Pain High Among Quality of Life Hindrances in FAP, Study Finds

The progressive nature of hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN), also known as familial amyloid polyneuropathy (FAP), limits patients’ health-related quality of life across all measures, with pain a particular problem, and is linked to depression or anxiety in carriers, a study from Portugal found.

Earlier diagnosis and treatment may help patients dealing with FAP’s progressive symptoms and considerable disability, and greater attention should be given to people without symptoms who carry the disease-causing mutation, its researchers said.

The study, “Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study,” was published in the Orphanet Journal of Rare Diseases.

Around 10,000 people worldwide are estimated to have FAP. But the largest concentration of these people is in Portugal, where the Val30Met mutation is found in almost all (more than 99%) family members of a patient. (The Val30Met mutation in the TTR gene is the most common cause of FAP, and the most prevalent mutation of Portuguese patients.)

Symptom onset among Portugese patients, the study reported, usually occurs between the ages of 28 and 42. In the absence of treatment, the disease moves through its stages steadily and can be fatal within about 12 years.

Researchers at several Portuguese institutions set out to gauge the impact of FAP on the health-related quality of life (HRQoL) of both patients and carriers, as well as to assess prognostic factors such as disease progression and treatment.

Their observational study included 621 asymptomatic carriers — individuals with the mutation and at risk of developing FAP — and 733 symptomatic patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS, NCT00628745).

THAOS is a registry collecting patient information, disease characteristics, treatment use, family history, biopsy results, and routine clinical data that includes information reported on a health-related quality of life EQ-5D-3L questionnaire.

Researchers also included, for comparison, data from 1,500 adults among the general population.

All FAP patients showed some degree of impairment in all EQ-5D-3L dimensions — mobility, self-care, pain and discomfort, usual activities, and anxiety or depression — with a health status significantly worse than the general population.

Symptomatic patients reported the greatest impact in terms of pain/discomfort (70% of this group), anxiety/depression (57%), and curtailed usual activities (44%). In carriers, the most affected dimension was anxiety/depression (39%).

“Older age, female sex, lower educational attainment and symptomatic disease were associated with poorer HRQoL,” the study reported.

Participants’ responses were then used to generate an EQ-5D-3L index score, called a utility score, against a composite “person” of the general population, to reflect their perceived health status.

This utility score was estimated to be 0.51 overall, 0.27 points less than this general population composite, a clinically meaningful difference reported across all age and gender groups.

It was also found to be lower for FAP patients than individuals with other chronic diseases, such as heart failure (0.63) and rheumatoid arthritis (0.62). Among FAP patients, the utility estimates ranged from 0.63 among those with stage 1 disease, to 0.01 in those with stage 4, according to the modified Polyneuropathy Disability scoring system (a measure of FAP progression).

Although no differences in utility estimates were found between carriers and the general population, the probability of carriers experiencing anxiety/depression was higher.

“This result reinforces the impact that emotional and psychological factors may have, not only among patients but also among carriers of the disease-causing mutation,” researchers wrote.

Notably, carriers reported less pain/discomfort in comparison to the general population, which researchers suggested may be due to disease denial or to carriers having different standards for these dimensions, as they often live with relatives who have the disease.

Older age (over 70), lower levels of education, higher disease duration, no treatment, and a higher disease stage were all associated with a lower HRQoL.

“The HRQoL among untreated patients was found deteriorating over time, while treated patients increased and preserved their HRQoL through the years,” the investigators wrote.

“In the case of hATTR-PN patients, we can conclude that clinical strategies focused on quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate and early treatment would largely benefit patient’s long-term outcomes,” they added.