13 results on '"Barroso, Fabio"'
Search Results
2. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy.
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Coelho, Teresa, Marques Jr, Wilson, Dasgupta, Noel R., Chao, Chi-Chao, Parman, Yeşim, França Jr, Marcondes Cavalcante, Guo, Yuh-Cherng, Wixner, Jonas, Ro, Long-Sun, Calandra, Cristian R., Kowacs, Pedro A., Berk, John L., Obici, Laura, Barroso, Fabio A., Weiler, Markus, Conceição, Isabel, Jung, Shiangtung W., Buchele, Gustavo, Brambatti, Michela, and Chen, Jersey
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TRANSTHYRETIN ,POLYNEUROPATHIES ,CLINICAL trials ,AMYLOIDOSIS ,CARDIAC amyloidosis ,ARRHYTHMIA ,CEREBRAL hemorrhage - Abstract
Key Points: Question: Is the antisense oligonucleotide eplontersen associated with changes in serum transthyretin concentration and improvement in neuropathy symptoms among adults with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy? Findings: In this open-label study that enrolled 168 patients (144 assigned to subcutaneous eplontersen) and included 60 historical placebo patients, the eplontersen treatment group demonstrated changes from baseline to week 65/66 consistent with significantly lower serum transthyretin concentration (−81.7% vs −11.2%), less neuropathy impairment, and better quality of life compared with the historical placebo group. Meaning: Among adults with ATTRv polyneuropathy, the eplontersen treatment group had lower serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P <.001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10 This open-label, single-group, phase 3 trial evaluates eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with hereditary amyloid transthyretin (ATTRv) polyneuropathy at 40 sites in 15 countries, compared with historical controls. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen.
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Coelho, Teresa, Waddington Cruz, Márcia, Chao, Chi-Chao, Parman, Yeşim, Wixner, Jonas, Weiler, Markus, Barroso, Fabio A., Dasgupta, Noel R., Jung, Shiangtung W., Schneider, Eugene, Viney, Nicholas J., Dyck, P. James B., Ando, Yukio, Gillmore, Julian D., Khella, Sami, Gertz, Morie A., Obici, Laura, and Berk, John L.
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TRANSTHYRETIN ,ORGANS (Anatomy) ,PERIPHERAL nervous system ,POLYNEUROPATHIES ,LIVER transplantation ,AMYLOIDOSIS - Abstract
Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study. Methods: Patients eligible for NEURO-TTRansform were 18–82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II. Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0. Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice. Trial Registration: ClinicalTrials.gov identifier NCT04136184. Plain Language Summary: Hereditary transthyretin amyloidosis, also called ATTRv amyloidosis, is a rare and serious disease that is passed down within families. People with ATTRv amyloidosis have a genetic variant that causes their liver to make abnormal versions of the transthyretin protein (also known as "TTR"), which clump together into "clusters" called amyloids. The amyloid clusters build up in various body tissues and organs such as the liver, nerves, heart, and kidney, causing damage that could ultimately lead to death. ATTRv amyloidosis is a progressive disease, meaning that it gets worse over time. Liver transplant has traditionally been the only treatment option. Recently, drugs that target TTR have been approved by the FDA, and potential drugs are being tested in clinical trials. Eplontersen is designed to degrade TTR mRNA in the liver and inhibit the production of TTR protein. NEURO-TTRansform is a global phase 3 study investigating the effectiveness and safety of eplontersen in 168 adults with ATTRv amyloidosis with polyneuropathy (ATTRv-PN), a disease in which amyloid accumulation in peripheral nerves causes multisystem damage and eventually death. This scientific article describes the characteristics of the patients at enrollment, including age, gender, geographic location, and disease-related information, to help improve the understanding of ATTRv-PN. NEURO-TTRansform is an ongoing study, and the results will be published at a later time as prespecified in the analysis plan. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS)
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Dispenzieri, Angela, Coelho, Teresa, Conceição, Isabel, Waddington-Cruz, Márcia, Wixner, Jonas, Kristen, Arnt V., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Gonzalez-Moreno, Juan, Maurer, Mathew S., Grogan, Martha, Chapman, Doug, Amass, Leslie, Pavia, Pablo Garcia, Tarnev, Ivaylo, Costello, Jose Gonzalez, Briseno, Maria Alejandra Gonzalez Duarte, Schmidt, Hartmut, Drachman, Brian, Barroso, Fabio Adrian, Yamashita, Taro, Lairez, Olivier, Sekijima, Yoshiki, Vita, Giuseppe, Jeon, Eun-Seok, Hanna, Mazen, Slosky, David, Luigetti, Marco, LoRusso, Samantha, Beamud, Francisco Munoz, Adams, David, Moelgaard, Henning, Press, Rayomand, Cirami, Calogero Lino, Nienhuis, Hans, Plana, Josep Maria Campistol, Inamo, Jocelyn, Jacoby, Daniel, Emdin, Michele, Quan, Dianna, Hummel, Scott, Witteles, Ronald, Dori, Amir, Shah, Sanjiv, Lenihan, Daniel, Azevedo, Olga, Murali, Srinivas, Zivkovic, Sasa, Low, Soon Chai, Nativi-Nicolau, Jose, Fine, Nowell, Tallaj, Jose, Tschoepe, Carsten, Torrón, Roberto Fernandéz, Polydefkis, Michael, Merlini, Giampaolo, Badelita, Sorina, Gottlieb, Stephen, Tauras, James, Correia, Edileide Barros, Ventura, Hector, Gess, Burkhard, Darstein, Felix, Oh, Jeeyoung, Marburger, Tessa, Van Cleemput, Johan, Salutto, Valeria Lujan, Parman, Yesim, Chao, Chi-Chao, Sarswat, Nitasha, Mueller, Christopher, Steidley, David, Ralph, Jeffrey, Warner, Alberta, Cotts, William, Hoffman, James, Rugiero, Marcelo, Misawa, Sonoko, Blanco, Jose Luis Munoz, Davila, Lucia Galan, Sadeh, Menachem, Luo, Jin, Kyriakides, Theodoros, Wang, Annabel, and Kaufmann, Horacio
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Male ,Amyloid Neuropathies, Familial ,Registry ,Neurologi ,Cardiomyopathy ,General Medicine ,Amyloidosis ,Genetic Profile ,Amyloid Neuropathies ,Transthyretin ,Phenotype ,Familial ,Neurology ,Surveys and Questionnaires ,Polyneuropathy ,Humans ,Prealbumin ,Pharmacology (medical) ,Female ,Genetics (clinical) - Abstract
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.
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- 2022
5. Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS)
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Barroso, Fabio A., Coelho, Teresa, Dispenzieri, Angela, Conceição, Isabel, Waddington-Cruz, Marcia, Wixner, Jonas, Maurer, Mathew S., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Kristen, Arnt V., González-Duarte, Alejandra, Chapman, Doug, Stewart, Michelle, and Amass, Leslie
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Amyloid Neuropathies, Familial ,Neurology ,Neurologi ,Surveys and Questionnaires ,autonomic nervous system ,Internal Medicine ,Quality of Life ,Humans ,neuropathy ,Primary Dysautonomias ,Amyloidosis ,registry ,transthyretin - Abstract
Background: Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020). Results: Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]). Conclusions: Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT00628745.
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- 2022
6. Phenotypic Differences of Glu89Gln Genotype in ATTR Amyloidosis From Endemic Loci: Update From THAOS.
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Gentile, Luca, Tournev, Ivailo, Amass, Leslie, Chapman, Doug, Mazzeo, Anna, the THAOS investigators, Barroso, Fabio, van Cleemput, Johan, Schmidt, Hartmut, Gess, Burkhard, Garcia Pavia, Pablo, Blanco, José Luis Muñoz, Rapezzi, Claudio, Vita, Giuseppe, Merlini, Giampaolo, Luigetti, Marco, Parman, Yesim, Maurer, Mathew, and LoRusso, Samantha
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AMYLOIDOSIS ,PHENOTYPES ,LOCUS (Genetics) ,GENOTYPES ,CARDIAC amyloidosis ,DEMOGRAPHIC characteristics - Abstract
Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, clinically heterogeneous disease with spontaneous (wild-type) and hereditary (ATTRv) forms. The Glu89Gln variant is primarily associated with cardiomyopathy and prevalent in Italy and Bulgaria. The objective of this analysis was to better understand the profile of patients with ATTRv Glu89Gln amyloidosis in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Methods: THAOS is an ongoing, global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers with mutations in the transthyretin gene. Demographic and clinical characteristics of all symptomatic patients with the ATTRv Glu89Gln variant enrolled in THAOS are described (data cutoff, January 6, 2020). Results: There were 91 patients with ATTRv Glu89Gln amyloidosis with the majority from Bulgaria (n = 53) or Italy (n = 29). All patients were Caucasian and 50.5% were male. Patients from Bulgaria had a mean (standard deviation) age at enrollment of 57.1 (8.2) years, and duration of symptoms of 8.6 (9.6) years, compared with 54.8 (8.6) and 5.0 (4.1) years in Italy. In Bulgaria, 39.6% of patients were of a predominantly cardiac phenotype, 18.9% predominantly neurologic, and 41.5% mixed. In Italy, 3.4% of patients were predominantly cardiac, 62.1% predominantly neurologic, and 34.5% mixed. Conclusions: The majority of patients with ATTRv Glu89Gln amyloidosis in THAOS are from Bulgaria or Italy. There were notable phenotypic differences, with the cardiac phenotype more common in Bulgaria and the neurologic phenotype more common in Italy. Over one-third of patients had a mixed phenotype, suggesting a potential role of multiple genetic and/or environmental factors and the need for comprehensive assessment of all patients. Trial Registration: ClinicalTrials.gov: NCT00628745. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).
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Waddington-Cruz, Márcia, Wixner, Jonas, Amass, Leslie, Kiszko, Jan, Chapman, Doug, Ando, Yukio, the THAOS investigators, Barroso, Fabio Adrian, Rugiero, Marcelo, Van Cleemput, Johan, Tarnev, Ivaylo, Kyriakides, Theodoros, Kristen, Arnt, Schmidt, Hartmut, Darstein, Felix, Gess, Burkhard, Plana, Josep Maria Campistol, Moreno, Juan Gonzalez, Costello, Jose Gonzalez, and Pavia, Pablo Garcia
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CARDIAC amyloidosis ,AMYLOIDOSIS ,TRANSTHYRETIN ,TREATMENT effectiveness ,STANDARD deviations ,PATIENT surveys - Abstract
Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early- or late-onset disease. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late- (age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019). Results: Of 1389 patients with ATTRv Val30Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Late-onset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in late-onset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% early-onset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p < 0.001). Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to more timely diagnosis and improve patient outcomes. Trial Registration: ClinicalTrials.gov NCT00628745. [ABSTRACT FROM AUTHOR]
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- 2021
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8. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)
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Kristen, Arnt V., Maurer, Mathew S., Rapezzi, Claudio, Mundayat, Rajiv, Suhr, Ole B., Damy, Thibaud, Barroso, Fabio Adrian, Rugiero, Marcelo F, Van Cleemput, Johan J., Tournev, Ivailo, Cruz, Marcia Waddington, Fine, Nowell M., Kristen, Arnt Volko, Schmidt, Hartmut H. J., Zimmermann, Tim, Gess, Burkhard, Moelgaard, Henning, Plana, Josep Maria Campistol, Reines, Juan Buades, Costello, Jose Gonzalez, Pavia, Pablo Garcia, Blanco, Jose Luis Munoz, Plante Bordeneuve, Violaine, Adams, David, Inamo, Jocelyn, Vita, Giuseppe, Merlini, Giampaolo, Bergesio, Franco, Sekijima, Yoshiki, Ando, Yukio, Misawa, Sonoko, Lee, Ga Yeon, Jeeyoung, Oh, Briseno, Maria Alejandra Gonzalez Duarte, Hazenberg, Bouke P. C., Coelho, Teresa, Conceicao, Isabel M., Maurer, Mathew Shane, Shah, Sanjiv Jayendra, Quan, Dianna, Judge, Daniel Philip, Gottlieb, Stephen Scott, Sarswat, Nitasha, Murali, Srinivas C., Iyadurai, Stanley, Cotts, William Gerritt, Drachman, Brian M., Dispenzieri, Angela, Steidley, David Eric, Hummel, Scott L., Lenihan, Daniel J., Ventura, Hector Osvaldo, Jacoby, Daniel L., Hoffman, James E., Kristen, Arnt V., Maurer, Mathew S., Rapezzi, Claudio, Mundayat, Rajiv, Suhr, Ole B., Damy, Thibaud, Barroso, Fabio Adrian, Rugiero, Marcelo F, Van Cleemput, Johan J., Tournev, Ivailo, Cruz, Marcia Waddington, Fine, Nowell M., Kristen, Arnt Volko, Schmidt, Hartmut H.J., Zimmermann, Tim, Gess, Burkhard, Moelgaard, Henning, Plana, Josep Maria Campistol, Reines, Juan Buade, Costello, Jose Gonzalez, Pavia, Pablo Garcia, Blanco, Jose Luis Munoz, Plante-Bordeneuve, Violaine, Adams, David, Inamo, Jocelyn, Vita, Giuseppe, Merlini, Giampaolo, Bergesio, Franco, Sekijima, Yoshiki, Ando, Yukio, Misawa, Sonoko, Lee, Ga Yeon, Oh, Jeeyoung, Briseno, Maria Alejandra Gonzalez Duarte, Hazenberg, Bouke P.C., Coelho, Teresa, Conceicao, Isabel M., Maurer, Mathew Shane, Shah, Sanjiv Jayendra, Quan, Dianna, Judge, Daniel Philip, Gottlieb, Stephen Scott, Sarswat, Nitasha, Murali, Srinivas C., Iyadurai, Stanley, Cotts, William Gerritt, Drachman, Brian M., Dispenzieri, Angela, Steidley, David Eric, Hummel, Scott L., Lenihan, Daniel J., Ventura, Hector Osvaldo, Jacoby, Daniel L., Hoffman, James E., and Translational Immunology Groningen (TRIGR)
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Genetics and Molecular Biology (all) ,Pathology ,Physiology ,medicine.medical_treatment ,Peptide Hormones ,lcsh:Medicine ,Medicine (all) ,Biochemistry ,Agricultural and Biological Sciences (all) ,030204 cardiovascular system & hematology ,Liver transplantation ,Pathology and Laboratory Medicine ,Body Mass Index ,0302 clinical medicine ,Genotype-phenotype distinction ,Surveys and Questionnaires ,Genotype ,Natriuretic Peptide, Brain ,Natriuretic peptide ,Medicine and Health Sciences ,Atrial natriuretic peptides ,Cardiac and Cardiovascular Systems ,lcsh:Science ,Multidisciplinary ,Kardiologi ,biology ,Amyloidosis ,Biochemical markers ,Troponin ,Phenotype ,Physiological Parameters ,cardiovascular system ,Anatomy ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,medicine.medical_specialty ,medicine.drug_class ,Cardiology ,Surgical and Invasive Medical Procedures ,macromolecular substances ,NO ,03 medical and health sciences ,Digestive System Procedures ,Signs and Symptoms ,Troponin T ,Diagnostic Medicine ,Natriuretic Peptide ,medicine ,Humans ,cardiovascular diseases ,Heart Failure ,Amyloid Neuropathies, Familial ,Transplantation ,Biochemistry, Genetics and Molecular Biology (all) ,business.industry ,lcsh:R ,Troponin I ,Body Weight ,Biology and Life Sciences ,Proteins ,Renal System ,Organ Transplantation ,medicine.disease ,Hormones ,Liver Transplantation ,Transthyretin ,Cytoskeletal Proteins ,Heart failure ,biology.protein ,lcsh:Q ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
AIM:Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. METHODS AND RESULTS:Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Three-year overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p
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- 2017
9. Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial.
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Waddington-Cruz, Marcia, Ackermann, Elizabeth J., Polydefkis, Michael, Heitner, Stephen B., Dyck, Peter J., Barroso, Fabio A., Wang, Annabel K., Berk, John L., Dyck, P. James B., Monia, Brett P., Hughes, Steven G., Tai, Li, Jesse Kwoh, T., Jung, Shiangtung W., Coelho, Teresa, Benson, Merrill D., and Gertz, Morie A.
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TRANSTHYRETIN ,AMYLOIDOSIS ,GENETIC disorders ,NEUROPATHY ,CARDIOMYOPATHIES - Abstract
Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems. [ABSTRACT FROM AUTHOR]
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- 2018
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10. Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years.
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Barroso, Fabio A., Judge, Daniel P., Ebede, Ben, Li, Huihua, Stewart, Michelle, Amass, Leslie, and Sultan, Marla B.
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DRUG efficacy , *MEDICATION safety , *POLYNEUROPATHIES , *TRANSTHYRETIN , *DRUG tolerance , *THERAPEUTICS - Abstract
Background:The objective of the present study was to evaluate the long-term safety and efficacy of tafamidis in treating hereditary transthyretin amyloid polyneuropathy. Methods:A prospectively planned interim analysis was conducted on an on-going, phase III, open-label extension study following an 18-month, randomized, controlled study and 12-month, open-label extension study in ATTRV30M patients and a single-arm, open-label study in non-ATTRV30M patients. Thirty-seven ATTRV30M patients received placebo for 18 months, then switched to tafamidis and 38 ATTRV30M patients and 18 non-ATTRV30M patients continuously received tafamidis from day 1, up to 6 years. Results:Long-term tafamidis was associated with a favourable safety/tolerability profile, without any unexpected adverse events. Patients initiating tafamidis at the start of the randomized study had less polyneuropathy progression versus those switching to tafamidis following 18 months of placebo and were less likely to progress to the next ambulatory stage after up to 6 years follow-up. In the patients who switched from placebo to tafamidis, polyneuropathy progression and deterioration in quality of life slowed significantly during long-term tafamidis treatment as compared with the previous placebo treatment. In non-ATTRV30M patients, some polyneuropathy progression was observed across all efficacy measures. Conclusions:These data provide evidence for the long-term (up to 6 years) safety and efficacy of tafamidis.ClinicalTrials.gov:NCT00925002 [ABSTRACT FROM AUTHOR]
- Published
- 2017
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11. Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.
- Author
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Schmidt, Hartmut H.‐J., Barroso, Fabio, González‐Duarte, Alejandra, Conceição, Isabel, Obici, Laura, Keohane, Denis, and Amass, Leslie
- Abstract
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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12. Blood pressure and orthostatic hypotension as measures of autonomic dysfunction in patients from the transthyretin amyloidosis outcomes survey (THAOS).
- Author
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González-Duarte, Alejandra, Barroso, Fabio, Mundayat, Rajiv, and Shapiro, Bryan
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ORTHOSTATIC hypotension , *DYSAUTONOMIA , *BLOOD pressure , *AMYLOIDOSIS , *WEIGHT loss , *TRANSTHYRETIN - Abstract
Autonomic dysfunction, an early symptom of transthyretin amyloidosis (ATTR amyloidosis), requires investigations not readily available in many clinics. Although monitoring of orthostatic hypotension (OH) will not be a substitute for more specialized tests, it can add important information about initiation of dysautonomia. The aim of this study was to investigate whether simple blood pressure (BP) monitoring may be a useful tool for evaluation of disease progression and an early sign of autonomic dysfunction. BP and OH data were from subjects enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Characteristics associated with changes in BP and orthostatic difference were identified by regression analyses. OH tended to be present relatively early in the course of disease and was more common at enrollment (11.7%) than either diarrhea (2.4%) or unintentional weight loss (3.1%). In subjects with OH at enrollment, progressive increase in systolic and diastolic orthostatic difference was observed. OH was also associated with significantly worse quality of life. BP variability is a useful tool for assessing disease onset and severity in ATTR amyloidosis, particularly in patients with OH. Trial registration ClinicalTrials.gov : NCT00628745. • Orthostatic hypotension (OH) is an early symptom in ATTR amyloidosis. • Significantly worse quality of life was observed in patients with OH at enrollment. • Progressive increase in orthostatic differences was observed in patients with OH. • Changes in blood pressure can be a useful measure in ATTR amyloidosis. [ABSTRACT FROM AUTHOR]
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- 2019
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13. The demographic, genetic, and clinical characteristics of Latin American subjects enrolled in the Transthyretin Amyloidosis Outcomes Survey.
- Author
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Cruz, Márcia Waddington, Barroso, Fabio, González-Duarte, Alejandra, Mundayat, Rajiv, and Ong, Moh-Lim
- Subjects
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TRANSTHYRETIN , *AMYLOIDOSIS , *POLYNEUROPATHIES , *GENOTYPES , *DATA analysis - Published
- 2017
- Full Text
- View/download PDF
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