Treatment of Anti-SAE Induced Myositis

Initial Assessment and Management

The American College of Oncology recommends immediately discontinuing the immune checkpoint inhibitor and initiating high-dose corticosteroids at 1-2 mg/kg/day prednisone for anti-SAE induced myositis, with IVIG and/or plasma exchange added for life-threatening manifestations including dysphagia, dyspnea, or myocarditis 1, 2, 3
Assess for life-threatening features immediately, including dysphagia, dysarthria, dysphonia, dyspnea, chest pain, palpitations, or syncope, as these indicate potential myocarditis or respiratory muscle involvement 1, 2, 4
Obtain cardiac troponin I and electrocardiography for all patients with suspected myositis, as troponin I is more specific than troponin T which can be elevated from skeletal muscle alone 1, 4
Perform cardiac MRI if troponin is elevated, ECG is abnormal, or clinical suspicion for myocarditis exists, as myocarditis drives the 20% mortality rate in checkpoint inhibitor-induced myositis 4

For grade 2 (moderate weakness) myositis, discontinue checkpoint inhibitor immediately and initiate prednisone 0.5-1 mg/kg/day as first-line therapy, with referral to a rheumatologist before or concurrent with corticosteroid initiation 1, 2, 5
For grade 3-4 or life-threatening features, administer high-dose corticosteroids, such as methylprednisolone IV pulses followed by 1-2 mg/kg/day prednisone, and add IVIG and/or plasma exchange for patients with bulbar symptoms, dyspnea, myocarditis, or severe muscle weakness 1, 2, 3, 4

For corticosteroid-refractory cases, consider IL-6 receptor inhibitors, such as tocilizumab, as the preferred biologic, and TNF-α inhibitors may be considered specifically if there is associated fasciitis 1, 2, 5
Conventional DMARDs, including mycophenolate mofetil, methotrexate, or azathioprine, can be used as steroid-sparing agents 3, 4
Abatacept and alemtuzumab have shown success in glucocorticoid-refractory myocarditis and may be considered as rescue therapy given the high mortality rate when myositis is complicated by myocarditis or severe respiratory failure 3, 4

Monitor CK levels, ESR, and CRP regularly to assess treatment response, and perform muscle strength examination at each follow-up visit 5, 6, 7
Continue cardiac monitoring as myocarditis can develop or worsen even with treatment 1, 4
Once improvement is achieved, taper corticosteroids progressively to the lowest effective dose, with a target maintenance dose of ≤10 mg/day prednisone equivalent when possible 1, 2, 8

Do not delay treatment while awaiting biopsy confirmation, as over 80% of patients achieve favorable outcomes with prompt ICI discontinuation and immunomodulatory treatment 1, 2
Do not miss concurrent myasthenia gravis, which occurs in 12.5% of checkpoint inhibitor myositis cases and can contribute to bulbar and respiratory symptoms 3, 4
Do not use troponin T alone for cardiac assessment, as it is expressed by regenerating skeletal muscle; troponin I is myocardium-specific 1
Do not rechallenge with checkpoint inhibitors, as caution is strongly advised given the potentially fatal nature of recurrent myositis 6