Teresa Coelho1, Mónica Inês1, Isabel Conceição1, Marta Soares1, Mamede de Carvalho1, João Costa2. 1. From the Andrade's Center for Familial Amyloidosis and Department of Neurosciences (T.C.), Hospital de Santo António, Centro Hospitalar do Porto; Instituto de Medicina Molecular (M.I., I.C., M.d.C., J.C.), Laboratório de Farmacologia Clínica e Terapêutica (J.C.), and Centro de Estudos de Medicina Baseada na Evidência (J.C.), Faculdade de Medicina, Universidade de Lisboa; Department of Neurosciences and Mental Health (I.C., M.d.C.), Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal; and Centre for Health Economics (M.S.), University of York, UK. 2. From the Andrade's Center for Familial Amyloidosis and Department of Neurosciences (T.C.), Hospital de Santo António, Centro Hospitalar do Porto; Instituto de Medicina Molecular (M.I., I.C., M.d.C., J.C.), Laboratório de Farmacologia Clínica e Terapêutica (J.C.), and Centro de Estudos de Medicina Baseada na Evidência (J.C.), Faculdade de Medicina, Universidade de Lisboa; Department of Neurosciences and Mental Health (I.C., M.d.C.), Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal; and Centre for Health Economics (M.S.), University of York, UK. jncosta@medicina.ulisboa.pt.
Abstract
OBJECTIVE: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met. METHODS: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios, Kaplan-Meier, and Cox methods were used to estimate excess mortality, survival, and adjusted hazard ratios (HRs) for all-cause mortality. RESULTS: Disease-modifying treatments decreased TTR-FAP excess mortality from 10 to 4 (standardized mortality ratio 3.92, 95% confidence interval [CI] 2.64-5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14-11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Among early-onset patients (younger than 50 years of age), tafamidis reduced the mortality risk compared with untreated patients by 91% (HR 0.09, 95% CI 0.03-0.25, p < 0.001) and with LTx-treated patients by 63% (HR 0.37, 95% CI 0.14-1.00, p = 0.050). Previous tafamidis treatment did not affect mortality risk after LTx (HR 0.83, 95% CI 0.25-2.78, p = 0.763). Among late-onset patients (50 years and older), tafamidis reduced mortality risk by 82% compared with untreated patients (HR 0.18, 95% CI 0.06-0.49, p = 0.001). CONCLUSION: LTx and tafamidis convey substantial survival benefits, but TTR-FAP mortality remains higher than in the general population. These results strongly reinforce the importance of timely diagnosis and earlier treatment, boosting the pursuit for an increased life expectancy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with stage 1 Val30Met TTR-FAP, LTx and tafamidis increase survival.
OBJECTIVE: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met. METHODS: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios, Kaplan-Meier, and Cox methods were used to estimate excess mortality, survival, and adjusted hazard ratios (HRs) for all-cause mortality. RESULTS: Disease-modifying treatments decreased TTR-FAP excess mortality from 10 to 4 (standardized mortality ratio 3.92, 95% confidence interval [CI] 2.64-5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14-11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Among early-onset patients (younger than 50 years of age), tafamidis reduced the mortality risk compared with untreated patients by 91% (HR 0.09, 95% CI 0.03-0.25, p < 0.001) and with LTx-treated patients by 63% (HR 0.37, 95% CI 0.14-1.00, p = 0.050). Previous tafamidis treatment did not affect mortality risk after LTx (HR 0.83, 95% CI 0.25-2.78, p = 0.763). Among late-onset patients (50 years and older), tafamidis reduced mortality risk by 82% compared with untreated patients (HR 0.18, 95% CI 0.06-0.49, p = 0.001). CONCLUSION:LTx and tafamidis convey substantial survival benefits, but TTR-FAP mortality remains higher than in the general population. These results strongly reinforce the importance of timely diagnosis and earlier treatment, boosting the pursuit for an increased life expectancy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with stage 1 Val30MetTTR-FAP, LTx and tafamidis increase survival.
Authors: Simoneide S Titze-de-Almeida; Pedro Renato de Paula Brandão; Ingrid Faber; Ricardo Titze-de-Almeida Journal: Mol Diagn Ther Date: 2020-02 Impact factor: 4.074
Authors: Cecília Monteiro; Jaleh S Mesgazardeh; João Anselmo; Joana Fernandes; Marta Novais; Carla Rodrigues; Gabriel J Brighty; David L Powers; Evan T Powers; Teresa Coelho; Jeffery W Kelly Journal: JCI Insight Date: 2019-06-20
Authors: Xin Jiang; Richard Labaudinière; Joel N Buxbaum; Cecília Monteiro; Marta Novais; Teresa Coelho; Jeffery W Kelly Journal: Proc Natl Acad Sci U S A Date: 2021-03-02 Impact factor: 11.205