hATTR: An Ultra-Rare Disease Requiring Aggressive Early Intervention


Most Americans have never heard of hereditary transthyretin amyloidosis (hATTR), which speaks to its very low incidence rate in the population.

Most Americans have never heard of hereditary transthyretin amyloidosis (hATTR), which speaks to its very low incidence rate in the population. Approximately 50,000 people are affected globally, jettisoning hATTR into the ultra-rare category. This systemic amyloidosis is inherited in an autosomal dominant pattern, and a mutation produces misfolded amyloid proteins.

These abnormally shaped proteins often deposit or cluster in the nervous system or Sami Khella, MD organs. Their accumulation, usually affected once individuals become adults, may cause a broad range of symptoms.

On Tuesday, 2 experts in the field discussed treatment of hATTR at the Asembia Specialty Pharmacy Summit 2019. Sami Khella, MD, covered the clinical aspects of hATTR. He noted that amyloid diseases are classified based on several factors—including whether they are acquired or inherited, systemic or local—and have unique clinical patterns.

Symptoms appear to be genotype specific and frequently result in polyneuropathy, autonomic neuropathy, or cardiomyopathy. Many organ systems are affected. For example, they may have ocular manifestations (eg, vitreous opacification, abnormal conjunctival vessels) or gastrointestinal manifestations (eg, early satiety, nausea, vomiting, alternating episodes of diarrhea and constipation) that can be severely debilitating. Some of the most serious symptoms are difficulty walking and neuropathic pain.

Khella covered red flag symptoms associated with this disease, indicating they appear in clusters and need to be addressed with great urgency because delay in diagnosis leads to worse prognosis. e stressed that patients need targeted therapies and a wide range of symptomatic support. Until recently, patients with this genetic disease had few treatment options. The approvals of inotersen (Tegsedi) and patisiran (Onpattro) have changed that. These agents are indicated for the treatment of polyneuropathy of hATTR in adults.

Karen C. Thomas, PharmD, PhD, DABAT, gave a concise but thorough review of considerations for managing rare diseases, in particular reviewing the prevalence of hATTR and its associated costs. She noted that transthyretin amyloidosis (ATTR) mutations vary, and geneticists have identified more than 120 types, which supports the patient-specific variability in symptoms highlighted by Dr. Khella. Once symptoms occur, the patient’s prognosis may range from 3 to 15 years.

In the United States, the median age of onset is 68 years, with men almost 5 times more likely to develop the disease than women. In other countries, onset tends to be considerably earlier and the male:female ratio is close to 1. These differences in onset and gender ratios are attributable to geographic variability in the prevalence of ATTR genetic mutations.

As is the case with many rare diseases, cost estimates are difficult to pin down. Patients with hATTR are treated with the most expensive of orphan drugs. Depending on their disease progression and symptoms, many of these patients may need a liver transplant, an intervention that generally costs approximately $1.5 million. Medication can also be quite expensive. The disease course for each patient is unique, and not all will have the same needs.

Specialty pharmacists are faced with numerous decisions and dilemmas when patients need medications for hATTR, many of which were discussed by Thomas. She urged managed care professionals and pharmacists to identify patients who will have high utilization early in the process and to work very closely with other clinicians to elucidate special treatment requirements. These patients must absolutely engage with case management teams, and specialty pharmacists need to manage patient expectations so that they identify realistic treatment goals.

Managed care organizations and pharmacists need to be aware that IBD creates a significant financial burden for patients and caregivers. These patients may need housing adjustments (eg, ramps, elevators, and appliances) and to visit health care providers with great frequency. Caregivers assume much of this burden when they need to provide support or transportation.

The speakers urged specialty pharmacists to advocate for these patients and promote early diagnosis and aggressive treatment.

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