What is the most appropriate medication to initiate for induction of remission in a 31-year-old male with type 1 diabetes mellitus (T1DM) and hypertension, presenting with moderate abdominal pain, bloody stools, and a diagnosis of ulcerative colitis (UC) with diffuse superficial continuous colonic inflammation proximal to the splenic flexure?

Oral Mesalamine 1000 mg Four Times Daily is the Most Appropriate Initial Treatment

For this patient with newly diagnosed moderate ulcerative colitis extending proximal to the splenic flexure, oral mesalamine (Pentasa) 1000 mg four times daily (total 4 g/day) should be initiated as first-line therapy for induction of remission. 1

Rationale for Treatment Selection

Disease Characteristics Guide Therapy Choice

This patient presents with:

• Moderate disease activity (3-4 bloody stools/day, mild anemia, normal vital signs, ESR only mildly elevated) 1
• Extensive disease (inflammation proximal to splenic flexure) 1
• Treatment-naïve status (new diagnosis, no prior therapy) 1

These features make him an ideal candidate for high-dose oral 5-ASA therapy as initial treatment. 1

Why High-Dose Oral Mesalamine (4 g/day)

Oral mesalamine 2-4 g/day is recommended as effective first-line therapy for mild-to-moderate extensive ulcerative colitis. 1 The 2019 AGA guidelines specifically state that oral 5-ASAs are the preferred treatment for most patients with mild-moderate UC. 1

• High-dose mesalamine (≥4 g/day) leads to higher response rates and earlier symptom relief compared to conventional doses 2
• The 2025 British Society of Gastroenterology guidelines strongly recommend oral 5-ASA 2-3 g/day, with dose escalation to 4-4.8 g/day for patients flaring on standard doses 1
• Starting at 4 g/day is appropriate for this moderate presentation to optimize initial response 1, 2

Why NOT the Other Options

Mesalamine enema (Rowasa): While topical therapy is highly effective, enema preparations are unlikely to reach proximal to the sigmoid colon. 1 This patient has disease extending proximal to the splenic flexure, making rectal therapy alone inadequate. 1 Enemas would be appropriate as adjunctive therapy combined with oral mesalamine for enhanced efficacy, but not as monotherapy. 1

Budesonide 9 mg daily: Although FDA-approved for mild-to-moderate UC 3 and shown to be more effective than placebo 1, budesonide has critical limitations:

• Not superior to mesalamine for induction of remission 1
• Unsuitable for maintenance therapy due to lack of long-term efficacy/safety data and potential corticosteroid-related adverse effects 1
• The 2019 AGA guidelines explicitly state that "the lack of superiority over 5-ASA for induction of remission...make oral 5-ASAs the preferred treatment for most patients with mild-moderate UC" 1
• Should be reserved for patients who fail or are intolerant to 5-ASA therapy 1

Adalimumab: Biologic therapy is premature for this treatment-naïve patient with moderate disease. 1 The 2020 AGA guidelines on moderate-to-severe UC recommend early use of biologics for patients "at high risk of colectomy" or with more severe disease. 1 This patient has:

• Stable vital signs (pulse 88, afebrile) 1
• Hemoglobin 12.0 g/dL (only mild anemia) 1
• ESR 16 mm/hr (minimally elevated) 1

These parameters indicate moderate, not severe disease. Biologics should be reserved for patients who fail 5-ASA therapy or have severe disease requiring hospitalization. 1

Treatment Algorithm and Monitoring

Initial Management

• Start oral mesalamine 4 g/day (1000 mg four times daily) 1, 2
• Consider adding mesalamine enema 4 g rectally at bedtime for enhanced efficacy, as combination oral and rectal therapy leads to faster and higher remission rates 1, 2

Expected Timeline

• Assess response within 2 weeks 2
• If no improvement by 2 weeks, augment with oral corticosteroids (prednisolone 40 mg daily) 1, 2

Treatment Escalation Pathway

If inadequate response to optimized 5-ASA therapy (oral + rectal):

1. Prednisolone 40 mg daily tapered over 6-8 weeks 1
2. If steroid-dependent or steroid-refractory: advance to biologic therapy (infliximab, vedolizumab, adalimumab) or JAK inhibitors (tofacitinib) 1

Critical Pitfalls to Avoid

Do not start with corticosteroids in treatment-naïve moderate disease. While prednisolone is superior to 5-ASA for induction 1, it should be reserved for patients who fail 5-ASA therapy due to significant adverse effects and inability to use for maintenance. 1

Do not use budesonide as first-line therapy. Despite being a topically-acting corticosteroid with lower systemic effects, it offers no advantage over mesalamine and cannot be used long-term. 1

Monitor for diabetes complications. This patient has type 1 diabetes, which shares complications with UC (neuropathy, hepatic steatosis, thrombosis) and represents a risk factor for postoperative complications if surgery becomes necessary. 4 Avoid corticosteroids initially to prevent glucose dysregulation. 4

Ensure adequate dosing. Starting with suboptimal doses (e.g., 2 g/day) may lead to treatment failure and unnecessary escalation to corticosteroids. 1, 2