What is the treatment for Transthyretin (ATTR) Amyloidosis?

From the Guidelines

Tafamidis is the recommended treatment for Transthyretin (ATTR) Amyloidosis, as it has been shown to improve cardiovascular outcomes and reduce mortality in patients with this condition. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, tafamidis is the only therapy that has been proven to improve cardiovascular outcomes in ATTR-CM. The ATTR-ACT clinical trial demonstrated that tafamidis had lower all-cause mortality and lower cardiovascular-related hospitalization compared to placebo.

The treatment approach for ATTR amyloidosis involves managing symptoms and addressing the underlying protein misfolding. For hereditary ATTR, liver transplantation has been a traditional approach to remove the source of mutant transthyretin protein. In addition to tafamidis, other medications such as patisiran (Onpattro) may be used to reduce transthyretin production. For cardiac ATTR, additional treatments include:

• Diuretics for fluid management
• Pacemakers for conduction abnormalities
• Careful blood pressure management

For neuropathic ATTR, pain management with gabapentin or pregabalin may be necessary. Diflunisal, an NSAID, can also stabilize transthyretin but must be used cautiously due to renal and gastrointestinal side effects. Treatment should be initiated early, as these medications primarily slow progression rather than reverse existing damage. A multidisciplinary approach involving cardiologists, neurologists, and genetic counselors is essential for comprehensive management of this complex disease, as highlighted in the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE TEGSEDI is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

1 INDICATIONS AND USAGE ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

1. INDICATIONS AND USAGE VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

The treatment for Transthyretin (ATTR) Amyloidosis includes:

• Inotersen (SQ) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults 2
• Patisiran (IV) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults 3
• Tafamidis (PO) for the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization 4

From the Research

Treatment Options for Transthyretin (ATTR) Amyloidosis

The treatment for Transthyretin (ATTR) Amyloidosis includes:

• Liver transplantation, which has been established as an effective treatment for hereditary transthyretin amyloidosis, particularly for patients with early-onset disease 5, 6
• Tafamidis, a TTR stabilizer that has been shown to be effective in reducing the progression of neuropathy and improving survival in patients with early-stage disease 7, 8, 6
• Diflunisal, a nonsteroidal anti-inflammatory drug that has been used off-label to treat ATTR amyloidosis, although its efficacy and safety are not well established 7, 6
• Patisiran, an RNA interference therapy that has been shown to reduce the production of transthyretin and slow the progression of neuropathy in patients with hereditary transthyretin amyloidosis 7, 8, 6
• Inotersen, an antisense oligonucleotide therapy that has been shown to reduce the production of transthyretin and slow the progression of neuropathy in patients with hereditary transthyretin amyloidosis 7, 8, 6

Disease-Modifying Treatments

Disease-modifying treatments for Transthyretin Amyloidosis focus on three mechanistic pathways:

• Silencing of the TTR gene to suppress production 9
• Stabilizing of TTR tetramers to prevent misfolding 9
• Disrupting of existing TTR amyloid fibrils to promote reabsorption 9

Therapeutic Insights

Recent developments in diagnostic techniques have significantly expanded the concept of Transthyretin Amyloidosis, and electron microscopic studies have shown that the direct impact of amyloid fibrils on surrounding tissues leads to organ damage 6. Gene-silencing drugs, such as patisiran and inotersen, seem to be the optimal therapeutic option for ATTR amyloidosis due to their ability to significantly reduce the production of both wild-type and variant TTR in the liver 6.