What is the treatment for necrotizing myopathy?

Treatment for Necrotizing Myopathy

The treatment of immune-mediated necrotizing myopathy (IMNM) requires aggressive immunosuppressive therapy with multiple agents, as corticosteroid monotherapy is typically insufficient to control the disease. 1

Classification and Diagnosis

Necrotizing myopathy is characterized by:

• Necrotic muscle fibers with minimal or no inflammatory infiltrate on muscle biopsy
• Proximal muscle weakness (predominantly in lower extremities in 73% of cases)
• Elevated creatine kinase (CK) levels (median 5326 U/L)
• Possible distal weakness (41%), dysphagia (35%), and dyspnea (37%)

Two main categories:

1. Immune-mediated necrotizing myopathy (IMNM) - associated with:

   • Anti-HMGCR antibodies (statin-associated or idiopathic)
   • Anti-SRP antibodies
   • Connective tissue diseases
   • Cancer
   • Checkpoint inhibitors

2. Non-immune-mediated necrotizing myopathy - associated with:

   • Drugs/toxins
   • Dystrophies
   • Infections
   • Hypothyroidism

Treatment Approach

First-Line Treatment

• Corticosteroids: Prednisone 0.5-1 mg/kg/day as initial therapy 2
• Important note: Corticosteroid monotherapy is usually insufficient; 90% of patients require ≥2 immunotherapeutic agents 1

Second-Line/Combination Therapy

• Methotrexate: First-line immunosuppressant to combine with steroids 2
• Alternatives:
  • Azathioprine
  • Mycophenolate mofetil (particularly useful for both muscle and skin disease) 2

For Refractory Disease (inadequate response after 4-6 weeks)

1. Intravenous Immunoglobulin (IVIG):

   • Highly effective for HMGCR-positive IMNM
   • Patients treated with IVIG have higher odds of CK normalization at 6 months (OR 9.44) 3
   • IVIG monotherapy can induce marked improvements in CK (95.7% reduction by 6 months) and strength (76.9% achieving normal/near-normal by 6 months) 3

2. Rituximab: Consider for refractory disease (may take up to 26 weeks to work) 2

3. Other options:

   • TNF-α or IL-6 antagonists
   • Cyclophosphamide (for severe disease with major organ involvement) 2
   • JAK inhibitors (for progressive disease despite first treatment) 2

Specific Considerations for HMGCR-Positive IMNM

• Statin discontinuation: Immediate cessation of statin therapy if statin-associated 4
• IVIG: Consider as first-line therapy or early in treatment course 3
• Maintenance therapy: Long-term immunosuppression is often required as relapse occurs in 55% of patients during immunosuppressant taper or discontinuation 1

Monitoring and Follow-up

• Regular assessment of:

  • Muscle strength
  • Serial CK measurements (target low-normal range)
  • Functional status improvement
  • Ability to taper corticosteroids 2

• Annual assessment of disease damage using validated indices like the Myositis Damage Index 2

Predictors of Favorable Outcome

• Male sex
• Use of 2 or more immunotherapeutic agents within 3 months of onset 1

Supportive Care

• Physical therapy to prevent joint contractures and muscle atrophy
• Early referral to a physiatrist for appropriate assistive devices
• Individualized and supervised exercise program
• Symptomatic management of pain with acetaminophen or NSAIDs if no contraindications 2

Complications to Monitor

• Dysphagia and risk of aspiration pneumonia
• Cardiac complications (conduction defects, tachyarrhythmias)
• Respiratory complications
• Side effects of immunosuppressive therapy

Caution

Statin-associated autoimmune myopathy is a rare disorder requiring statin cessation and aggressive immunotherapy directed at the autoimmune process. Patients may benefit from referral to a neurologist specializing in neuromuscular disorders 4.