What are the treatment options for ulcerative colitis?

Ulcerative Colitis Treatment

Treatment for ulcerative colitis is stratified by disease location and severity, with topical 5-ASA for proctitis, oral 5-ASA (2-4 g daily) combined with topical therapy for mild-to-moderate disease extending beyond the rectum, and prednisolone 40 mg daily for moderate-to-severe disease, escalating to advanced therapies (biologics or JAK inhibitors) if corticosteroids fail within 2 weeks or cannot be tapered. 1

Treatment Algorithm by Disease Location and Severity

Ulcerative Proctitis (Disease Limited to Rectum)

• First-line: Mesalamine 1 g suppository once daily is the preferred initial treatment, as it delivers medication directly to the rectum with better tolerability 2
• Second-line (if no response or intolerance): Add oral 5-ASA (2-4 g daily) or substitute topical corticosteroids 1
• Refractory proctitis: Consider oral corticosteroids, topical tacrolimus, JAK inhibitors, S1P agonists, or biologic therapy 1

Key point: Topical mesalamine is more effective than topical steroids for proctitis, and combination therapy (topical plus oral) outperforms monotherapy 2

Mild-to-Moderate Disease Extending Beyond Rectum

Left-Sided Disease (to Splenic Flexure)

• First-line: Aminosalicylate enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day 2
• Alternative oral options: Mesalamine 2-4 g daily, balsalazide 6.75 g daily, or olsalazine 1.5-3 g daily (though olsalazine has higher diarrhea incidence in pancolitis) 1
• Dosing preference: Once-daily oral mesalamine is preferred over multiple daily dosing for better adherence 2

Extensive Disease (Beyond Splenic Flexure)

• First-line: Oral 5-ASA 2-4 g daily, which can be combined with topical 5-ASA therapy 1
• Escalation if no response in 2-4 weeks: Initiate oral prednisolone 40 mg daily 1, 2
• High-dose option: For suboptimal response to standard-dose mesalamine, consider high-dose mesalamine (>3 g/day) with rectal mesalamine before advancing to corticosteroids 2

Critical timing: If no response to 5-ASA within 2-4 weeks, do not delay corticosteroid initiation 1

Moderate-to-Severe Ulcerative Colitis

• Induction therapy: Prednisolone 40 mg daily combined with 5-ASA 1, 2
• Alternative consideration: High-dose 5-ASA alone can be attempted, but corticosteroids must be initiated if no response within 2 weeks 1
• Steroid taper: Reduce prednisolone gradually over 8 weeks according to severity and patient response; more rapid reduction increases early relapse risk 1, 2
• Corticosteroid efficacy: Meta-analysis shows corticosteroids superior to placebo (RR of no remission 0.65; 95% CI 0.45-0.93), with 40 mg/day prednisolone more effective than 20 mg/day 1

Escalation criteria for advanced therapy: Start biologics or small molecule drugs if:

• No adequate response to oral corticosteroids within 2 weeks 1
• Unsuccessful corticosteroid taper 1
• Need to avoid repeated corticosteroid courses 1

Severe/Acute Severe Ulcerative Colitis

• Management approach: Joint management by gastroenterologist and colorectal surgeon with daily physical examination for abdominal tenderness and rebound 2
• Supportive care: Intravenous fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, administer subcutaneous heparin for thromboembolism prophylaxis 2
• Induction therapy: Intravenous corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) 2
• Rescue therapy for steroid-refractory disease: Infliximab or cyclosporine 2, 3

Advanced Therapies (Biologics and Small Molecules)

Indications for Advanced Therapy

• Corticosteroid-resistant or corticosteroid-dependent disease 2
• Failure to respond to corticosteroids within 2 weeks 1
• Chronic active disease requiring steroid-sparing agents 1

Biologic Options

Infliximab (Anti-TNF):

• Dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 3
• Dose escalation: For patients who respond then lose response, consider increasing to 10 mg/kg 3
• Response assessment: Patients not responding by week 14 are unlikely to respond with continued dosing and should discontinue 3
• FDA indication: Approved for reducing signs/symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in moderately to severely active UC with inadequate response to conventional therapy 3

Other biologics: Vedolizumab (anti-α4β7 integrin) and ustekinumab (anti-IL-12/IL-23) are alternatives 4

Small Molecule Options

• JAK inhibitors (e.g., tofacitinib) 4
• S1P modulators (e.g., ozanimod) 4

Important caveat: The highest response rates to advanced therapies range only 30-60% in clinical trials, and treatment selection requires consideration of patient factors, disease characteristics, prior treatment history, and local availability 1, 4

Maintenance Therapy

General Principles

• Continue successful induction agent for maintenance, with the critical exception that corticosteroids are NOT recommended for long-term maintenance 1
• Lifelong maintenance therapy is generally recommended, especially for left-sided or extensive disease, to reduce relapse risk and potentially colorectal cancer risk 2
• Treatment goal: Shift from clinical response to achieving remission assessed biochemically, endoscopically, and histologically to avoid long-term complications 1

Maintenance Options by Prior Induction

After 5-ASA induction:

• Continue 5-ASA therapy 1

After corticosteroid induction:

• Transition to 5-ASA, thiopurines (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day), anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 1, 2
• Purine analogues typically require induction with another agent (often corticosteroids) and are suggested alongside infliximab therapy 1

After biologic/immunomodulator induction:

• Continue the successful biologic or immunomodulator 2
• Patients in remission on biologics/immunomodulators after prior 5-ASA failure may discontinue 5-ASA 2

Special Considerations and Pitfalls

Sulfasalazine

• Higher side effect incidence compared to newer 5-ASA drugs 1
• May be reasonable for patients already in remission on sulfasalazine or with prominent arthritic symptoms if alternatives are cost-prohibitive 2

Monitoring and Surveillance

• Monitor symptoms and biomarkers of inflammation (e.g., fecal calprotectin) 4
• Colonoscopy at 8 years from diagnosis for dysplasia surveillance 4
• Adjust treatment if symptoms deteriorate, rectal bleeding persists beyond 10-14 days, or sustained relief not achieved after 40 days of appropriate 5-ASA therapy 2

Not Recommended

• Probiotics, curcumin, and fecal microbiota transplantation are not currently recommended for routine use due to insufficient evidence 2

Long-term Outcomes Despite Treatment

• Within 5 years of diagnosis, approximately 20% require hospitalization and 7% undergo colectomy 4
• Risk of colorectal cancer after 20 years is 4.5%, with 1.7-fold higher risk compared to general population 4
• Life expectancy is approximately 5 years shorter than people without UC 4