Immune-related adverse events: management by organ and grade

Gastrointestinal

Colitis and diarrhoea

Diarrhoea in about 10-15% on anti-PD-1 alone and 30-40% with ipilimumab combinations; grade 3-4 colitis about 1-2% versus 10%.

Card fits one page

Work-up: Stool culture, C. difficile, faecal calprotectin; CT if severe; early flexible sigmoidoscopy or colonoscopy for grade 2 or above (ulceration predicts steroid refractoriness). Rule out CMV before infliximab.

Grade	Checkpoint inhibitor	Steroids	If refractory / other measures	Rechallenge
Grade 1 Fewer than 4 stools a day over baseline	Continue	None	Loperamide, hydration, dietary advice; monitor for progression.	Not applicable: treatment continues.
Grade 2 4-6 stools a day over baseline, or abdominal pain, mucus or blood	Hold	Prednisone 1 mg/kg/day (or equivalent) if symptoms persist 2-3 days; taper over 4-6 weeks	If no response in 2-3 days, treat as grade 3 (infliximab or vedolizumab). ASCO: consider permanently discontinuing CTLA-4 antibodies; PD-1 may be resumed.	Resume once grade 1 or better and prednisone at 10 mg/day or less.
Grade 3 7 or more stools a day, incontinence, hospitalisation indicated	Hold; consider permanent stop	IV methylprednisolone 1-2 mg/kg/day	Infliximab 5 mg/kg (or vedolizumab) if no improvement within 48-72 hours; repeat dose at 2 weeks if needed. Steroid taper over 4-6 weeks. Early infliximab or vedolizumab (within 10 days) shortens steroid exposure without loss of tumour control in retrospective series.	ASCO and ESMO: consider resuming anti-PD-1 after recovery; permanently discontinue CTLA-4 antibodies. NCCN: consider resuming anti-PD-(L)1 after resolution.
Grade 4 Life-threatening: perforation, ischaemia, toxic megacolon	Permanently discontinue	IV methylprednisolone 1-2 mg/kg/day	Infliximab or vedolizumab within 48-72 hours if not improving; surgical review for perforation.	Permanently discontinue.

Where the guidelines differ: ESMO and NCCN allow biologics (infliximab, vedolizumab) earlier, at grade 2 not responding within 3 days; ASCO places them after 48-72 hours of high-dose steroids at grade 3.

Sources: ASCO 2021 guideline update (Schneider et al., JCO); NCCN Management of Immunotherapy-Related Toxicities; ESMO 2022 Clinical Practice Guideline (Haanen et al., Ann Oncol)

Products: Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Cemiplimab, Avelumab, Dostarlimab, Ipilimumab, Tremelimumab, Relatlimab + nivolumab, Tislelizumab, Toripalimab. Compare toxicity rates →

Steroid tapers are over at least 4-6 weeks; give PJP prophylaxis above 20 mg prednisone-equivalent for over 4 weeks, gastric protection and bone protection; screen for HBV and TB before infliximab. General rule across guidelines: grade 2 hold and resume at grade 1 on 10 mg/day or less; grade 4 permanently discontinue except endocrinopathies controlled by replacement. Not medical advice. Sources: ASCO 2021 guideline update, NCCN Management of Immunotherapy-Related Toxicities, ESMO 2022 Clinical Practice Guideline.

Principles shared by all three guidelines

Grade 1: usually continue with monitoring (except pneumonitis, myocarditis and neurological events, where even grade 1 means hold).

Grade 2: hold; prednisone 0.5-1 mg/kg if not settling; resume at grade 1 on 10 mg/day or less.

Grade 3: hold or stop; IV methylprednisolone 1-2 mg/kg; add a second agent (infliximab, vedolizumab, mycophenolate, IVIG, tocilizumab) if no response in 48-72 hours.

Grade 4: permanently discontinue, except endocrinopathies controlled by hormone replacement.

Myocarditis of any grade, and grade 2 or above myasthenia or Guillain-Barré, mean permanent discontinuation; pulse-dose steroids for myocarditis.

Read with

The toxicity compare table holds the label rates for each checkpoint inhibitor; the interaction checker notes that steroids given for irAEs do not appear to blunt efficacy; and each product page carries its safety tab. Time to onset matters: colitis and hepatitis are commonest at 6-12 weeks, endocrine events at 8-20 weeks, but any event can occur months after the last dose.