{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:41:51Z","timestamp":1790991711237,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (\n                      <jats:italic>p<\/jats:italic>\n                      =0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8,\n                      <jats:italic>p<\/jats:italic>\n                      =0.21).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-024-03198-7","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T05:02:40Z","timestamp":1715144560000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-4639","authenticated-orcid":false,"given":"Taha N.","family":"Qarni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe J. S.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Drachman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Khella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Pieretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas Sarmiento","family":"Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chafic","family":"Karam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"3198_CR1","doi-asserted-by":"publisher","unstructured":"Manganelli F, Fabrizi GM, Luigetti M, et al. Hereditary transthyretin amyloidosis overview. Neurological Sci. 2022;43. https:\/\/doi.org\/10.1007\/s10072-020-04889-2.","DOI":"10.1007\/s10072-020-04889-2"},{"key":"3198_CR2","unstructured":"Gertz MA. Hereditary ATTR amyloidosis: burden of illness and diagnostic challenges. Am J Manag Care. 2017;23:S107\u201312."},{"key":"3198_CR3","doi-asserted-by":"publisher","unstructured":"Luigetti M, Romano A, Di Paolantonio A, et al. Diagnosis and treatment of hereditary transthyretin amyloidosis (Hattr) polyneuropathy: Current perspectives on improving patient care. Ther Clin Risk Manag. 2020;16. https:\/\/doi.org\/10.2147\/TCRM.S219979.","DOI":"10.2147\/TCRM.S219979"},{"key":"3198_CR4","doi-asserted-by":"publisher","unstructured":"Hawkins PN, Ando Y, Dispenzeri A, et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47. https:\/\/doi.org\/10.3109\/07853890.2015.1068949.","DOI":"10.3109\/07853890.2015.1068949"},{"key":"3198_CR5","unstructured":"Ema. Assessment report Vyndaqel. Ema\/729083\/2011. 2011;44."},{"key":"3198_CR6","unstructured":"Danehy S. .S. FDA Approves VYNDAQEL\u00ae and VYNDAMAXTMfor Use in Patients with Transthyretin Amyloid Cardiomyopathy, a Rareand Fatal Disease. Business Wire. 2019."},{"key":"3198_CR7","doi-asserted-by":"publisher","unstructured":"Casta\u00f1o A, Helmke S, Alvarez J, et al. Diflunisal for ATTR Cardiac Amyloidosis. Congestive Heart Failure. 2012;18. doi: https:\/\/doi.org\/10.1111\/j.1751-7133.2012.00303.x.","DOI":"10.1111\/j.1751-7133.2012.00303.x"},{"key":"3198_CR8","doi-asserted-by":"publisher","unstructured":"Berk JL, Suhr OB, Obici L, et al. Repurposing diflunisal for familial amyloid polyneuropathy: A randomized clinical trial. JAMA. 2013;310. doi: https:\/\/doi.org\/10.1001\/jama.2013.283815.","DOI":"10.1001\/jama.2013.283815"},{"key":"3198_CR9","doi-asserted-by":"publisher","unstructured":"Miller SR, Sekijima Y, Kelly JW. Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Laboratory Investigation. 2004;84. doi: https:\/\/doi.org\/10.1038\/labinvest.3700059.","DOI":"10.1038\/labinvest.3700059"},{"key":"3198_CR10","doi-asserted-by":"publisher","unstructured":"Gertz MA, Mauermann ML, Grogan M, et al. Advances in the treatment of hereditary transthyretin amyloidosis: A review. Brain Behav. 2019;9. https:\/\/doi.org\/10.1002\/brb3.1371.","DOI":"10.1002\/brb3.1371"},{"key":"3198_CR11","doi-asserted-by":"publisher","unstructured":"Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. 2018;379. doi: https:\/\/doi.org\/10.1056\/nejmoa1716793.","DOI":"10.1056\/nejmoa1716793"},{"key":"3198_CR12","doi-asserted-by":"publisher","unstructured":"Adams D, Gonzalez-Duarte A, O\u2019Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. New England J Med. 2018;379. doi: https:\/\/doi.org\/10.1056\/nejmoa1716153.","DOI":"10.1056\/nejmoa1716153"},{"key":"3198_CR13","doi-asserted-by":"publisher","unstructured":"Solomon SD, Adams D, Kristen A, et al. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients with Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study. Circulation. 2019;139. doi: https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.118.035831.","DOI":"10.1161\/CIRCULATIONAHA.118.035831"},{"key":"3198_CR14","doi-asserted-by":"publisher","unstructured":"Dasgupta NR, Rissing SM, Smith J, et al. Inotersen therapy of transthyretin amyloid cardiomyopathy. Amyloid. 2020;27. doi: https:\/\/doi.org\/10.1080\/13506129.2019.1685487.","DOI":"10.1080\/13506129.2019.1685487"},{"key":"3198_CR15","doi-asserted-by":"publisher","unstructured":"Cu\u00e9llar Rodr\u00edguez S. Novel Drugs Recently Authorized by EMA and FDA (Q3, 2022). Anales de la Real Academia Nacional de Farmacia. 2022;88. doi: https:\/\/doi.org\/10.53519\/analesranf.2022.88.03.06.","DOI":"10.53519\/analesranf.2022.88.03.06"},{"key":"3198_CR16","doi-asserted-by":"publisher","unstructured":"von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370. doi: https:\/\/doi.org\/10.1016\/S0140-6736(07)61602-X.","DOI":"10.1016\/S0140-6736(07)61602-X"},{"key":"3198_CR17","doi-asserted-by":"publisher","unstructured":"Maurer MS, Hanna M, Grogan M, et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68. doi: https:\/\/doi.org\/10.1016\/j.jacc.2016.03.596.","DOI":"10.1016\/j.jacc.2016.03.596"},{"key":"3198_CR18","doi-asserted-by":"publisher","unstructured":"Kaku MC, Bhadola S, Berk JL, et al. Neurological manifestations of hereditary transthyretin amyloidosis: a focus on diagnostic delays. Amyloid. 2022;29. doi: https:\/\/doi.org\/10.1080\/13506129.2022.2046557.","DOI":"10.1080\/13506129.2022.2046557"},{"key":"3198_CR19","doi-asserted-by":"publisher","unstructured":"Sekijima Y, Tojo K, Morita H, et al. Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid. 2015;22. doi: https:\/\/doi.org\/10.3109\/13506129.2014.997872.","DOI":"10.3109\/13506129.2014.997872"},{"key":"3198_CR20","doi-asserted-by":"publisher","unstructured":"Falk RH, Haddad M, Walker CR, et al. Effect of Tafamidis on Serum Transthyretin Levels in Non-Trial Patients With Transthyretin Amyloid Cardiomyopathy. JACC CardioOncol. 2021;3. doi: https:\/\/doi.org\/10.1016\/j.jaccao.2021.08.007.","DOI":"10.1016\/j.jaccao.2021.08.007"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03198-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03198-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03198-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T05:05:57Z","timestamp":1715144757000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03198-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3198"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03198-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3221526\/v1","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]},"assertion":[{"value":"7 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the University of Pennsylvania Institutional Research Board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There were no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"191"}}