Management of Colitis
Start with combination therapy of topical mesalamine (≥1 g/day) plus oral mesalamine (≥2.4 g/day), tailored to disease extent and severity, as this represents the most effective first-line approach for newly diagnosed ulcerative colitis. 1
Initial Treatment Algorithm Based on Disease Location
Proctitis (Rectal Disease Only)
- Begin with mesalamine 1 g suppository once daily, as suppositories deliver medication more effectively to the rectum than foam or enemas and are better tolerated 1
- Add oral mesalamine ≥2.4 g/day to enhance effectiveness beyond either therapy alone 1
- Topical mesalamine is superior to topical corticosteroids for proctitis 1
Left-Sided or Extensive Colitis
- Initiate high-dose oral mesalamine at 4.8 g/day immediately rather than starting at lower doses and escalating 1, 2, 3
- Combine with topical mesalamine (enemas or suppositories) for synergistic effect 1
- This dosing strategy (4.8 g/day) has demonstrated superiority over placebo in achieving remission at 8 weeks 2
Treatment Escalation for Inadequate Response
If No Improvement Within 10-14 Days
- Continue oral mesalamine at maximum dose (4.8 g/day) for up to 40 days before declaring treatment failure 1
- Monitor closely for worsening symptoms that would necessitate earlier escalation 1
After 40 Days of Optimized Mesalamine Without Adequate Response
- Add oral prednisolone 40 mg daily 1
- Taper gradually over 6-8 weeks to prevent early relapse—avoid rapid corticosteroid reduction 1
- For moderate to severe disease, corticosteroids should be initiated earlier rather than waiting the full 40 days 4
Severe or Refractory Disease
- Consider intravenous corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) for hospitalized patients 4
- Add infliximab or vedolizumab for corticosteroid-refractory disease (no improvement within 72 hours) 5
- Hospitalization is indicated for patients with dehydration, electrolyte imbalance, or ≥7 stools per day over baseline 5
Steroid-Sparing and Maintenance Strategies
Immunomodulators
- Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.5 mg/kg/day) should be added for patients requiring repeated corticosteroid courses or those with frequent relapses 4, 6
- These agents have slow onset of action (3-6 months) and cannot be used as sole induction therapy 4
Long-Term Maintenance
- Continue lifelong maintenance therapy with mesalamine after achieving remission to prevent relapse 1, 7
- Maintenance dosing of at least 1.5-2.4 g/day is required for efficacy 7
- This may reduce colorectal cancer risk, particularly in left-sided or extensive disease 1
Critical Monitoring Requirements
Renal Function Surveillance
- Check eGFR before starting mesalamine, after 2-3 months, and then annually 1
- Mesalamine can cause interstitial nephritis, making this monitoring essential 1
Disease Activity Assessment
- Fecal calprotectin <116 mg/g may serve as a surrogate for endoscopic and histologic remission 5
- Endoscopic evaluation is highly recommended for grade ≥2 disease to stratify patients for early biologic therapy 5
Special Considerations and Common Pitfalls
Avoid These Errors
- Do not start with low-dose mesalamine (e.g., 2.4 g/day) and escalate later—begin at 4.8 g/day for optimal efficacy 3, 8
- Do not taper corticosteroids rapidly—this is strongly associated with early relapse 1
- Do not use loperamide until infection has been ruled out and only for diarrhea without colitis-related symptoms 5
When to Consider Surgery
- Failure of medical therapy including biologics 4, 6
- Development of dysplasia or colorectal cancer 9
- Life-threatening complications (toxic megacolon, perforation) 5
Immune Checkpoint Inhibitor-Related Colitis (If Applicable)
- For grade 2 immune-related colitis, hold checkpoint inhibitor and start corticosteroids at 1 mg/kg/day prednisone equivalent 5
- Consider permanently discontinuing CTLA-4 agents for grade ≥2 colitis; PD-1/PD-L1 agents may be restarted after recovery 5
- Early introduction of infliximab or vedolizumab is appropriate for high-risk endoscopic features or steroid-refractory disease 5