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 2, 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
• For suboptimal response, escalate to high-dose mesalamine (>3 grams daily) combined with rectal mesalamine 1, 4

Moderate-to-Severe Disease

When 5-ASA fails or disease is moderate-to-severe:

• Initiate oral corticosteroids (prednisolone 40 mg daily) for induction of remission 1, 3
• 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 for left-sided disease (not effective for extensive colitis), though no head-to-head trials exist comparing it to conventional steroids 2

For corticosteroid-dependent or refractory disease:

• Transition to advanced therapies: infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib, upadacitinib, ozanimod, etrasimod, risankizumab, or guselkumab 2
• The AGA strongly recommends these agents over no treatment for moderate-to-severe UC 2
• JAK inhibitors (tofacitinib, upadacitinib, filgotinib) are FDA-restricted to patients with prior TNF antagonist failure or intolerance in the United States 2
• Consider combining TNF antagonists with immunomodulators (thiopurines) rather than monotherapy for improved outcomes 2

Severe Ulcerative Colitis

Severe UC requires hospitalization and intensive management:

• Joint management by gastroenterologist and colorectal surgeon with daily physical examination for abdominal tenderness and rebound 1
• Intravenous fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, administer subcutaneous heparin for thromboembolism prophylaxis 1
• Intravenous corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) 1
• For IV steroid-refractory disease, use infliximab 5 mg/kg at weeks 0,2, and 6, or cyclosporine 2, 1, 5
• Second-line medical therapy with infliximab or cyclosporine is not associated with higher mortality 2

Maintenance Therapy

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

Maintenance regimens:

• After 5-ASA-induced remission: Continue mesalamine ≥2 grams daily 2
• After corticosteroid-induced remission: Transition to 5-ASA, thiopurines, anti-TNF agents (with or without immunomodulators), or vedolizumab 1
• After biologic induction: Continue biologic maintenance (e.g., infliximab 5 mg/kg every 8 weeks) 5
• Patients in remission on biologics/immunomodulators after 5-ASA failure may discontinue 5-ASA 2, 1

For combination therapy:

• Suggest combining TNF antagonists with immunomodulators rather than monotherapy 2
• In patients achieving corticosteroid-free remission for ≥6 months on combination therapy, suggest against withdrawing TNF antagonists 2

Important Caveats and Pitfalls

Avoid these common errors:

• Do not use repeated courses of corticosteroids even in mild-moderate disease; escalate therapy instead 4
• Patients who do not respond to infliximab by week 14 are unlikely to respond with continued dosing and should be considered for alternative therapy 5
• Thiopurine monotherapy is suggested against for inducing remission in active disease 2
• Methotrexate monotherapy is suggested against for both induction and maintenance 2
• Probiotics, curcumin, and fecal microbiota transplantation are not recommended for routine use due to insufficient evidence, though emerging data on FT shows promise 2, 1

Monitoring thresholds:

• If rectal bleeding persists beyond 10-14 days or sustained symptom relief is not achieved after 40 days of appropriate 5-ASA therapy, escalate treatment 1
• Extended induction regimens (up to 16 weeks) or dose escalation may be beneficial for certain advanced therapies in severe disease 2