What is the treatment for secondary amyloidosis?

Treatment of Secondary Amyloidosis

The most effective treatment for secondary amyloidosis is complete suppression of the underlying inflammatory disease that causes the production of serum amyloid A protein, using targeted therapies specific to the underlying condition. 1

Understanding Secondary Amyloidosis

Secondary amyloidosis (AA amyloidosis) results from chronic inflammatory conditions causing elevated serum amyloid A (SAA) protein, which deposits in organs as amyloid fibrils. The most commonly affected organs include:

• Kidneys (presenting as proteinuria and renal dysfunction)
• Gastrointestinal tract
• Liver
• Spleen
• Heart (less commonly than in other forms of amyloidosis)

Treatment Approach

1. Treat the Underlying Inflammatory Disease

The primary goal is to suppress the inflammatory activity causing SAA production:

• For Familial Mediterranean Fever (FMF):

  • Colchicine is the cornerstone treatment (1.0-1.5 mg/day for adults)
  • Complete suppression of inflammatory activity can prevent progression or even reverse established amyloidosis 1
  • Increase colchicine dose if inflammation persists (by 0.5 mg/day increments)

• For Inflammatory Bowel Disease:

  • Aggressive treatment of active IBD using appropriate therapies
  • Anti-TNF agents may have a direct effect on serum amyloid protein levels 1

• For Rheumatoid Arthritis and other rheumatic diseases:

  • Biologic therapies targeting inflammatory pathways:
    • IL-6 inhibitors (tocilizumab) have shown dramatic resolution of proteinuria 2, 3
    • TNF inhibitors (adalimumab) may be effective in some cases 4

2. Specific Therapy for Established Amyloidosis

For patients with established organ damage from amyloid deposits:

• Maximum tolerated dose of colchicine supplemented with biologics as required for patients with FMF-related amyloidosis 1

• IL-1 blockade (rilonacept) for colchicine-resistant patients with FMF 1

• Dimethyl sulfoxide (DMSO) has shown effectiveness in 66.7% of patients with AA amyloidosis, particularly for gastrointestinal involvement and early-stage renal dysfunction 5

• Daratumumab or daratumumab-based therapy is recommended for AL amyloidosis but not specifically indicated for AA amyloidosis 1, 6

3. Supportive Care for Organ Dysfunction

• For renal disease:

  • Blood pressure control
  • Dialysis for patients with end-stage renal disease
  • Renal transplantation in selected patients (survival now comparable with age-matched general transplant population) 1

• For hepatic involvement:

  • Monthly monitoring of CBC, basic biochemistry, and other relevant parameters 6

Monitoring Treatment Response

• Monitor SAA protein and CRP levels with target SAA below 10 mg/L 1
• Regular assessment of proteinuria and glomerular filtration rate
• Avoid nephrotoxic drugs, hypoperfusion, and hypertension in patients with amyloidotic kidneys 1
• Monitor liver enzymes regularly in patients treated with colchicine 1

Special Considerations

• Amyloidotic kidneys are unusually sensitive to additional injury from hypoperfusion, hypertension, nephrotoxic drugs, and surgery 1
• Living donor renal transplants have shown encouraging outcomes in selected patients 1
• Physical or emotional stress can trigger inflammatory attacks in FMF patients, requiring temporary increase in colchicine dose 1

Prognosis

With appropriate treatment of the underlying inflammatory disease, the prognosis of secondary amyloidosis has significantly improved. Colchicine has reduced the risk of developing amyloidosis in FMF from 60% to less than 13% 1. Early diagnosis and aggressive treatment are essential to prevent irreversible organ damage.