What is the treatment for anti-SAE (Specific Antigen) induced myositis?

Treatment of Anti-SAE Induced Myositis

For anti-SAE induced myositis, immediately discontinue the immune checkpoint inhibitor and initiate high-dose corticosteroids at 1-2 mg/kg/day prednisone (or IV methylprednisolone pulses for severe cases), with IVIG and/or plasma exchange added for life-threatening manifestations including dysphagia, dyspnea, or myocarditis. 1

Initial Assessment and Risk Stratification

Critical Evaluation Required

• Assess for life-threatening features immediately: dysphagia, dysarthria, dysphonia (bulbar symptoms), dyspnea, chest pain, palpitations, or syncope, as these indicate potential myocarditis or respiratory muscle involvement 1
• Obtain cardiac troponin I (more specific than troponin T which can be elevated from skeletal muscle alone) and electrocardiography for all patients with suspected myositis 1
• 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 1
• Measure CK levels (often markedly elevated), along with inflammatory markers (ESR, CRP), and consider myositis-associated autoantibodies, though these are frequently negative in checkpoint inhibitor-induced cases 1
• Order MRI and EMG to confirm diagnosis and assess extent of muscle involvement; fasciitis is frequently reported on MRI 1

Clinical Context for Anti-SAE Myositis

• Anti-SAE antibodies are specifically associated with high prevalence of dysphagia and cutaneous manifestations that precede myopathy development, making bulbar symptom assessment particularly critical 2
• The median time to myositis onset with checkpoint inhibitors is 4 weeks, earlier than most other immune-related adverse events 1

Treatment Algorithm by Severity

Grade 2 (Moderate Weakness)

• Discontinue checkpoint inhibitor immediately - this is mandatory even for grade 2 symptoms 1
• Initiate prednisone 0.5-1 mg/kg/day as first-line therapy 1
• Refer to rheumatologist before or concurrent with corticosteroid initiation 1
• Improvement is often noted within days after checkpoint inhibitor discontinuation in moderate cases 1

Grade 3-4 or Life-Threatening Features

• Administer high-dose corticosteroids: methylprednisolone IV pulses followed by 1-2 mg/kg/day prednisone 1
• Add IVIG (used in up to 20% of reported cases) and/or plasma exchange (used in approximately 10% of cases) for patients with bulbar symptoms, dyspnea, myocarditis, or severe muscle weakness 1
• Approximately 40% of patients require these additional treatment options beyond corticosteroids alone 1
• Consider hospitalization for severe weakness or respiratory compromise 1

Refractory Disease Management

Second-Line Immunosuppression

• IL-6 receptor inhibitors (tocilizumab) should be considered as the preferred biologic for corticosteroid-refractory cases 1
• TNF-α inhibitors may be considered specifically if there is associated fasciitis 1
• Conventional DMARDs including mycophenolate mofetil, methotrexate, or azathioprine can be used as steroid-sparing agents 1

Rescue Therapy for Severe Refractory Cases

• Abatacept has shown success in glucocorticoid-refractory myocarditis after plasma exchange failure 1
• Alemtuzumab (T-cell directed therapy) has been successfully used in refractory myocarditis 1
• These agents warrant consideration as rescue therapy given the high mortality rate when myositis is complicated by myocarditis or severe respiratory failure 1

Monitoring and Tapering Strategy

Ongoing Assessment

• Monitor CK levels, ESR, and CRP regularly to assess treatment response 1
• Perform muscle strength examination at each follow-up visit 3
• Continue cardiac monitoring as myocarditis can develop or worsen even with treatment 1

Corticosteroid Tapering

• Once improvement is achieved, taper corticosteroids progressively to the lowest effective dose 1
• The target maintenance dose should be ≤10 mg/day prednisone equivalent when possible, though this may be higher than for idiopathic inflammatory myopathies due to concerns about tumor response 1
• Taper should occur over weeks as clinical response permits 1

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting biopsy confirmation - over 80% of patients achieve favorable outcomes with prompt ICI discontinuation and immunomodulatory treatment 1
• Do not miss concurrent myasthenia gravis, which occurs in 12.5% of checkpoint inhibitor myositis cases and can contribute to bulbar and respiratory symptoms 1
• 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 - caution is strongly advised given the potentially fatal nature of recurrent myositis 1
• Do not assume normal cardiac enzymes rule out myocarditis - clinical syndrome and ECG changes may still warrant cardiac MRI 1