What is the recommended treatment for a new case of Ulcerative Colitis (UC) in a 48-year-old?

Treatment of New-Onset Ulcerative Colitis in a 48-Year-Old

For a newly diagnosed 48-year-old with ulcerative colitis, start with oral mesalamine 2.4-4.8 g/day combined with rectal mesalamine 1 g daily if disease extends beyond the rectum, or mesalamine suppositories 1 g daily for isolated proctitis. 1

Initial Disease Assessment

Before initiating therapy, you must determine three critical factors that dictate treatment selection:

• Disease extent: Proctitis (rectum only), left-sided (up to splenic flexure), or extensive (beyond splenic flexure) 1
• Disease severity: Mild (≤4 stools/day, minimal blood), moderate (4-6 stools/day with blood), or severe (≥6 bloody stools/day plus systemic signs like tachycardia >90, fever >37.8°C, hemoglobin <10.5 g/dL, or ESR >30) 1, 2
• Baseline labs and stool studies: Complete blood count, CRP, albumin, stool culture, and Clostridioides difficile testing 1

First-Line Treatment Algorithm by Disease Location

For Proctitis (Rectum Only)

Use mesalamine 1 g suppositories once daily as monotherapy. 1 This is superior to oral mesalamine for isolated rectal disease, with response rates of 40-70% and remission rates of 15-20%. 3 Patients who prioritize convenience over maximal efficacy may choose oral mesalamine instead, though this is less effective. 1

For Left-Sided or Extensive Disease (Mild-Moderate Severity)

Combine oral mesalamine 2.4-4.8 g/day with rectal mesalamine 1 g enemas daily. 1 The combination approach is more effective than oral therapy alone for inducing complete remission. 1

• Standard dosing is 2-3 g/day, but higher doses (>3 g/day up to 4.8 g/day) show superior efficacy in moderate disease without increased toxicity 1, 3
• Once-daily dosing is as effective as divided dosing and improves adherence 1
• Rectal mesalamine enemas are superior to rectal corticosteroids for left-sided disease 1

For Moderate-to-Severe Disease at Presentation

Initiate oral prednisone 40 mg daily as bridge therapy while simultaneously starting a biologic agent (infliximab, adalimumab, vedolizumab, or ustekinumab) for long-term disease control. 1, 4 The 2025 British Society of Gastroenterology guidelines emphasize early advanced therapy rather than step-up approaches in moderate-severe disease to prevent complications and colectomy. 1, 4

Critical Timeframe for Assessment

Evaluate response to 5-ASA therapy at 4-8 weeks. 1 If no symptomatic improvement occurs by this point, this constitutes 5-ASA failure and requires escalation. Do not continue ineffective 5-ASA therapy beyond 8 weeks, as this delays proven effective treatments and risks disease progression. 1

Maintenance Therapy After Remission Induction

Continue the same agent that successfully induced remission at the same dose. 1 For 5-ASA-induced remission, maintain at least 2 g/day indefinitely. 1 Higher maintenance doses (2.4 g/day vs 1.2 g/day) prolong remission, particularly in extensive disease. 1

All patients with UC should receive lifelong maintenance therapy, especially those with left-sided or extensive disease, as this reduces relapse rates and may decrease colorectal cancer risk. 1

When to Escalate Beyond 5-ASA

Do not switch between different oral 5-ASA formulations if one fails—this is ineffective. 1 Instead, escalate to:

• Oral corticosteroids (prednisone 40 mg daily) for 5-ASA-refractory mild-moderate disease as bridge therapy 1
• Biologic agents (anti-TNF, anti-integrin, or anti-IL12/23) or JAK inhibitors for moderate-severe disease or corticosteroid-dependent disease 1, 4, 5

Common Pitfalls to Avoid

• Do not use corticosteroids for maintenance therapy—they are for induction only and should be tapered after 7-10 days maximum 2
• Do not delay biologic therapy in moderate-severe disease—step-up approaches increase hospitalization and colectomy risk 4
• Do not use probiotics, curcumin, or fecal microbiota transplant—these lack evidence and delay proven therapies 1
• Do not underdose mesalamine—efficacy is dose-dependent, with 4.8 g/day optimal for active disease 1, 3

Special Considerations for This 48-Year-Old Patient

At age 48, this patient falls within the second incidence peak (50-80 years). 6 Ensure baseline tuberculosis screening before any biologic therapy, as TNF inhibitors carry infection risks. 7 If considering thiopurines or anti-TNF combination therapy, counsel about hepatosplenic T-cell lymphoma risk, though this is primarily seen in young males. 7

The patient should understand that despite optimal medical therapy, approximately 20% of UC patients require hospitalization and 7% undergo colectomy within 5 years of diagnosis. 5 Life expectancy is reduced by approximately 5 years compared to the general population. 5