What is the most appropriate medication to initiate for induction of remission in a patient with moderate ulcerative colitis (UC)?

Management of Moderate Ulcerative Colitis: First-Line Therapy

For a 31-year-old male with moderate ulcerative colitis extending proximal to the splenic flexure, oral mesalamine (Pentasa) 1000 mg four times daily is the most appropriate medication to initiate for induction of remission.

Disease Assessment and Classification

SJ presents with:

• Moderate abdominal pain
• 3-4 bloody stools per day
• Diffuse superficial continuous colonic inflammation proximal to the splenic flexure
• Hemoglobin of 12.0 g/dL
• ESR of 16 mm/hr

This clinical picture is consistent with moderate, extensive ulcerative colitis (UC) beyond the splenic flexure.

Treatment Algorithm for Moderate UC

First-Line Therapy

1. Oral 5-ASA (mesalamine):

   • The Toronto consensus guidelines strongly recommend oral 5-ASA preparations at dosages between 2.0 and 4.8 g/day as first-line therapy for mild to moderate active UC of any disease extent beyond proctitis 1
   • Pentasa 1000 mg four times daily provides a total daily dose of 4 g, which falls within the recommended high-dose range for moderate disease

2. Combination with rectal therapy:

   • For extensive UC, adding rectal mesalamine to oral therapy is suggested to enhance efficacy 1
   • However, in this case with disease extending proximal to the splenic flexure, oral therapy should be initiated first

Why Oral Mesalamine (Pentasa) is Preferred:

• Disease extent: For extensive UC beyond the splenic flexure, oral therapy is necessary to reach the affected areas 1
• Disease severity: For moderate symptoms, high-dose mesalamine (>3 g/day) is recommended 1
• Efficacy: High-dose mesalamine (4 g/day) has demonstrated efficacy in inducing remission in moderate UC regardless of disease extent 2
• Safety profile: Mesalamine has a favorable safety profile compared to corticosteroids and immunosuppressants

Why Other Options Are Less Appropriate:

1. Adalimumab 40 mg subcutaneously every 2 weeks:

   • Anti-TNF therapy is recommended only after failure of 5-ASA and corticosteroids 1
   • Would be premature as first-line therapy in a treatment-naïve patient with moderate UC

2. Mesalamine (Rowasa) enema 4 g rectally at bedtime:

   • Appropriate for distal disease (proctitis or left-sided colitis) but insufficient as monotherapy for extensive disease proximal to the splenic flexure 1
   • Could be added to oral therapy but not as the sole treatment

3. Budesonide 9 mg orally once daily:

   • The AGA suggests using standard-dose oral mesalamine rather than budesonide MMX for induction of remission in mild-moderate UC 1
   • Corticosteroids are recommended as second-line therapy after failure of 5-ASA therapy 1

Monitoring and Follow-up

• Evaluate for symptomatic response to oral 5-ASA induction therapy within 4-8 weeks 1
• If inadequate response occurs, consider:
  1. Adding rectal mesalamine therapy
  2. Increasing to maximum mesalamine dose if not already at 4.8 g/day
  3. Adding oral corticosteroids or budesonide MMX 1

Important Considerations

• Once-daily dosing: While the recommended regimen is 1000 mg four times daily, evidence suggests once-daily dosing may be equally effective and improve adherence 1
• Potential adverse effects: Monitor for idiosyncratic worsening of colitis, hypersensitivity reactions, and interstitial nephritis 3
• Comorbidities: For this patient with type 1 diabetes and hypertension, mesalamine is safer than corticosteroids, which can worsen glycemic control and blood pressure

By starting with high-dose oral mesalamine, we provide the most evidence-based approach to induce remission while minimizing potential adverse effects in this patient with moderate, extensive UC.