What is the best treatment plan for a middle-aged adult patient with a history of ulcerative colitis (UC) presenting with a moderate to severe flare-up characterized by abdominal pain, diarrhea, weight loss, and occasional hematochezia?

Critical Treatment Plan Modifications for Moderate-to-Severe UC Flare

Your Current Plan Requires Immediate Revision

Your patient with moderate-to-severe UC presenting with weight loss and hematochezia requires advanced therapy (biologics or JAK inhibitors), not just corticosteroids and mesalamine. 1 The 2024 AGA guidelines strongly recommend early use of advanced therapies rather than gradual step-up after failure of 5-aminosalicylates in patients with moderate-to-severe disease. 1

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Major Problems with Your Current Approach

1. Mesalamine is Insufficient for Moderate-to-Severe Disease

• Mesalamine 2400 mg BID is only FDA-approved and effective for mild-to-moderate UC. 2 Clinical trials showed remission rates of only 29-41% versus 13-22% for placebo in mild-to-moderate disease. 2
• Your patient has moderate-to-severe disease based on: weight loss, hematochezia, and a flare lasting months—these are high-risk features requiring advanced therapy. 1
• The AGA suggests stopping 5-aminosalicylates once patients escalate to advanced therapies or immunomodulators. 1 Continuing mesalamine adds no benefit and increases pill burden.

2. Corticosteroids Alone Cannot Maintain Remission

• While prednisone is appropriate for acute symptom control, corticosteroids should never be used for maintenance therapy. 3
• Your taper is reasonable for induction, but you must initiate advanced therapy concurrently to maintain remission after steroid withdrawal. 1
• Approximately 20% of UC patients require hospitalization, and corticosteroid-dependent disease predicts poor outcomes without advanced therapy. 1, 4

3. Missing Advanced Therapy Initiation

The 2024 AGA guidelines recommend the following advanced therapies for moderate-to-severe UC: 1

First-Line Options (Higher Efficacy in Biologic-Naïve Patients):

• Infliximab (strong recommendation) 1
• Vedolizumab (strong recommendation) 1
• Upadacitinib (strong recommendation, but FDA restricts to TNF-failure patients in the US) 1
• Ozanimod, etrasimod, risankizumab, guselkumab (strong recommendations) 1

Intermediate Efficacy Options:

• Golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab 1

Lower Efficacy (Avoid as First-Line):

• Adalimumab (conditional recommendation only; network meta-analysis shows inferiximab and vedolizumab are superior) 1

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Recommended Treatment Algorithm

Step 1: Initiate Corticosteroids for Acute Control

• Continue your prednisone taper as planned (40→30→20→10 mg over 5 weeks). 1

Step 2: Start Advanced Therapy Immediately

For biologic-naïve patients with moderate-to-severe UC, prefer infliximab or vedolizumab over adalimumab. 1

• Infliximab: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks. 3
• Vedolizumab: 300 mg IV at weeks 0,2,6, then every 8 weeks. 3
• Consider combination therapy: The AGA suggests combining TNF antagonists (infliximab) with an immunomodulator (azathioprine or 6-mercaptopurine) over monotherapy for enhanced efficacy. 1

If JAK inhibitors are preferred (e.g., patient preference for oral therapy):

• Tofacitinib or upadacitinib can be used, but FDA labeling restricts JAK inhibitors to patients with prior TNF antagonist failure or intolerance. 1
• In Europe, JAK inhibitors should be used cautiously as first-line in patients ≥65 years, smokers, or those with cardiovascular disease history. 1

Step 3: Discontinue Mesalamine

• Stop mesalamine once advanced therapy is initiated. 1 The AGA suggests against continuing 5-ASA after escalation to biologics or immunomodulators. 1

Step 4: Monitor Response

• Symptomatic response within 3 months. 1
• Symptomatic and biochemical remission (normal CRP/ESR, fecal calprotectin) within 3-6 months. 1
• Endoscopic improvement/remission within 6-12 months. 1

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Additional Considerations

Laboratory Monitoring

• Your CBC, CMP, ESR/CRP, and hemoccult are appropriate. 1
• Add fecal calprotectin to monitor mucosal inflammation. 5
• Monitor for C. difficile and CMV if symptoms worsen or fail to improve. 1

Thromboprophylaxis

• Consider thromboprophylaxis if the patient requires hospitalization or has severe disease activity. 6

Electrolyte Supplementation

• Daily electrolytes for 30 days are reasonable given chronic diarrhea, but address the underlying inflammation with advanced therapy. 1

Claritin for Allergies

• This is fine and unrelated to UC management. [@N/A@]

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Common Pitfalls to Avoid

1. Do not delay advanced therapy. Gradual step-up after 5-ASA failure increases risk of complications, hospitalization, and colectomy. 1, 3
2. Do not use thiopurine monotherapy for induction. The AGA suggests against this. 1
3. Do not use methotrexate monotherapy for UC. It is ineffective for induction or maintenance. 1
4. Do not continue corticosteroids for maintenance. They are for induction only. 3
5. Do not use antibiotics routinely. The British Society of Gastroenterology and ESPEN guidelines explicitly state antibiotics are not recommended for moderate-to-severe UC. 7

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Summary of Revised Plan

Immediate Actions:

1. Continue prednisone taper as planned. 1
2. Initiate infliximab or vedolizumab immediately. 1
3. Discontinue mesalamine. 1
4. Consider adding azathioprine or 6-mercaptopurine if using infliximab. 1
5. Monitor CBC, CMP, ESR/CRP, fecal calprotectin, and hemoccult. 1, 5
6. Reassess response at 3 months (symptoms), 3-6 months (biochemical remission), and 6-12 months (endoscopy). 1

This approach prioritizes morbidity, mortality, and quality of life by preventing disease progression, hospitalization, and colectomy. 1