Autoimmune inflammation of any organ, ending in -itis
Expansion
Mechanism: checkpoint inhibitors (anti-PD-1 nivolumab, pembrolizumab; anti-PD-L1; anti-CTLA-4 ipilimumab) release the brakes on T cells. The same mechanism that attacks the tumour can attack any normal tissue.
Almost every event ends in -itis
- Colitis: diarrhoea, the commonest serious event. Risk of perforation
- Hepatitis
- Pneumonitis
- Thyroiditis, causing thyrotoxicosis then hypothyroidism
- Hypophysitis, causing hypopituitarism and adrenal insufficiency
- Dermatitis, rash and pruritus, the commonest overall
- Nephritis, myocarditis, arthritis, neuropathy, type 1 diabetes
“Anything new in a patient on immunotherapy is immune related until proven otherwise.”
Timing: skin at 2 to 3 weeks, gut and liver at 6 to 7, endocrine later. But events can occur at any time, including months after stopping.
Treatment is grade dependent: withhold the drug and give corticosteroids for moderate or severe events, escalating to infliximab or mycophenolate if steroid refractory.
The critical exception is endocrine: hypophysitis and adrenal insufficiency are treated with hormone replacement, and the patient may need lifelong hydrocortisone. Steroid replacement must not be delayed while investigating.
Combination anti-CTLA-4 with anti-PD-1 markedly increases the frequency and severity.