What is the treatment for Amyloid A (Amyloid A) induced peripheral neuropathy?

Treatment of Amyloid A Induced Peripheral Neuropathy

For Amyloid A induced peripheral neuropathy, treatment should include both disease-modifying therapy with TTR silencers and symptomatic management of neuropathic pain and autonomic dysfunction. 1

Disease-Modifying Therapy

TTR Silencers (First-Line for ATTRv Polyneuropathy)

• Patisiran: 0.3 mg/kg intravenous infusion every 3 weeks with premedication (corticosteroid, acetaminophen, antihistamines) 1
• Inotersen: Subcutaneous injection with monitoring for thrombocytopenia and glomerulonephritis 1
• Vutrisiran: 25 mg subcutaneous injection once every 3 months 2
• All TTR silencers require daily vitamin A supplementation (3,000 IU) 1, 2
• Early treatment is critical as patients treated earlier show better neuropathy outcomes and quality of life 1

TTR Stabilizers

• Diflunisal: Shown to slow progression of ATTRv polyneuropathy but not FDA-approved for this indication 1
• Tafamidis: Approved for ATTR-CM but not FDA-approved for ATTRv polyneuropathy in the US (approved in Europe) 1

Symptomatic Management

Neuropathic Pain Treatment

• Pregabalin: First-line for sensory neuropathy symptoms 1
• Gabapentin: Alternative first-line for sensory neuropathy 1
• Duloxetine: Alternative for neuropathic pain 1
• Tricyclic antidepressants: Use with caution due to potential exacerbation of orthostatic hypotension and autonomic symptoms 1

Autonomic Dysfunction Management

• Orthostatic hypotension:
  • Non-pharmacological: Increased salt/fluid intake, compression stockings, abdominal binders 1, 3
  • Pharmacological options:
    • Fludrocortisone: Starting at 0.05-0.1 mg daily, titrated up to 0.1-0.3 mg daily 1, 3
    • Midodrine: For refractory orthostatic hypotension 1
    • Droxidopa: Alternative for orthostatic hypotension 1
    • Pyridostigmine: Preferred in patients with cardiac involvement as it doesn't cause fluid retention 1

Special Considerations

For AL Amyloidosis with Neuropathy

• Plasmapheresis: Consider for aggressive, progressing neuropathy (typically 2-3 months of weekly treatments) 1
• Rituximab: Consider as first intervention for mild, slowly progressive neuropathy 1
• Combination therapy (cyclophosphamide, prednisone, and rituximab or rituximab, cyclophosphamide, and dexamethasone): For moderate to severe neuropathy 1
• High-dose melphalan followed by autologous stem cell transplantation: Promising therapy for primary AL amyloid polyneuropathy 4

Important Caveats

• TTR silencers are only proven effective for ATTRv polyneuropathy, not for ATTRwt amyloidosis or other amyloid-related conditions 1, 2
• Medications for autonomic symptoms may be poorly tolerated in patients with cardiac involvement due to restrictive physiology 1
• Avoid digoxin and calcium channel antagonists in patients with cardiac amyloidosis 1
• Monitor for bortezomib-related peripheral neuropathy when used for treatment of underlying plasma cell dyscrasia 1
• Early diagnosis is crucial as peripheral neuropathy may be an early marker of amyloidosis, preceding other organ involvement by years 5

Treatment Algorithm

1. Confirm type of amyloidosis (AL vs. ATTR) through appropriate testing 1, 6
2. Initiate disease-modifying therapy based on amyloid type:
   • For ATTRv: Start TTR silencer (patisiran, inotersen, or vutrisiran) 1, 2
   • For AL: Treat underlying plasma cell dyscrasia 1, 4, 7
3. Concurrently manage symptoms:
   • For neuropathic pain: Start pregabalin or gabapentin 1
   • For autonomic dysfunction: Begin with non-pharmacological measures, then add medications as needed 1, 3
4. Regular monitoring of disease progression and treatment response using standardized measures (Neurologic Impairment Score, quality of life assessments) 1, 6