What is the treatment for immune-mediated colitis?

Treatment of Immune-Mediated Colitis

The treatment of immune-mediated colitis should begin with corticosteroids (1-2 mg/kg/day prednisone or equivalent) for moderate to severe cases, with early introduction of biologics such as infliximab or vedolizumab within 10 days of symptom onset for better outcomes, particularly in cases with high-risk endoscopic features or inadequate steroid response. 1, 2

Grading and Initial Assessment

Treatment approach is determined by severity of colitis:

• Grade 1 (increase of <4 bowel movements/day above baseline):

  • Continue immune checkpoint inhibitors (ICIs) with close monitoring
  • Consider loperamide or diphenoxylate/atropine for symptom control
  • Check fecal lactoferrin/calprotectin; if positive, manage as Grade 2 1

• Grade 2 (4-6 bowel movements/day above baseline, mild-moderate symptoms):

  • Hold immunotherapy
  • Start prednisone/methylprednisolone 1-2 mg/kg/day
  • Consider endoscopic evaluation to assess severity 1

• Grade 3-4 (>6 bowel movements/day, severe symptoms, life-threatening):

  • Permanently discontinue CTLA-4 inhibitors
  • Consider inpatient care
  • Administer IV methylprednisolone 1-2 mg/kg/day 1

Steroid-Refractory Management

For patients with inadequate response to steroids after 2-3 days or high-risk endoscopic features:

• Add biologic therapy early (preferably within 10 days of symptom onset):

  • Infliximab (5 mg/kg IV at weeks 0,2, and 6) OR
  • Vedolizumab (300 mg IV at weeks 0,2, and 6) 1, 2

• Vedolizumab advantages (compared to infliximab):

  • Lower recurrence rates of colitis
  • Shorter systemic steroid exposure
  • May be preferred in patients with concurrent immune-mediated hepatitis (infliximab contraindicated) 1, 3

• Infliximab advantages:

  • Requires fewer doses for remission
  • Faster onset of action 3

Refractory Cases

For patients who fail to respond to steroids plus infliximab or vedolizumab:

• Consider additional therapies:
  • Ustekinumab (IL-12/23 blocker) - 68.4% clinical remission rate in refractory cases 4
  • Fecal microbiota transplantation
  • JAK inhibitor (tofacitinib) 1

Duration of Treatment

• Corticosteroids: Continue until symptoms improve to Grade 1, then taper over 4-6 weeks
• Biologics: Consider 3 doses (weeks 0,2, and 6) to reduce risk of recurrence and increase likelihood of endoscopic/histologic remission 1
• Monitoring: Check fecal calprotectin levels to assess inflammation; low levels indicate mild inflammation or normal endoscopy 1

Important Considerations

• Early intervention is critical: Patients receiving selective immunosuppressive therapy within 10 days of colitis onset have:

  • Fewer hospitalizations
  • Less steroid taper failure
  • Shorter duration of symptoms
  • Shorter course of steroid treatment 2

• Endoscopic evaluation: Consider for Grade 2+ symptoms to assess severity and guide treatment decisions; colonic ulceration predicts need for second-line therapy 1

• Risk factors for recurrence:

  • Multiple hospitalizations
  • Steroid taper failure after biologics
  • Receiving fewer than 3 infusions of biologics
  • Higher fecal calprotectin levels after treatment 2

• Resuming immunotherapy: PD-1/PD-L1 agents associated with lower risk of flare-up compared to CTLA-4 inhibitors 1

The treatment approach should be aggressive with early introduction of biologics rather than waiting for steroid failure, as this strategy leads to better clinical outcomes and reduced morbidity in patients with immune-mediated colitis.