Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1. Their immune-related adverse effects (irAEs) — colitis, thyroiditis, pneumonitis, hepatitis — are best managed with:

• A Anti-TNF agents (infliximab) as first-line for all irAEs regardless of organ involved
• B High-dose systemic corticosteroids, which suppress the over-activated immune response; permanent drug discontinuation for grade 3–4 toxicity ✓
• C Antihistamines and dose reduction; corticosteroids are avoided as they impair antitumour immunity
• D IL-6 receptor antagonists (tocilizumab) as standard first-line treatment for all irAEs

Explanation

IrAEs result from generalised immune activation — the same mechanism that produces antitumour effects. High-dose corticosteroids (prednisone 1–2 mg/kg/day) are the mainstay of treatment, effectively suppressing the overactivated T-cell response. For steroid-refractory colitis and hepatitis, infliximab (anti-TNF) is added. For grade 3–4 irAEs, checkpoint inhibitor therapy is permanently discontinued. Evidence suggests that immunosuppression for irAE management does not significantly impair the pre-existing antitumour immune response.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.