What is the recommended treatment approach for a patient with ulcerative colitis?

Treatment of Ulcerative Colitis

The treatment approach for ulcerative colitis must be stratified by disease severity and extent: mild-to-moderate disease requires 5-aminosalicylates as first-line therapy with combination oral and rectal formulations, while moderate-to-severe disease demands advanced therapies including infliximab, vedolizumab, or JAK inhibitors, with infliximab and vedolizumab preferred as first-line biologics in treatment-naïve patients. 1, 2, 3

Disease Severity Classification and Initial Assessment

Before initiating therapy, confirm disease activity endoscopically and exclude infectious causes, though treatment should not be delayed in severe presentations 4. Disease extent determines the therapeutic approach:

• Distal colitis: Disease up to the sigmoid-descending junction 4
• Left-sided disease: Extends to the splenic flexure 4
• Extensive disease: Extends proximal to the splenic flexure 4

Monitor disease activity using stool frequency, rectal bleeding, inflammatory markers (CRP, fecal calprotectin), and endoscopic assessment 4.

Mild-to-Moderate Ulcerative Colitis

Extensive Disease (Beyond Splenic Flexure)

Start with standard-dose mesalamine 2-3 grams/day orally combined with rectal mesalamine rather than low-dose mesalamine or sulfasalazine 1, 2. This combination achieves superior remission rates compared to monotherapy 2, 3.

• Use once-daily dosing of oral mesalamine for better adherence 1
• If suboptimal response to standard dosing or moderate disease activity, escalate to high-dose mesalamine (>3 grams/day) with rectal mesalamine 1, 2
• Patients already on sulfasalazine in remission or with prominent arthritic symptoms may continue sulfasalazine 2-4g/day if cost is prohibitive, despite higher intolerance rates 1, 5

Distal Disease (Proctosigmoiditis or Proctitis)

For proctitis, initiate mesalamine 1-gram suppository once daily as it delivers medication more effectively to the rectum 2. For proctosigmoiditis, use mesalamine enemas rather than oral mesalamine 1.

• Topical mesalamine is more effective than topical steroids 2
• If intolerant to mesalamine suppositories, use rectal corticosteroid foam preparations 1

Escalation for Inadequate Response

If patients fail optimized oral and rectal 5-ASA therapy (after 40 days), add oral prednisolone 40 mg daily or budesonide MMX 1, 2. However, standard-dose oral mesalamine is preferred over budesonide MMX for initial induction 1.

Moderate-to-Severe Ulcerative Colitis

First-Line Advanced Therapy Selection

The AGA strongly recommends infliximab and vedolizumab as preferred first-line biologics in biologic-naïve patients 1, 3. Other options with strong recommendations include golimumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab 1.

Critical FDA restriction: JAK inhibitors (tofacitinib, upadacitinib, filgotinib) should only be used in patients with prior failure or intolerance to TNF antagonists 1. The European Medicine Agency additionally recommends cautious use in patients ≥65 years, current/previous smokers, or those with cardiovascular disease or cancer history 1.

Combination Therapy Strategy

Combine TNF antagonists with immunomodulators (thiopurines or methotrexate) rather than using TNF antagonist monotherapy 1, 3. This combination is more effective than monotherapy for inducing remission 1.

• For non-TNF biologics (vedolizumab, ustekinumab), there is insufficient evidence to recommend combination therapy over monotherapy 1
• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs 1

Dosing Considerations

Infliximab dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 6. For patients who respond then lose response, consider escalating to 10 mg/kg 6. Patients not responding by week 14 are unlikely to benefit from continued dosing 6.

Extended induction regimens (up to 16 weeks) or dose escalation may benefit patients with severe disease 1.

Corticosteroid Bridge Therapy

For moderate-to-severe disease requiring immediate symptom control, use oral prednisolone 40 mg daily as a bridge to advanced therapies 2, 3. After successful induction, transition to maintenance with 5-ASA, thiopurines, anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 2.

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Severe UC requires joint management by gastroenterology and colorectal surgery with daily physical examination for abdominal tenderness and rebound 2, 3, 4.

Immediate Management Protocol

• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) 3, 4
• IV fluid and electrolyte replacement 2, 3
• Maintain hemoglobin >10 g/dL with transfusion if needed 2, 3
• Subcutaneous low-molecular-weight heparin for thromboprophylaxis 2, 3, 4
• Daily abdominal radiography 4

Assessment and Rescue Therapy

Assess response by day 3—approximately 67% respond to IV corticosteroids alone 4. For patients refractory to IV corticosteroids, use infliximab or cyclosporine 2, 4.

Maintenance Therapy

Lifelong maintenance therapy is recommended for all patients, especially those with left-sided or extensive disease, to reduce relapse risk and potentially reduce colorectal cancer risk 2, 3, 4.

Maintenance Options by Prior Treatment

• Patients in remission on biologics/immunomodulators after prior 5-ASA failure may discontinue 5-ASA 2, 3, 4
• For patients on combination TNF antagonist plus immunomodulator therapy in corticosteroid-free remission for ≥6 months: do not withdraw TNF antagonist 1
• Insufficient evidence exists to recommend withdrawing immunomodulators versus continuing combination therapy 1

Immunomodulator Monotherapy

Avoid thiopurine monotherapy for inducing remission in active disease 1. However, thiopurine monotherapy may be used for maintaining remission typically induced with corticosteroids 1. Avoid methotrexate monotherapy for both induction and maintenance 1.

Common Pitfalls and Safety Considerations

Infection Screening Before Biologics

Screen for latent tuberculosis and initiate treatment before starting infliximab or other TNF antagonists 6. Monitor for invasive fungal infections (histoplasmosis, coccidioidomycosis), bacterial infections (Legionella, Listeria), and opportunistic infections 6.

Malignancy Risk

Hepatosplenic T-cell lymphoma, though rare, has been reported in patients receiving TNF blockers with concomitant azathioprine or 6-mercaptopurine, particularly in adolescent and young adult males with Crohn's disease or ulcerative colitis 6. Weigh this risk when considering combination therapy in this demographic.

Therapies NOT Recommended

Do not use probiotics, curcumin, or fecal microbiota transplantation due to insufficient evidence—their use risks delaying proven effective therapy 1, 2.

Monitoring Requirements

For patients on sulfasalazine: perform complete blood counts with differential, liver function tests every 2 weeks for the first 3 months, then monthly for the second 3 months, then every 3 months 5. Monitor urinalysis and renal function periodically 5.