What is the initial management for checkpoint inhibitor (CI) colitis?

Initial Management of Checkpoint Inhibitor Colitis

For patients with suspected checkpoint inhibitor colitis, the initial management should include ruling out infectious causes of diarrhea, followed by corticosteroid therapy for moderate to severe cases (grade ≥2), with early consideration of endoscopic evaluation to guide treatment decisions. 1

Assessment and Diagnosis

Initial Workup

• Laboratory tests: CBC, CMP, TSH
• Stool studies: Culture, C. difficile testing, parasites, CMV, viral etiologies
• Inflammatory markers: Fecal lactoferrin and calprotectin (helps stratify patients for urgent endoscopy)
• Imaging: CT scan of abdomen/pelvis for patients with abdominal pain, bleeding, or fever to rule out complications like perforation or abscess 1

Endoscopic Evaluation

• Recommended for grade ≥2 colitis to:
  • Confirm diagnosis
  • Assess severity
  • Identify ulcerations (predicts steroid-refractory course)
  • Guide treatment decisions 1

Treatment Algorithm by Severity

Grade 1 (< 4 stools/day over baseline)

• Continue immune checkpoint inhibitor (ICI) therapy
• Supportive care with loperamide after ruling out infection
• Monitor for dehydration and recommend dietary changes
• Close monitoring every 3 days until stabilized
• Consider gastroenterology consult for prolonged cases 1

Grade 2 (4-6 stools/day over baseline)

1. Hold ICI therapy until recovery to grade 1
2. Administer corticosteroids: prednisone 1 mg/kg/day until symptoms improve to grade 1
3. Taper steroids over 4-6 weeks
4. Consider gastroenterology consultation
5. Endoscopic evaluation is highly recommended 1

Grade 3-4 (≥7 stools/day, hospitalization indicated)

1. Hold ICI therapy (consider permanent discontinuation of CTLA-4 agents)
2. Administer corticosteroids: prednisone/methylprednisolone 1-2 mg/kg/day
3. Consider hospitalization for dehydration or electrolyte imbalance
4. Consider early introduction of biologics for high-risk endoscopic features or inadequate steroid response within 72 hours 1

Management of Steroid-Refractory Cases

Approximately one-third of patients have inadequate response to first-line corticosteroid treatment 1, 2. Consider second-line therapy if:

• No response to high-dose steroids within 72 hours
• No complete response within one week
• Recurrent symptoms during steroid taper 1

Second-Line Options

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

Both appear highly effective with responses typically occurring within one week, which is faster than in traditional IBD 2.

Special Considerations

Microscopic Colitis

• Patients with microscopic colitis (inflammation without visible mucosal changes) may respond to budesonide rather than systemic steroids 3, 4

CMV Reactivation

• Consider testing for CMV reactivation in steroid-refractory cases, as this can complicate management 5

Resuming ICI Therapy

• May consider resuming PD-1/PD-L1 agents (lower risk of flare) after symptoms improve to grade ≤1
• CTLA-4 inhibitors have higher risk of recurrence
• Consider endoscopic and histologic remission before resuming therapy 1

Pitfalls to Avoid

1. Delaying treatment: Rapid progression of ICI colitis can occur within days, particularly with ipilimumab 1
2. Missing infections: Always rule out infectious causes before starting immunosuppression 1
3. Overlooking ulcerations: Colonic ulceration predicts steroid-refractory course and need for second-line therapy 1
4. Inadequate monitoring: Patients with grade ≥2 colitis require close monitoring for response to therapy

By following this structured approach to the initial management of checkpoint inhibitor colitis, clinicians can effectively control symptoms, minimize complications, and potentially allow patients to continue their cancer therapy when appropriate.