Amyloidosis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]

Overview[edit | edit source]

There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of organ failure.

Medical Therapy[edit | edit source]

Primary Amyloidosis (AL):[edit | edit source]

Some patients with primary amyloidosis respond to chemotherapy focused on the abnormal plasma cells. A stem cell transplant may be done, as in multiple myeloma.

• The initial step in the treatment of this disorder is to correct the organ failure, since the disease is discovered at an advanced stage when multiple organ systems may be affected.
  • Nephrotic syndrome is treated using supportive therapy and diuretics.
  • Renal failure is treated with dialysis.
  • Heart failure is treated using diuretics.
  • Gastrointestinal and nerve involvement are treated symptomatically.

The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.^[1]

Treatment options with limited success include melphalan, prednisone, and colchicine.

Secondary Amyloidosis (AA):[edit | edit source]

• Medical or surgical treatment of the underlying chronic infection or inflammatory disease is recommended among all patients who develop AA amyloidosis.
• Aggressively treating the disease that is causing the excess amyloid protein can improve symptoms and slow down or halt the progression of the disease.
• Complications such as heart failure, renal failure, and other problems can sometimes be treated, when needed.
• Although the choice of therapy depends on the underlying cause of chronic inflammation, the aim is always to suppress production of SAA to within the normal range.
• Examples of treatments for the commonest disorders underlying AA amyloidosis:^[4]

• Long-term inflammatory control can be accompanied by gradual regression of amyloid deposits and improvement in renal function.
• Currently a second clinical trial is in progress in order to evaluate a targeted inhibitor molecule, Kiacta, in the management of secondary amyloidosis.
• Novel therapies aimed at promoting clearance of existing amyloid deposits soon may be an effective treatment approach.

Wild-Type or Senile Amyloidosis (ATTRwt):[edit | edit source]

• Treatment is generally aimed at the symptoms of wild-type ATTR amyloidosis, such as treating amyloid deposits in the heart.
  • Because the heart is the most commonly affected organ, your disease will be monitored and treated by a cardiologist.
• For some patients with severe wild-type (senile) ATTR amyloidosis, a heart transplant may be the best option. Stanford is one of the world's leading centers for heart transplantation for amyloidosis.
• In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo.^[5]
• In ATTRwt amyloidosis, therapy is supportive, but both for this disease and for ATTR, pharmacologic therapies aimed at stabilizing the transthyretin molecule and thus preventing amyloid formation are being actively investigated.

Familial Amyloidosis (ATTR):[edit | edit source]

• The optimal therapy for familial amyloidosis is removal of the source of abnormal TTR production.
  • The liver is the dominant source of transthyretin; hence, in patients with less advanced disease, liver transplant may be performed.
  • Patients with severe heart involvement may benefit from a heart transplant.
• In addition, multiple clinical trials are now testing medications that may slow or halt progression of familial ATTR amyloidosis.
  • Tafamidis is a drug recently approved for familial amyloid polyneuropathy (FAP) in Europe.^[6]
    • This agent is being tested in ongoing trials for other forms of ATTR.
  • Patisiran and Inoteresen are TTR gene silencers. Recently FDA approved their use for ATTRm amyloidosis with peripheral neuropathy.^[7]
• Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members.

Dialysis-related amyloidosis (β2-microglobulin)[edit | edit source]

• There is no specific medical treatment for DRA.
• However, removal of significant amounts of beta2-microglobulin (beta2-m) may prevent or slow progression of the disease.
• This can be accomplished best by kidney transplantation.
• Other treatment opitons include:
  • Hemodialysis with a biocompatible high-flux dialysis membrane, hemodiafiltration
  • The use of ultrapure dialysate
  • A beta2-m adsorbent column may also result in lowering the level of beta2-microglobulin.
• Kidney transplantation is considered the definitive treatment for DRA in patients with end-stage renal disease.

References[edit | edit source]

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