What is the treatment guideline for ulcerative colitis?

Treatment Guidelines for Ulcerative Colitis

Disease Severity-Based Treatment Algorithm

For mild-to-moderate ulcerative colitis, initiate standard-dose mesalamine (2-3 grams/day) combined with rectal mesalamine as first-line therapy; for moderate-to-severe disease, use biologic agents (infliximab or vedolizumab preferred) with or without immunomodulators, rather than gradual step-up therapy after 5-ASA failure. 1, 2

Mild-to-Moderate Disease

Initial Therapy:

• Standard-dose mesalamine 2-3 grams/day is preferred over low-dose mesalamine or sulfasalazine 2
• Add rectal mesalamine to oral 5-ASA for superior outcomes - the combination is more effective than monotherapy 2
• Once-daily dosing is preferred over multiple daily dosing to improve adherence 2
• For suboptimal response, escalate to high-dose mesalamine (>3 grams/day) with rectal mesalamine before considering other agents 2

Disease Location-Specific Approach:

• Proctitis: Mesalamine 1-gram suppository once daily is the preferred initial treatment, as it delivers drug more effectively to the rectum 2
• Left-sided UC: Aminosalicylate enema ≥1 gram/day combined with oral mesalamine ≥2.4 grams/day is more effective than monotherapy 2
• Topical mesalamine is more effective than topical steroids for proctitis 2

Moderate-to-Severe Disease

Biologic Therapy Selection:

• Infliximab and vedolizumab are preferred first-line biologics in biologic-naïve patients over standard-dose adalimumab or golimumab 1
• Approved biologics include: infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab 1
• Tofacitinib (JAK inhibitor) is also approved for induction and maintenance 1

Infliximab Dosing (FDA-Approved):

• 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 3
• For adults who initially respond but lose response, consider increasing to 10 mg/kg 3
• Patients who do not respond by week 14 are unlikely to respond and should discontinue 3

Combination vs. Monotherapy:

• Combination therapy (biologic + immunomodulator) is more effective than monotherapy with either agent alone 1
• Combination infliximab and thiopurines achieved superior corticosteroid-free remission (RR 1.70,95% CI 1.04-2.78) compared to thiopurine monotherapy 1
• However, patients with less severe disease or those averse to side effects may opt for monotherapy 1

Critical Caveat: The evidence for combination therapy is moderate quality for infliximab but low quality for other biologics due to lack of direct trials 1. The risk of hepatosplenic T-cell lymphoma with combination therapy, particularly in young males with IBD on azathioprine/6-mercaptopurine, must be carefully weighed 3.

Corticosteroid Use

When to Use Steroids:

• Oral prednisolone 40 mg daily is appropriate for induction in moderate-to-severe UC 2
• After successful induction, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents, or vedolizumab 2
• For corticosteroid-resistant or dependent UC, use anti-TNF therapy or vedolizumab 2

Important Principle: Corticosteroids are for induction only, never for maintenance therapy 2.

Early Biologic Strategy

For patients with moderate-severe disease at high risk of colectomy, use biologics with or without immunomodulators early rather than gradual step-up after 5-ASA failure 1. This recommendation is based on the principle that delaying effective treatment increases risk of UC-related complications, hospitalization, colectomy, and inferior quality of life 1.

Exception: Patients with less severe disease who prioritize the safety profile of 5-ASA over biologic efficacy may reasonably choose 5-ASA first 1.

Prior Biologic Exposure

In patients with prior infliximab exposure, particularly primary non-responders, vedolizumab or tofacitinib are preferred over adalimumab or golimumab 1. This reflects the importance of switching mechanism of action after primary failure.

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Management Approach:

• Joint management by gastroenterologist and colorectal surgeon is mandatory with daily physical examination for abdominal tenderness and rebound 2
• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) is the mainstay after excluding alternative etiologies 1, 2
• Provide IV fluid and electrolyte replacement, maintain hemoglobin >10 g/dL, and administer subcutaneous heparin to reduce thromboembolism risk 2
• Routine adjunctive antibiotics are not recommended in patients without documented infections 1

Steroid-Refractory Disease:

• After 3-5 days of IV corticosteroids without response, use either infliximab or cyclosporine for patients preferring ongoing medical management 1, 2
• No recommendation can be made for intensive vs. standard infliximab dosing in this setting 1

Maintenance Therapy

Long-Term Management:

• Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease 2
• Patients in remission on biologics and/or immunomodulators after prior 5-ASA failure may discontinue 5-ASA 1, 2

Agents NOT Recommended:

• Thiopurine monotherapy should not be used for induction but may be considered for maintenance 1
• Methotrexate monotherapy (oral or subcutaneous) should not be used for induction or maintenance 1
• Probiotics, curcumin, and fecal microbiota transplantation are not recommended due to insufficient evidence 2

Pediatric Considerations

For pediatric patients ≥6 years with moderate-to-severe UC:

• Infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks is FDA-approved 3
• Same dosing applies for both Crohn's disease and ulcerative colitis in this age group 3

Critical Warning: Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers 3. Hepatosplenic T-cell lymphoma risk is particularly elevated in adolescent and young adult males with IBD receiving combination therapy with azathioprine or 6-mercaptopurine 3.

Safety Monitoring

Before Initiating Biologics:

• Test for latent tuberculosis; if positive, initiate treatment before starting biologic 3
• Monitor all patients for active TB during treatment, even if initial test was negative 3
• Consider empiric antifungal therapy for patients at risk of invasive fungal infections who develop severe systemic illness 3

During Treatment:

• Discontinue biologic if serious infection develops 3
• Close monitoring for signs and symptoms of infection is required throughout treatment 3