What are the medication options for a patient with extensive ulcerative colitis?

Medication Options for Extensive Ulcerative Colitis

For extensive (pancolitis) ulcerative colitis, start with high-dose oral mesalamine (4.8 g/day) combined with rectal mesalamine (at least 1 g/day as an enema), and if remission is not achieved within 10-14 days of rectal bleeding or 40 days total, add oral prednisone 40 mg/day or budesonide MMX 9 mg/day. 1

First-Line Therapy: 5-Aminosalicylates (5-ASA)

Oral Mesalamine Dosing

• Standard dose: 2.4-3 g/day for mild-to-moderate disease 2
• High dose: 4.8 g/day provides superior efficacy, particularly in extensive colitis, with remission rates significantly better than standard doses (RR 0.75 vs 0.84) 1
• Once-daily dosing is as effective as divided doses and improves adherence 2, 1

Combined Oral and Rectal Therapy

• Adding rectal mesalamine (≥1 g/day as enema) to oral mesalamine is superior to oral therapy alone for extensive colitis 2, 1
• This combination approach improves both clinical remission and mucosal healing rates 2

Alternative 5-ASA Formulations

• Sulfasalazine 2-4 g/day is effective but has higher side effect rates; may be appropriate in selected patients 2, 3
• Diazo-bonded 5-ASA (balsalazide 2-6.75 g/day, olsalazine 2-3 g/day) are alternatives to mesalamine 2

Second-Line Therapy: Corticosteroids

When to Escalate

• Escalate if insufficient response after 10-14 days of rectal bleeding or 40 days without complete remission 1

Corticosteroid Options

• Oral prednisone 40 mg/day is appropriate for moderate-to-severe disease 2, 1
• Budesonide MMX 9 mg/day is an alternative with fewer systemic side effects 2, 1
• Taper corticosteroids gradually over 8 weeks to avoid adrenal insufficiency 2, 1
• Intravenous methylprednisolone 40-60 mg/day for hospitalized patients with acute severe UC 2

Third-Line Therapy: Immunomodulators and Biologics

Indications for Advanced Therapy

• Corticosteroid-dependent disease (requiring repeated courses or inability to taper) 2
• Moderate-to-severe disease failing 5-ASA and corticosteroids 2

Biologic Agents

• TNF-α antagonists (infliximab): 5 mg/kg IV at weeks 0,2,6, then every 8 weeks for maintenance 2, 4
• Vedolizumab (integrin antagonist) 2
• Ustekinumab (IL-12/23 antagonist) 2
• The AGA suggests early use of biologics rather than gradual step-up in patients who value efficacy over the safety profile of 5-ASA 2

Immunomodulators

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day for steroid-dependent disease 1
• Combination therapy with biologics and immunomodulators may be considered, though risk of hepatosplenic T-cell lymphoma exists, particularly in young males 2, 4

Small Molecule Inhibitors

• Tofacitinib (JAK inhibitor) is an option for moderate-to-severe UC 2

Maintenance Therapy

Long-Term 5-ASA

• Lifelong maintenance with 5-ASA ≥2 g/day is recommended for all patients with extensive UC 2, 1
• Higher maintenance doses (2.4 g/day) prolong remission compared to lower doses (1.2 g/day) 2
• Discontinuing 5-ASA increases relapse risk; no tapering is required when stopping (unlike corticosteroids) 5

Maintenance After Biologic Induction

• Continue biologic therapy for maintenance after achieving remission 2
• The AGA suggests against continuing 5-ASA in patients on biologics/immunomodulators, though this recommendation is based on very low-quality evidence 2

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Initial Management

• IV methylprednisolone 40-60 mg/day (not higher doses) 2
• No adjunctive antibiotics unless infection is documented 2

Rescue Therapy for Steroid-Refractory Disease

• Infliximab or cyclosporine for patients failing IV corticosteroids after 3-5 days 2
• No clear recommendation on intensive vs. standard infliximab dosing in this setting 2

Critical Pitfalls to Avoid

• Underdosing mesalamine: Doses <2 g/day are significantly less effective (RR 0.88 vs 0.84 for ≥2 g/day) 1
• Oral monotherapy in extensive disease: Combined oral + rectal therapy is superior 2, 1
• Delayed escalation: Do not wait beyond 40 days without improvement before adding corticosteroids 1
• Abrupt corticosteroid discontinuation: Always taper over 8 weeks to prevent adrenal insufficiency 2, 1
• Ignoring tuberculosis screening: Test for latent TB before starting biologics and treat if positive 4
• Young males on combination therapy: Highest risk for hepatosplenic T-cell lymphoma with TNF-blocker + thiopurine combination 4

Monitoring Requirements

• Fecal calprotectin every 6-12 months in patients in remission; escalate therapy if elevated (>150 mg/g) 1
• Complete blood counts and liver function tests every 2 weeks for first 3 months on sulfasalazine, then monthly, then quarterly 3
• Renal function monitoring periodically on mesalamine due to rare interstitial nephritis risk 1