tapered gradually over 8 weeks 2, 3. Rapid steroid tapering is associated with early relapse and must be avoided 2, 4.

Common pitfall: Inadequate drug delivery due to proximal constipation—obtain abdominal X-ray to assess for fecal loading and add laxatives if present 2, 4.

Moderate-to-Severe Disease Management

For moderate-to-severe UC (Mayo endoscopy subscore 2-3, high inflammatory burden, or steroid-dependent disease), advanced therapies are strongly recommended over conventional therapy alone. 1

Biologic and Small Molecule Options

• Anti-TNF agents (infliximab, adalimumab, golimumab): Infliximab 5mg/kg IV at weeks 0,2,6, then every 8 weeks 5
• Vedolizumab: Anti-integrin therapy 2, 1
• Ustekinumab: Anti-IL-12/23 agent 1, 6
• JAK inhibitors (tofacitinib, upadacitinib): Reserved for patients who failed or are intolerant to anti-TNF agents 1

Combination therapy with anti-TNF plus thiopurines (azathioprine 2mg/kg/day) or methotrexate is superior to monotherapy for inducing remission. 2, 1 The UC-SUCCESS trial demonstrated 39.7% achieved corticosteroid-free remission with infliximab plus azathioprine versus 22.1% with infliximab alone 2.

Steroid-Dependent Disease

Patients requiring steroids to maintain remission should receive thiopurines, anti-TNF agents (preferably combined with thiopurines), vedolizumab, or methotrexate 2. Azathioprine is significantly more effective than 5-ASA for achieving clinical and endoscopic remission in steroid-dependent UC 2.

Acute Severe Ulcerative Colitis

Severe UC (Truelove and Witts criteria: ≥6 bloody stools daily, fever, tachycardia, anemia, elevated ESR) requires immediate hospitalization with joint gastroenterology-surgical management. 2

Initial Management Protocol

• Intravenous corticosteroids: Methylprednisolone 60mg every 24 hours or hydrocortisone 100mg four times daily 2, 1. Higher doses offer no benefit; lower doses are less effective 2.
• Daily monitoring: Physical examination for tenderness/rebound, vital signs four times daily, stool chart, FBC/ESR/CRP/electrolytes/albumin every 24-48 hours 2
• Daily abdominal radiography if colonic dilatation (transverse colon >5.5cm) detected 2
• IV fluid and electrolyte replacement with potassium supplementation ≥60 mmol/day 1
• Blood transfusion to maintain hemoglobin >10 g/dl (>8-10 g/dl) 2
• Subcutaneous low-molecular-weight heparin for thromboprophylaxis (rectal bleeding is not a contraindication) 2, 1
• Nutritional support if malnourished (enteral preferred over parenteral) 2
• Avoid anticholinergics, antidiarrheals, NSAIDs, and opioids (risk of toxic megacolon) 2

Response Assessment and Salvage Therapy

Assess response by day 3—approximately 67% respond to IV corticosteroids alone. 2, 1 Treatment duration should not exceed 7-10 days, as prolonged courses carry no additional benefit and increase toxicity 2, 1.

For non-responders by day 3-5, initiate salvage therapy:

• Infliximab 5mg/kg IV 2, 5
• Ciclosporin 2mg/kg/day IV 2
• Tacrolimus 2

If no improvement after 4-7 days of salvage therapy, proceed to colectomy 2. Critical warning: Prolonged observation increases risk of toxic megacolon and perforation with very high mortality 7. Patients should be informed of 25-30% chance of requiring colectomy 2.

Surgical Indications

Absolute indications: Toxic megacolon, perforation, severe colorectal bleeding 8. Relative indications: Deterioration during medical therapy, no response to salvage therapy by day 7 2, 8, 7.

Recommended procedure: Subtotal colectomy with ileostomy and rectal preservation (reconstruction deferred 6 months) 8, 7. Approximately 20-29% of acute severe UC patients require colectomy during admission, with overall mortality 1% (higher in patients >60 years) 1.

Maintenance Therapy

Lifelong maintenance therapy is generally recommended for all patients, especially those with left-sided or extensive disease, to reduce relapse risk and potentially reduce colorectal cancer risk. 2, 4, 3

Maintenance Options

• Aminosalicylates: Mesalazine ≥2g/day 1, 3
• Thiopurines: Azathioprine 1.5-2.5mg/kg/day or mercaptopurine 0.75-1.5mg/kg/day 2, 1, 4
• Biologics: Continue if in remission; for patients on combination therapy (TNF antagonist + immunomodulator) in corticosteroid-free remission ≥6 months, do not withdraw TNF antagonist 1

Discontinuation may be reasonable for distal disease in remission for 2 years in patients averse to medication, though maintenance therapy reduces colorectal cancer risk 2. For patients in remission on biologics and/or immunomodulators, discontinuing 5-ASA provides no additional benefit 3.

Refractory Disease Management

For endoscopically documented active disease failing oral corticosteroids combined with oral and rectal 5-ASA, consider IV steroid therapy, oral/rectal ciclosporin, oral/rectal tacrolimus, or infliximab 2. Up to 10% of patients undergoing colectomy have only distal disease; outcome of colectomy and pouch formation for distal UC is usually good 2.

Key principle: Surgery should be viewed as complementary to medical treatment, not a last resort—it can prevent complications, improve quality of life, and be life-saving 8.