When are corticosteroids (steroids) used to treat severe immunotherapy-related adverse events, such as colitis, pneumonitis, or hepatitis?

When to Use Corticosteroids for Immunotherapy Side Effects

Corticosteroids are the first-line treatment for grade ≥2 immune-related adverse events (irAEs) affecting most organ systems, with dosing and route determined by toxicity grade and specific organ involvement. 1

Grade-Based Steroid Initiation Algorithm

Grade 1 (Mild) Toxicities

• Most grade 1 irAEs do not require steroids and can be managed with supportive care and continued immunotherapy monitoring 1
• Exception: Grade 1-2 pneumonitis requires prednisone 1-2 mg/kg orally after ruling out infection, even at lower grades due to potential severity 1

Grade 2 (Moderate) Toxicities

Colitis/Diarrhea:

• Start corticosteroids at 1 mg/kg/day prednisone unless diarrhea is transient 1
• Hold immunotherapy until recovery to grade ≤1 1
• Consider budesonide for localized disease 1

Hepatitis:

• Withhold immunotherapy and monitor closely 1
• If no improvement after 1 week, start (methyl)prednisone 0.5-1 mg/kg 1

Pneumonitis:

• Interrupt immunotherapy immediately 1
• Start prednisone 1-2 mg/kg orally after attempting to rule out infection 1

Endocrinopathies:

• Thyroiditis with inflammation: prednisone 1 mg/kg orally 1
• Hypophysitis with neurological symptoms: (methyl)prednisone 1 mg/kg orally, taper over 2-4 weeks 1

Grade 3 (Severe) Toxicities

Colitis:

• Discontinue immunotherapy (especially CTLA-4 agents) 1
• Start 1-2 mg/kg/day prednisone or IV methylprednisolone if concern for upper GI involvement 1
• Consider hospitalization for dehydration/electrolyte imbalance 1
• Add infliximab or vedolizumab early if high-risk endoscopic features or no improvement within 3 days 1

Hepatitis:

• Permanently discontinue immunotherapy 1
• Start (methyl)prednisone 1-2 mg/kg immediately 1
• If no improvement in 2-3 days, add mycophenolate mofetil 1000 mg three times daily 1
• Taper over 4-6 weeks with close monitoring 1

Pneumonitis:

• Permanently discontinue immunotherapy 1
• Admit to hospital (ICU if necessary) 1
• Start high-dose (methyl)prednisone 2-4 mg/kg IV immediately 1
• Add infliximab, mycophenolate mofetil, or cyclophosphamide if deterioration occurs 1

Neurological Toxicity:

• Admit patient for severe symptoms 1
• Start (methyl)prednisone 1-2 mg/kg orally or IV 1
• Consider plasmapheresis or IVIG for Guillain-Barré or myasthenia-like symptoms 1

Grade 4 (Life-Threatening) Toxicities

All Grade 4 irAEs:

• Permanently discontinue immunotherapy 1
• Immediate hospitalization required 1
• Start 2-4 mg/kg/day methylprednisolone IV depending on organ system 1

Hepatitis Grade 4:

• (Methyl)prednisone 2 mg/kg IV 1
• Add mycophenolate mofetil if no improvement within 2-3 days 1
• Consult hepatologist; consider ATG or tacrolimus for refractory cases 1

Colitis Grade 4:

• Methylprednisolone 1-2 mg/kg/day IV 1
• Early biologics (infliximab or vedolizumab) if inadequate response after 3 days 1

Pneumonitis Grade 4:

• (Methyl)prednisone 2-4 mg/kg IV 1
• Taper over 4-6 weeks minimum 1

Special Considerations for Cardiac Toxicity

Myocarditis (any grade when suspected):

• Admit immediately and start high-dose (methyl)prednisone 1-2 mg/kg 1
• This is an exception where steroids are started urgently regardless of grade due to high mortality risk 1
• Consider adding mycophenolate mofetil or tacrolimus if deterioration occurs 1

Critical Steroid Tapering Principles

• Taper over 4-6 weeks minimum for most irAEs once symptoms improve to grade ≤1 1
• Longer tapers (6+ weeks) required for pneumonitis due to high relapse rates 1
• Do not resume immunotherapy until steroid dose ≤10 mg prednisone daily 1
• Rapid tapers increase infection risk and irAE recurrence 1

When Steroids Are NOT Recommended

• Type 1 diabetes mellitus (grade 3-4): Role of corticosteroids in preventing complete loss of insulin-producing cells is unknown and not recommended 1
• Grade 1 diarrhea without colitis: Continue immunotherapy with loperamide only 1
• Asymptomatic pancreatic enzyme elevations: Routine steroids not indicated 1

Steroid-Refractory Disease Management

If no improvement within 2-3 days on appropriate steroid dosing: 2

• Hepatitis: Add mycophenolate mofetil as first-line 1, 2
• Colitis: Add infliximab 5 mg/kg, then vedolizumab if refractory 1, 2
• Pneumonitis: Add mycophenolate mofetil or IVIG; data on infliximab are conflicting 2, 3
• Myocarditis: Add abatacept, ATG (with or without mycophenolate mofetil), or ruxolitinib with abatacept 2

Common Pitfalls to Avoid

• Do not delay steroids for grade ≥2 pneumonitis or any grade myocarditis while awaiting diagnostic workup—mortality risk is too high 1
• Avoid oral prednisone when bowel edema is present—use IV methylprednisolone instead due to impaired GI absorption 4
• Do not use infliximab for hepatic irAEs—it is contraindicated and can worsen liver toxicity 1
• Prolonged steroid use (>30 days) without adding steroid-sparing agents increases infection risk significantly 1
• Do not restart CTLA-4 inhibitors after grade ≥3 colitis—recurrence risk is unacceptably high 1