What is the recommended treatment for ulcerative colitis?

Treatment of Ulcerative Colitis

For mild-to-moderate ulcerative colitis, start with oral mesalamine at 2.4-3 grams daily combined with topical mesalamine (1 gram enema or suppository depending on disease location), and escalate to corticosteroids or advanced therapies (infliximab, vedolizumab, ustekinumab, JAK inhibitors) for moderate-to-severe disease or failure of aminosalicylates. 1, 2

Treatment Algorithm by Disease Severity and Location

Mild-to-Moderate Disease

Proctitis (rectal involvement only):

• First-line: Mesalamine 1-gram suppository once daily 2
• Topical mesalamine is more effective than topical steroids 1
• If inadequate response, add oral mesalamine ≥2.4 g/day to topical therapy 1, 2

Left-sided colitis:

• First-line: Mesalamine enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day 1, 2
• This combination is more effective than either oral or topical aminosalicylates alone 1
• Once-daily dosing is as effective as divided doses and improves adherence 1, 2

Extensive/pancolitis:

• First-line: Oral mesalamine 2-3 grams/day (standard dose) 2, 3
• Add rectal mesalamine 1 g/day for better outcomes 2
• Consider once-daily dosing for adherence 2, 3

Escalation for suboptimal response:

• Increase to high-dose mesalamine (>3 grams/day) with rectal mesalamine 2, 3
• If still inadequate after optimized 5-ASA therapy, initiate oral prednisolone 40 mg daily 2, 4
• Alternative: Budesonide MMX 9 mg/day for left-sided disease (not effective for extensive colitis) 1

Moderate-to-Severe Disease

Corticosteroid induction:

• Oral prednisolone 40 mg daily for induction of remission 2
• Oral beclomethasone dipropionate is non-inferior to prednisone but not better tolerated 1
• After successful induction, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents, or vedolizumab 2

Advanced therapies (first-line for moderate-to-severe disease):

• Strong recommendation: Infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, or guselkumab 1
• Conditional recommendation: Adalimumab, filgotinib, or mirikizumab 1
• Infliximab dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks maintenance 5
• For corticosteroid-resistant or dependent disease, use anti-TNF therapy or vedolizumab 2

Important FDA restriction: JAK inhibitors (tofacitinib, filgotinib, upadacitinib) are recommended only after prior failure or intolerance to TNF antagonists in the United States 1

Severe Ulcerative Colitis

Immediate management:

• Joint management by gastroenterologist and colorectal surgeon 2
• Hospital admission for intensive treatment 1, 2
• IV fluid and electrolyte replacement 2
• Maintain hemoglobin >10 g/dL 2
• Subcutaneous heparin to reduce thromboembolism risk 2
• Daily physical examination for abdominal tenderness and rebound 2

Medical therapy:

• IV corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) 2
• For IV corticosteroid-refractory disease: Infliximab or cyclosporine 1, 2
• Second-line medical therapy with infliximab or cyclosporine is not associated with higher mortality 1

Maintenance Therapy

Lifelong maintenance is recommended for:

• All patients with left-sided or extensive disease 1, 2
• Patients with distal disease who relapse more than once yearly 2

Maintenance dosing:

• Mesalamine ≥2 g/day for maintenance (higher doses prolong remission better than 1.2 g/day) 1
• Time in remission is longer when maintenance dose is increased from 1.2 to 2.4 g/day, with extensive disease benefiting most 1

De-escalation considerations:

• Patients in remission on biologics/immunomodulators after prior 5-ASA failure may discontinue 5-ASA 1, 2
• Do not withdraw TNF antagonists in patients achieving corticosteroid-free remission for ≥6 months on combination therapy 1

Combination Therapy

TNF antagonists with immunomodulators:

• Combining TNF antagonists with immunomodulators is preferred over monotherapy 1
• However, hepatosplenic T-cell lymphoma risk exists, particularly in adolescent/young adult males receiving azathioprine or 6-mercaptopurine with TNF blockers 5

Immunomodulator monotherapy:

• Suggest against thiopurine monotherapy for inducing remission in active disease 1
• May consider thiopurine monotherapy for maintaining corticosteroid-induced remission 1
• Suggest against methotrexate monotherapy for induction or maintenance 1

Common Pitfalls and Caveats

Avoid these errors:

• Do not use low-dose mesalamine (<2.4 g/day) for extensive disease—it is less effective 1, 2
• Do not use repeated courses of corticosteroids; escalate to steroid-sparing therapy instead 2
• Do not continue patients beyond 14 weeks on infliximab if no response—they are unlikely to respond 5
• Do not use non-MMX budesonide for UC—it is not effective 1

Special populations:

• Sulfasalazine 2-4 g/day may be considered for patients with prominent arthritic symptoms or cost concerns, despite higher intolerance rates 2, 3
• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs 1

Emerging therapies with insufficient evidence:

• Probiotics (including VSL#3) show some benefit but significant heterogeneity between trials 1
• Fecal microbiota transplantation shows promise (27% vs 8% remission with placebo) but optimal protocol undefined 1
• Curcumin and helminth therapy lack sufficient evidence for routine use 2

Cancer prevention:

• Mesalamine ≥1.2 g/day and sulfasalazine ≥2 g/day may reduce colorectal cancer risk in UC patients 1, 6
• Colonoscopy surveillance required at 8 years from diagnosis 7