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Background: Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available., Methods: In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy., Results: 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants ( n  = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p  = .007), significant weight loss (33 vs 11%, p  = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p  = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives., Conclusion: In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.

Background: Amyloidosis is a complex group of rare conditions. For patients, amyloidosis is severely debilitating: physically and psychologically. Currently, data are lacking to evaluate the medical, economic, and social burden of systemic amyloidosis., Objective: To analyse the patient burden according to the main types of systemic amyloidosis., Methods: The French Daily Impact of Amyloidosis study was an observational, cross-sectional and non-interventional study. Adults diagnosed with light chain (AL), transthyretin (ATTR), amyloid A (AA) and other rare forms of amyloidosis were eligible. Data regarding amyloidosis prevalence, diagnosis, management, and impact on everyday life were collected using a study-specific survey built by the Association Française Contre l'Amylose (AFCA) and the four French National Referral Centres for Amyloidosis., Results: A total of 603 patients, predominantly male (65%) with an average age of 66.8 years, including 170 AL, 224 ATTRv, 109 ATTRwt and 25 AA amyloidosis patients, completed the study-specific survey. The median delay from presentation to confirmed diagnosis was 27.4 months but varied according to amyloidosis type. Patients before diagnosis had breathlessness (49%), tingling sensation (33%), pain (28%), difficulty in walking (28%) and weight loss (22%). Amyloidosis was most frequently suspected (49%) and confirmed (57%) in local hospitals but managed in French amyloidosis referral centres (58%). Patients often reported problems with mobility, usual activities, pain/discomfort and anxiety/depression, but not with self-care., Conclusions: Systemic amyloidosis severely impacts daily life. The delay to confirmed amyloidosis diagnosis needs to be reduced. Early, effective treatment is required to optimise patient benefits.

Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated. Methods: Patients received either patisiran 0.3 mg/kg ( n  = 148) or placebo ( n  = 77) intravenously once every three weeks for 18 months. Multiple measures were used to assess varying aspects of QOL. Results: At 18 months, compared with placebo, patisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score; (least squares [LS] mean difference: -21.1; p  = 1.10 × 10 -10 ; improved across all domains), EuroQoL 5-dimensions 5-levels (LS mean difference: 0.2; p  = 1.4 × 10 -12 ), EuroQoL-visual analog scale (LS mean difference: 9.5; p =.0004), Rasch-built Overall Disability Scale (LS mean difference: 9.0; p  = 4.07 × 10 -16 ) and Composite Autonomic Symptom Score-31(COMPASS-31; LS mean difference: -7.5; p =.0008). Placebo-treated patients experienced rapid QOL deterioration; treatment effects for patisiran were observed as early as 9 months. At 18 months, patisiran improved Norfolk QOL-DN total score and three individual domains as well as COMPASS-31 total scores relative to baseline. Consistent benefits were also observed in the cardiac subpopulation. Conclusion: The benefits of patisiran across all QOL measures and the rapid deterioration observed with placebo, highlight the urgency in early treatment for patients with hATTR amyloidosis with polyneuropathy.

Background: Transthyretin-related amyloidosis (ATTR) is an autosomal dominant disease affecting the peripheral and autonomic nervous system, heart, eyes and kidneys. It is the most disabling hereditary polyneuropathy in adults. The French National Reference centre for this disease was accredited in 2005 with 10 lines of action. One of them is to inform and educate patients about their disease to improve their care and reduce morbidities. We thus decided to elaborate a therapeutic patient education (TPE) programme, starting with patients' needs assessment., Methods: A qualitative research study was conducted with one-to-one semi-structured interviews of selected individuals. Recorded interviews were analysed to identify the skills that patients need to acquire. A TPE programme was elaborated on the basis of these findings., Results: Seven patients, one asymptomatic carrier and two healthy spouses were interviewed. Analysis of the interviews showed that interviewees had a good knowledge of the disease and its symptoms but they had difficulties explaining the disease mechanism and did not have an adequate knowledge of the available treatment options, although they knew that liver transplant might halt progression of the disease. ATTR amyloidosis appeared to have a major negative impact on the patient's physical and mental well-being. Patients feared loss of autonomy and having to require assistance from their relatives and spouses. All interviewees were keen to participate in a TPE programme. Based on this needs assessment, we identified seven skills that patients need to acquire and several pedagogical goals to be achieved during the education programme. An interdisciplinary team then elaborated a complete TPE programme., Conclusion: Elaboration of a TPE programme for ATTR amyloidosis required to obtain useful information from the patients themselves, and their relatives, concerning their perception of their disease. This needs' assessment constituted the basis for designing the first TPE programme, to our knowledge, for ATTR amyloidosis. After translation, this programme could be applied in other EU countries and worldwide for this rare disease.