Dataset Information

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study.

ABSTRACT: BACKGROUND:Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment. METHODS:This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3?L. For general population the dataset included all subjects enrolled in a representative national study (n?=?1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates. RESULTS:Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p?=?0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p?=?0.910) or between late (?50?years) and early-onset patients (p?=?0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV. CONCLUSIONS:Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient's health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient's long-term outcomes, slowing the progressive decline in health-related quality of life.

SUBMITTER: Ines M

PROVIDER: S-EPMC7060628 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study.

Inês Mónica M Coelho Teresa T Conceição Isabel I Ferreira Lara L de Carvalho Mamede M Costa João J

Orphanet journal of rare diseases 20200306 1

<h4>Background</h4>Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic ...[more]

PMID: 32143656

Similar Datasets

Project description:IntroductionHereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study.MethodsThe phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed.ResultsAt month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: -21.0; p = 1.84 × 10-10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I-II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10-7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10-7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10-15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10-15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo.ConclusionVutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment.Trial registration numberClinicalTrials.gov: NCT03759379.

Project description:BackgroundHereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology.MethodA multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland.ResultsA total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants (TTR-positive) were identified. Body Mass Index was lower in the TTR-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR-positive patients.ConclusionsOur data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.

Project description:ObjectiveHereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare disease characterized by rapid neuropathic progression. In pivotal studies of gene-silencing treatments, the modified Neuropathy Impairment Score + 7 tests (mNIS + 7) and Norfolk-Quality of Life (QOL)-Diabetic Neuropathy (DN) questionnaire assessed treatment impact on neuropathic progression. Establishing responder definition (RD) thresholds for these measures would enable evaluation of clinically meaningful treatment benefit.MethodsmNIS + 7 and Norfolk-QOL-DN were administered at baseline and week 65 to 165 adults with ATTRv-PN receiving inotersen (n = 106) or placebo (n = 59) in the NEURO-TTR study. Anchor-based approaches for estimating RD thresholds were used for Norfolk QOL-DN, while distribution-based approaches were used for both measures. Responders were patients with a score change < RD, indicating improvement or stabilization (i.e., no clinically meaningful progression). Odds ratios (ORs) and Fisher's exact tests compared proportions of responders by treatment.ResultsThe mean RD estimates were 12.2 points and 8.8 points for mNIS + 7 and Norfolk QOL-DN, respectively. The proportions of patients whose change in score indicated improvement or stabilization were statistically significantly larger for inotersen than placebo for all estimated RD thresholds for mNIS + 7 (64-86% responders for inotersen vs. 27-46% for placebo, ORs = 3.8-7.2, ps < 0.001) and Norfolk QOL-DN (66-81% vs. 35-56%, ORs = 2.4-3.6, ps < 0.05).DiscussionEstablishing RD thresholds for these instruments enables evaluation of clinically relevant and individual-level treatment benefit on neuropathic progression. Across RDs estimated using multiple methods, a higher proportion of patients receiving inotersen than placebo showed improved or stabilized neuropathic progression at week 65.Trial registrationClinicalTrials.gov Identifier: NCT01737398; Date of registration: November 29, 2012.

Project description:IntroductionPatients with hereditary transthyretin amyloidosis associated with polyneuropathy (ATTRv-PN) experience deterioration in health-related quality of life (HRQOL) as the disease progresses. Findings from the randomized placebo-controlled phase III NEURO-TTR study showed treatment benefit of inotersen, an antisense oligonucleotide, for preserving or improving HRQOL after 65 weeks of treatment. The current analysis examines longitudinal trends in specific aspects of HRQOL, including polyneuropathy symptoms, daily activities, and physical, role, and social functioning in patients with ATTRv-PN receiving long-term treatment in a follow-up open-label extension (OLE) study.MethodsOne-hundred thirty-five patients with ATTRv-PN were enrolled in an ongoing 5-year OLE study following completion of NEURO-TTR. Eighty-five patients received continuous weekly treatment with inotersen in both studies (inotersen-inotersen group), while 50 patients switched from placebo to inotersen at OLE study baseline (placebo-inotersen group). Descriptive analyses of changes in domain scores and item responses through week 104 of the OLE study were conducted for measures of neuropathy-related and generic HRQOL: Norfolk QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2® Health Survey (SF-36v2), respectively.ResultsFor both inotersen-inotersen and placebo-inotersen groups, all Norfolk QOL-DN and most SF-36v2 domain scores remained stable from OLE baseline through week 104. Differences in HRQOL between the two groups at OLE baseline were sustained through week 104. Analysis of item responses from NEURO-TTR baseline to OLE study week 104 (170 weeks) for the inotersen-inotersen group found no notable increases in the proportion of patients reporting substantial impairments across a wide variety of symptoms, daily activities, and functioning.ConclusionLong-term treatment with inotersen preserved HRQOL for patients with ATTRv-PN for periods of up to 3 years. The gap in HRQOL between those who had previously received inotersen or placebo in NEURO-TTR did not close by week 104 of the OLE phase, indicating the importance of early treatment for maintaining HRQOL in these patients.Trial registrationClinicalTrials.gov Identifiers NCT01737398 for NEURO-TTR study; NCT02175004 for OLE study INFOGRAPHIC.

Dataset Information

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study.

Publications

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets