What is the treatment for colitis?

Treatment of Colitis

Treatment of colitis depends critically on disease severity and extent, with mild disease managed with 5-aminosalicylates (5-ASA), moderate-to-severe disease requiring corticosteroids combined with 5-ASA, and acute severe colitis demanding intravenous corticosteroids with early consideration of rescue therapy (infliximab or cyclosporine) or surgery within 3-7 days if refractory. 1

Initial Assessment and Classification

Before initiating treatment, classify disease severity using objective criteria:

• Severe colitis is defined by bloody stool frequency ≥6/day plus at least one of: tachycardia >90/min, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h (CRP >30 mg/L can substitute) 2
• Obtain stool cultures (including C. difficile, parasites, CMV), CBC, CMP, and inflammatory markers (fecal calprotectin, lactoferrin) to exclude infection and confirm active inflammation 1
• Consider flexible sigmoidoscopy with biopsy to confirm diagnosis and assess disease extent, particularly to identify ulceration which predicts steroid-refractory disease requiring early biologic therapy 1

Treatment Algorithm by Disease Location and Severity

Proctitis (Rectal Disease Only)

First-line: Mesalazine 1g suppository once daily 2

• If no response or intolerance: add oral mesalazine 2-4g daily OR substitute topical corticosteroids 1
• For refractory proctitis: consider oral corticosteroids, topical tacrolimus, JAK inhibitors, or biologic therapy 1

Mild to Moderate Left-Sided or Extensive Colitis

First-line: Oral mesalazine 2-4g daily combined with topical mesalazine 1g daily 1, 2

• Combination therapy is superior to either agent alone 1
• If no response within 2-4 weeks: initiate oral prednisolone 40mg daily 1
• Taper prednisolone gradually over 8 weeks according to clinical response 1, 3

Moderate to Severe Colitis

First-line: Oral prednisolone 40-60mg daily combined with mesalazine 1, 4, 3

• Single daily dosing is as effective as split-dosing and causes less adrenal suppression 3
• Monitor for clinical response within 2 weeks 4
• If inadequate response to oral corticosteroids within 2 weeks, corticosteroid taper is unsuccessful, or repeated courses are needed: escalate to advanced therapy (biologics such as infliximab or adalimumab, vedolizumab, JAK inhibitors, or S1P agonists) 1
• Critical pitfall: Approximately 50% of patients experience corticosteroid-related adverse events including acne, edema, sleep disturbance, mood changes, glucose intolerance, and dyspepsia 3

Acute Severe Colitis (Hospitalized Patients)

This is a medical emergency requiring joint gastroenterology-surgical management 1, 2

Immediate interventions:

• Intravenous methylprednisolone 40-60mg/24h or hydrocortisone 100mg four times daily 1
• Higher doses provide no additional benefit; lower doses are less effective 1
• IV fluid and electrolyte replacement with potassium supplementation ≥60 mmol/day (hypokalaemia promotes toxic dilatation) 1
• Subcutaneous low-molecular-weight heparin for thromboprophylaxis 1, 2
• Blood transfusion to maintain hemoglobin >8-10 g/dL 1
• Nutritional support (enteral preferred over parenteral) if malnourished 1, 2
• Unprepared flexible sigmoidoscopy with biopsy to exclude CMV infection 1
• Withdraw anticholinergics, antidiarrheals, NSAIDs, and opioids (risk of toxic dilatation) 1

Monitoring requirements:

• Physical examination daily for abdominal tenderness and rebound 1
• Vital signs four times daily 1
• Stool chart documenting frequency, character, and blood 1
• CBC, CRP/ESR, electrolytes, albumin every 24-48 hours 1
• Plain abdominal radiograph if colonic dilatation suspected (transverse colon >5.5 cm) 1

Rescue therapy decision point (3-5 days):

If no improvement or deterioration within 3-5 days of IV corticosteroids, initiate rescue therapy 1, 2:

• Infliximab: 5mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance 5
  • Combination with azathioprine achieves corticosteroid-free remission in 39.7% vs 22.1% with infliximab alone 4
  • Can be used as monotherapy in patients who should avoid steroids (steroid psychosis, osteoporosis, poorly controlled diabetes) 1

OR

• Cyclosporine: 2mg/kg/day IV (as effective as IV methylprednisolone for acute severe UC) 1
  • Transition to oral cyclosporine with azathioprine/6-mercaptopurine for responders 1

Surgical indications (do not delay):

• Failure to improve or deterioration within 48-72 hours of rescue therapy 2
• Free perforation, life-threatening hemorrhage, or generalized peritonitis 2
• Toxic megacolon with perforation, massive bleeding, clinical deterioration, or shock 2
• Critical pitfall: Prolonged observation increases risk of perforation with very high mortality; subtotal colectomy with ileostomy is the preferred emergency surgical approach 2, 6

Maintenance Therapy

Lifelong maintenance is recommended for all patients, particularly those with left-sided or extensive disease 1, 2

• Continue the agent successful in achieving induction, except corticosteroids which must never be used for long-term maintenance 1, 4, 3
• Options include: mesalazine 2-4g daily, azathioprine/6-mercaptopurine (with therapeutic drug monitoring of 6-TGN levels), or continuation of biologic therapy 1, 7
• For patients on infliximab: continue 5mg/kg every 8 weeks; consider adding azathioprine for improved outcomes 4, 5
• Patients requiring ≥2 corticosteroid courses in the past year or who become corticosteroid-dependent require treatment escalation to thiopurines, anti-TNF therapy, vedolizumab, or tofacitinib 3

Treatment Goals and Monitoring

The treatment goal has shifted from clinical response to achieving biochemical, endoscopic, and histological remission 1, 2

• Mucosal healing on endoscopy and/or fecal calprotectin ≤116 mg/g should guide decisions on stopping biologic treatment and resuming therapy 1
• For patients on biologics: therapeutic drug monitoring can optimize outcomes in primary nonresponse and secondary loss of response 7

Special Considerations

Immune Checkpoint Inhibitor-Associated Colitis

For grade 1 (increase of <4 stools/day): continue checkpoint inhibitor with conservative management and close monitoring 1

For grade ≥2: consider permanently discontinuing CTLA-4 agents; may restart PD-1/PD-L1 agents if recovery to grade ≤1 with concurrent immunosuppressant maintenance if clinically indicated 1

Infection Screening

• Test for C. difficile in all patients (more prevalent in severe UC, associated with increased morbidity/mortality); treat with oral vancomycin if detected 1
• Screen for latent tuberculosis, hepatitis B, and HIV before initiating biologic therapy 1, 5
• Annual screening for patients requiring biologics >1 year 1