This activity was funded by Alnylam Pharmaceuticals. The medical content was developed independently by M3 and Professor Violaine Planté-Bordeneuve.

Highlights from

Amyloidosis Conferences



What can we learn from patient-reported outcomes in hATTR amyloidosis?

Take-home messages
  • PROs can inform management and treatment of patients with hATTR amyloidosis
  • Delays in treatment initiation for hATTR amyloidosis correlate with poor PROs
  • Gene silencing therapies for hATTR amyloidosis have high levels of patient-reported satisfaction

Hereditary transthyretin-mediated (hATTR) amyloidosis is a systemic disease caused by the deposits of amyloid fibrils (aggregates of misfolded variant transthyretin (TTR) protein) in organs throughout the body.1 It commonly affects the peripheral nervous system and the heart, with a notable impact on the autonomic nervous system,2 that can be fatal. However, new and existing treatments have the potential to change the trajectory of disease.1 Symptoms have a large negative impact on quality of life (QOL) for patients with hATTR amyloidosis and, increasingly, QOL is being considered as an important outcome for the management of patients.2

Two posters at the 7th Congress of the European Academy of Neurology (EAN) – Virtual 2021, authored by Dr Duncan Brown, Health Economics and Outcomes Research Director at Akcea Therapeutics, covered patient-reported outcomes (PROs) from trials in patients with hATTR amyloidosis.

Time-to-treatment and PROs

Diagnosis in hATTR amyloidosis is often delayed, allowing for progression of the disease, with worsening neuropathy and QOL, before treatment is initiated. Current treatments can help stabilise hATTR amyloidosis but cannot reverse it.

Dr Brown presented the results of an online survey of 28 patients with hATTR amyloidosis from the US and Canada, who had been on continual treatment for at least 12 months, analysing the relationship between time-to-treatment (years between patient-reported symptom onset and initiation of therapy) and PROs. PRO measures included:

  • the Composite Autonomic Symptom Scale (COMPASS-31), which measures autonomic neuropathy
  • the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire, which measures neuropathy-related QOL
  • the SF-36v2 Health Survey which measures physical QOL

Treatments included inotersen only (n=3), inotersen and diflunisal (n=4), patisiran only (n=12), patisiran and diflunisal (n=2), tafamidis only (n=3), tafamidis and diflunisal (n=2), diflunisal only (n=1), doxycycline + tauroursodeoxycholic acid (TUDCA; n=1) and PRX004 diflunisal and doxycycline + TUDCA (n=1).

Moderate correlations were observed between the PROs and time-to-treatment, with a linear correlation between COMPASS-31 and time-to-treatment. The correlation was non-linear between time-to-treatment and both Norfolk QOL-DN and SF-36v2; rapid deterioration was observed for those patients with 4-5 years of treatment delay, after which it levelled off, perhaps suggesting that the limit of deterioration had been reached.

Dr Brown concluded that autonomic function and QOL rapidly worsen soon after symptom onset for patients with hATTR amyloidosis, adding that "Given the inability of current treatments to reverse deterioration, early diagnosis and treatment is essential to preserve functioning and QOL in patients with ATTR."

PROs and gene silencing pharmacotherapies

In 2018, two gene silencing therapies for the treatment of polyneuropathy in patients with hATTR amyloidosis were approved in the US and the UK: inotersen,3,4 a subcutaneous antisense oligonucleotide, and patisiran,5,6 an intravenous RNA interference therapy.

A 2-year, descriptive, non-interventional study was conducted using an online survey, to assess patient satisfaction with these two treatment options (n=11 for inotersen and n=18 for patisiran). Patients were asked about their hATTR amyloidosis-related polyneuropathy disease characteristics and treatment regimen, and completed the Treatment Satisfaction Questionnaire for Medication vII, which captures treatment satisfaction of patients' current medical treatments over the previous 2-3 weeks.

Overall, both treatments scored highly for treatment satisfaction and the patient-reported satisfaction with the effectiveness and overall treatment experience was similar between inotersen and patisiran. However, patients receiving inotersen scored more highly on average than patients receiving patisiran for convenience (76.3 vs 58.6) and satisfaction with side effects (86.1 vs 68.3). The higher levels of patient satisfaction for convenience reported with inotersen versus patisiran could be a result of the differing mode of administration for the two therapies (an injection administered at home vs an infusion administered at a clinic).

The speaker highlights that this descriptive analysis was conducted in a small sample of patients and, whilst it provides insight into the patient experience with inotersen and patisiran, it should be considered as "hypothesis generating" rather than fully representative of the patient experience.

Based on: Brown D, Sikora Kessler A et al. Patient-reported outcomes by time from symptom onset to first pharmacotherapy among transthyretin amyloidosis patients. ePoster-171 presented at the 7th Congress of the European Academy of Neurology (EAN) – Virtual 2021, 19-22 June 2021; Brown D, Sikora Kessler A et al. Treatment satisfaction for gene silencing pharmacotherapies in hereditary transthyretin amyloidosis with polyneuropathy. ePoster-170 presented at the 7th Congress of the European Academy of Neurology (EAN) – Virtual 2021, 19-22 June 2021

  1. Benson M D, Dasgupta N R, Rao R. Diagnosis and screening of patients with hereditary transthyretin amyloidosis (hATTR): current strategies and guidelines. Ther Clin Risk Manag 2020;16:749-758
  2. Gendre T, Plante-Bordeneuve V. Strategies to improve the quality of life in patients with hereditary transthyretin amyloidosis (hATTR) and autonomic neuropathy. Clin Auton Res 2019;29(Suppl 1):25-31
  3. Inotersen Summary of Product Characteristics. Available at: Accessed July 2021
  4. US Food and Drug Administration. Drug approval package: Tegsedi (inotersen), 1 November 2018. Available at: Accessed July 2021
  5. Patisiran Summary of Product Characteristics. Available at: Accessed July 2021
  6. US Food and Drug Administration. Drug approval package: Onpattro (patisiran), 7 September 2018. Available at: Accessed July 2021

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