What is the recommended treatment for ulcerative colitis?

Treatment of Ulcerative Colitis

Initial Treatment Based on Disease Severity and Location

For mild-to-moderate ulcerative colitis, start with 5-aminosalicylates (5-ASA/mesalamine) at standard doses of 2-3 grams daily, escalating to advanced therapies (biologics or JAK inhibitors) for moderate-to-severe disease or steroid-dependent/refractory cases. 1

Mild-to-Moderate Disease by Location

Proctitis (rectal disease only):

• Use mesalamine 1-gram suppositories once daily as first-line therapy, which delivers medication more effectively to the rectum than oral formulations 1
• Topical mesalamine is more effective than topical corticosteroids 2
• Combining topical with oral mesalamine provides superior outcomes compared to monotherapy 1

Left-sided colitis:

• Combine aminosalicylate enema ≥1 gram daily with oral mesalamine ≥2.4 grams daily, which is more effective than either topical or oral therapy alone 2, 1
• Once-daily dosing is as effective as divided doses and improves adherence 2, 1

Extensive/pancolitis:

• Start with standard-dose mesalamine 2-3 grams daily or diazo-bonded 5-ASA 1, 3
• Add rectal mesalamine to oral therapy for better outcomes 1
• If suboptimal response, escalate to high-dose mesalamine (>3 grams daily) with rectal mesalamine 1, 3

Moderate-to-Severe Disease

For patients not responding to optimized 5-ASA therapy or those with moderate-to-severe activity:

• Initiate oral prednisolone 40 mg daily for induction of remission 1, 4
• Oral beclomethasone dipropionate is non-inferior to prednisone but not better tolerated 2
• Budesonide MMX 9 mg daily can be considered as an alternative to conventional steroids, particularly for left-sided disease, though head-to-head comparisons with conventional steroids are lacking 2

After corticosteroid-induced remission, transition to maintenance therapy with:

• 5-ASA for mild disease 1
• Thiopurines (though evidence is limited) 2
• Anti-TNF agents (infliximab, adalimumab, golimumab) with or without immunomodulators 2, 1
• Non-TNF biologics (vedolizumab, ustekinumab, risankizumab, guselkumab) 2
• JAK inhibitors (tofacitinib, upadacitinib, filgotinib) - FDA recommends use after TNF antagonist failure 2
• S1P modulators (ozanimod, etrasimod) 2

Severe Ulcerative Colitis

Severe disease requires hospital admission and joint management by gastroenterology and colorectal surgery:

• Administer intravenous corticosteroids (hydrocortisone 400 mg daily or methylprednisolone 60 mg daily) 2, 1
• Provide IV fluid and electrolyte replacement 1
• Maintain hemoglobin >10 g/dL 1
• Give subcutaneous heparin to reduce thromboembolism risk 1
• Perform daily physical examination for abdominal tenderness and rebound 1

For acute severe UC refractory to IV corticosteroids:

• Consider infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks 2, 5
• Alternatively, cyclosporine may be used 2, 1
• Second-line medical therapy with infliximab or cyclosporine is not associated with higher mortality 2

Advanced Therapy Selection for Moderate-to-Severe Disease

The AGA strongly recommends the following agents over no treatment (listed by strength of recommendation):

Strong recommendations (high certainty evidence):

• Infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab 2

Conditional recommendations (moderate certainty evidence):

• Adalimumab, filgotinib, and mirikizumab 2

Key implementation considerations:

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs 2
• Subcutaneous formulations of infliximab and vedolizumab show comparable efficacy to IV maintenance 2
• Extended induction regimens (up to 16 weeks) or dose escalation may benefit patients with severe disease 2
• JAK inhibitors have restricted first-line use in the US (FDA recommends after TNF failure) and in Europe (caution in patients ≥65 years, smokers, cardiovascular disease history, cancer history) 2

Combination Therapy with Immunomodulators

For TNF antagonists, combine with immunomodulators (thiopurines or methotrexate) rather than monotherapy 2

For non-TNF biologics, there is insufficient evidence to recommend combination therapy over monotherapy 2

Thiopurine monotherapy:

• Suggest against using for induction of remission in active disease 2
• May be used for maintenance after corticosteroid-induced remission, though evidence is limited 2

Methotrexate monotherapy:

• Suggest against using for either induction or maintenance 2

Maintenance Therapy

Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease, to reduce relapse risk and potentially colorectal cancer risk 2, 1

Maintenance dosing considerations:

• Higher doses of 5-ASA (≥2 grams daily) are more effective than lower doses for maintaining remission 2
• Patients with extensive disease benefit most from dose escalation 2
• Once-daily dosing improves compliance without sacrificing efficacy 2, 1

For patients in remission on biologics/immunomodulators after 5-ASA failure:

• Discontinue 5-ASA as it provides no additional benefit 2, 1

For patients in corticosteroid-free remission ≥6 months on combination TNF antagonist + immunomodulator therapy:

• Suggest against withdrawing TNF antagonist 2
• Insufficient evidence to recommend for or against withdrawing immunomodulator 2

Special Considerations and Caveats

Sulfasalazine:

• May be considered for patients already in remission on this agent or those with prominent arthritic symptoms, particularly when cost is prohibitive 1
• Has higher intolerance rates than mesalamine formulations 6
• Requires doses of 2-4 grams daily 1

Therapies NOT recommended:

• Probiotics (including VSL#3) - insufficient evidence despite some positive signals 2, 1
• Curcumin - insufficient evidence 1
• Fecal microbiota transplantation - encouraging proof-of-concept data but protocol optimization needed 2, 1
• Helminth therapy - insufficient evidence 2

Common pitfalls to avoid:

• Do not use repeated courses of corticosteroids; escalate to steroid-sparing maintenance therapy 1
• Do not continue 5-ASA in patients on biologics after 5-ASA failure 2, 1
• Do not delay escalation in patients with inadequate response to optimized 5-ASA therapy 1
• Monitor for response within 10-14 days for rectal bleeding and 40 days for complete symptom relief on 5-ASA; introduce steroids if inadequate response 1