1. Infectious causes of diarrhea should be excluded before treatment of suspected immune checkpoint inhibitors (ICI) colitis.
2. Early stool testing for inflammatory markers (lactoferrin and calprotectin) in patients with grade 2 or higher colitis/diarrhea (more than four bowel movements daily above baseline) according to the Common Terminology Criteria for Adverse Events, Version 5 (CTCAE) and selected patients with less-severe diarrhea may help stratify high-risk patients for endoscopic evaluation.
3. Endoscopic confirmation of the diagnosis and severity of ICI colitis should be considered before initiation of high-dose systemic glucocorticoids.
4. Abdominal imaging may be considered to exclude serious complications in patients with dominant symptoms of pain, fever, or bleeding, but should not be performed routinely in patients with diarrhea alone.
5. Rapid progression of ICI colitis may occur within a period of days, particularly in patients treated with ipilimumab and, therefore, prompt diagnosis and treatment is required.
6. ICI colitis typically responds to high-dose systemic glucocorticoids, given in doses of 0.5-2 mg/kg prednisone equivalent daily with a taper of 4-6 weeks; however, these doses and schedules have not been rigorously examined. Infliximab and vedolizumab are reasonable options for treatment of glucocorticoid refractory colitis.
7. Budesonide is ineffective as prophylactic treatment for ICI colitis, but may be used for treatment of ICI-associated microscopic colitis.
8. Patients who develop ICI colitis may be retreated with immunotherapy under select conditions.
9. Patients with inflammatory bowel disease may have an increased risk of ICI-associated gastrointestinal adverse events, but may derive cancer treatment benefit from checkpoint blockade.
10. All patients undergoing ICI therapy should undergo baseline evaluation of liver chemistries (total bilirubin, alkaline phosphatase, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]), as well as pretreatment screening for hepatitis B virus serologies (hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody). Liver chemistries should be repeated before each ICI treatment cycle, with management based on CTCAE grade.
11. For patients with CTCAE grade 1 hepatitis (AST/ALT 1-3× the upper limit of normal [ULN] or total bilirubin 1-1.5× ULN), liver monitoring should be repeated 1-2 times weekly. For patients with CTCAE grade 2 hepatitis (AST/ALT >3-5× ULN or total bilirubin >1.5-3× ULN), ICI therapy should be held until resolution to grade 1; for patients with clinical symptoms of liver toxicity, prednisone 0.5-1.0 mg/kg/d or equivalent may be administered.
12. For patients with grade 3 hepatitis (AST/ALT >5-20× ULN or total bilirubin >3-10× ULN), ICI should be discontinued, urgent gastrointestinal/liver consultation is advised, and glucocorticoids should be initiated at a dose of 1-2 mg/kg methylprednisolone or equivalent. Second-line immunomodulators, such as azathioprine or mycophenolate mofetil, may be considered in patients who fail to demonstrate improvement in clinical hepatitis within 3-5 days.
13. For patients with CTCAE grade 4 hepatitis (AST/ALT >20× ULN or total bilirubin >10× ULN or hepatic decompensation, such as ascites or encephalopathy) hospitalization is appropriate, preferably at a referral center with expertise in the care of patients with liver failure. ICI should be permanently discontinued, and patients started on 2 mg/kg/d methylprednisolone or equivalent.
14. All patients who develop elevated liver chemistries on ICI therapy should undergo diagnostic evaluation for alternate etiologies of liver injury, including consideration of a liver biopsy.
15. Patients who develop elevated alkaline phosphatase and/or bilirubin on ICI therapy should undergo biliary imaging to assess for biliary obstruction with hepatic ultrasound, magnetic resonance cholangiopancreatography, or endoscopic ultrasound.
