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Immune-related Adverse Events from Immune Checkpoint Inhibitor Therapy

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38 Treatment Table 5. Musculoskeletal Toxicities G2: Moderate pain associated with signs of inflammation, erythema, or joint swelling ; limiting instrumental ADL. • Consider holding ICPi. • Escalate analgesia and consider higher doses of NSAIDS as needed. • If inadequately controlled, initiate prednisone 10–20 mg/day or equivalent. • If improvement, slow taper according to response during the next 4–6 weeks. If no improvement after initial 4 weeks treat as G3. • If unable to lower corticosteroid dose to below 10 mg/d after 6–8 weeks, consider DMARD. • Consider intra-articular steroid injections for large joints. • Referral to rheumatolog y. G3–4: Severe pain associated with signs of inflammation, erythema, or joint swelling ; irreversible joint damage; disabling ; limiting self-care ADL. • Hold ICPi temporarily and may resume in consultation with rheumatolog y, if recover to ≤G1. • Initiate oral prednisone 0.5–1 mg/kg. • If failure of improvement after 2 weeks or worsening in meantime, consider synthetic or biologic DMARD. ▶ Synthetic: methotrexate, leflunomide, hydroxychloroquine, sulfasalazine alone or in combination. ▶ Biologic: Consider anti-cytokine therapy such as tumor necrosis factor (TNF) -α or IL-6 antagonists. Note: As caution, IL6 inhibition can cause intestinal perforation. While this is extremely rare, it should not be used in patients with concomitant immune-related colitis. • Referral to rheumatolog y. Additional considerations: • Early recognition is critical to avoid erosive joint damage. • Corticosteroids can be used as part of initial therapy in IA, but due to likely prolonged treatment requirements, physicians should consider starting steroid- sparing agents earlier than one would with other irAEs. • Oligoarthritis can be treated early on with intra-articular steroids, consider early referral. (cont'd)

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