Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy

作者：David Adams, Jonas Wixner, Michael Polydefkis, John L. Berk, Isabel Conceição, Angela Dispenzieri, Amanda Peltier, Mitsuharu Ueda, Shaun Bender, Kelley E. Capocelli, Patrick Y. Jay, Elena Yureneva, Laura Obici, patisiran Global OLE study group, Giuseppe Vita, Vincenzo Rizzo, Massimo Russo, Anna Mazzeo, Luca Gentile, John L. Berk, Janice F. Wiesman, Michelle Kaku, Vincent Lau, Douglas DeLong, James A. R. Dalton, John J. May, Shahram Attarian, Émilien Delmont, Jean Pouget, Annie Verschueren, Aude‐Marie Grapperon, Emmanuelle Campana-Salort, Isabel Conceição, Carlos Marques‐Neves, Miguel Oliveira Santos, Conceição de Azevedo Coutinho, Catarina Falcão de Campos, Teresa Coelho, Antonio Hipólito Reis, Nuno Correia, Javier Martínez Pérez, Ana Martins da Silva, Cristina Alves, Márcio Cardoso, Kátia Valdrez, Julia R Monte, Marta Novais, Nádia Guimarães, Inês Cardoso, Mónica Freitas, Joana Ramalho, Natália Ferreira, Daisuke Kuzume, Masahiro Yamasaki, Yuko Morimoto, Céline Tard, É. Hachulla, Clément Gauvain, Maria-Claire Migaud-Chervy, Dominique Deplanque, Elsa Jozefowicz, Loïc Lebellec, David Adams, Marie Théaudin-Saliou, Cécile Cauquil-Michon, Céline Labeyrie, Adeline Not, Abdallah Al‐Salameh, Anne-Lise Lecoq, Maeva Stephant, Andoni Echaniz‐Laguna, Laurent Becquemont, Guillemette Beaudonnet, Vincent Algalarrondo, Ludivine Eliahou, Michel Slama, Antoine Rousseau, Aïssatou Signaté, Paola Darche, Jérôme Grimaud, Emeline Berthelot, Jocelyn Inamo, Violaine Planté‐Bordeneuve, Thierry Gendre, Raphaele Arrouasse, Samar S. Ayache, Laura Ernande, Philippe Le Corvoisier, Hayet Salhi, Ariane Choumert, Cyril Charlin, Thomas Megelin, Thomas H. Brannagan, Steven Tsang, Fernanda Wajnsztajn, Jeffrey Shije, Christina Ulane, Inna Kleyman, Louis H. Weimer, Comana Cioroiu, Kleopas A. Kleopa, Eleni Zamba‐Papanicolaou, Satoshi Tada, Masahiro Nagai, Rina Ando, Yuki Yamanishi, J. Scott Overcash, Sinikka Green, Michael R. Waters, Derya J Coskun, Paul S. Manos, Karla A Zepeda, William O’Riordan, Laura Obici, Andrea Cortese, Alessandro Lozza, Giampaolo Merlini, Vittorio Rosti, Mario Sabatelli, Giulia Bisogni, Daniela Bernardo, Marco Luigetti, Andrea Di Paolantonio, Valeria Guglielmino, Ângela Romano, Hans Nienhuis, Arnt V. Kristen, Christian Nagel, Fabian aus dem Siepen, Selina Hein, Shuichiro Neshige, Josep M. Campistol, Lida María Rodas Marín, Josep Miquel Blasco Pelicano, Lucía Galán Dávila, Vanesa Pytel Cordoba, A. Guerrero Sola, Alejandro Horga, Julián García Feijoo, Leopoldo Pérez de Isla, Wilson Marques, Carolina Lavigne Moreira, Vanessa Daccach Marques, Francisco Muñoz Beamud, Cristina Borrachero, Iván A. López, Mónica Sanz, E Oliver, Juan González Moreno, J. Michael Martinez, Cristina Descals, Mercedes Usón, Francisco Jose Vega, Antoni Figuerola, Carles Montalà, Márcia Waddington‐Cruz, Aline França de Abreu, Moises Dias da Silva, Renata Gervais de Santa Rosa, Marcus Vinícius Pinto, Amanda Cardoso Berensztejn, Luiz Felipe Pinto, Mariana de Andrade Guedes, Fábio Barroso, Andrea Lautre, Lucas Orellana, Maria Alejandra González-Duarte Briseño, Karla Cárdenas‐Soto, Carlos Cantú‐Brito, David Rivera de la Parra, Jose Pablo Hernandez Reyes, Maria del Mar Saniger Alba, Yeşim Parman, Erdi Şahin, Nail Güven Serbest, Hacer Durmuş, Arman Çakar, Saçit Karamürsel, Ali Elitok, Nermin G Sirin Inan, Emre Altinkurt, Michael Polydefkis, Adriane C Allen, Vinay Chaudhry, R. J. Jarrett, Neil M. Bressler, Mandeep Singh, Mohammad Khoshnoodi, Daniel P. Judge, Alvin T Lui, Tae Chung, Geno Vista, Syed Mahmood Shah, Hirotoshi Hamaguchi, Tetsuya Oda, Masahiro Shimomura, Christof Scheid, Udo Holtick, Jeeyoung Oh, Hee Jin Kim, Hyun Jin Shin, Kyomin Choi, Mitsuharu Ueda, Yohei Misumi, Toshiya Nomura, Takahisa Tateishi, Elizabeth A. Mauricio, Elliot L. Dimberg, Leslie T. Cooper, Angela Dispenzieri, Amie Fonder, Miriam Hobbs, P. James B. Dyck, Wilson I. Gonsalves, Nelson Leung, Thomas E. Witzig, Yi L. Hwa, Prashant Kapoor, Shaji Kumar, Yi Lin, S. Vincent Rajkumar, David Dingli, Morie A. Gertz, P. James B. Dyck, Linde E. Gove, Samir Dalia, David Croy, Tim Holding, Peter D. Gorevic, Chi‐Chao Chao, Ming‐Jen Lee, Jen-Jen Su, Sung‐Tsang Hsieh, Li‐Kai Tsai, Shin‐Joe Yeh, Chih‐Chao Yang, Chao-Wen Lin, Senda Ajroud‐Driss, Robert Sufit, John-Michael Li, Miriam Freimer, Samantha LoRusso, Yasuhiro Aso, Byoung‐Joon Kim, JuHyeon Kim, Ga-Yeon Lee, Eun Bin Cho, Eun‐Seok Jeon, Ju‐Hong Min, Jin Myoung Seok, Hye Lim Lee, Jae Hong Park, Yoshiki Sekijima, Naga-aki Kato, Dai Kishida, Akiyo Hineno, Minori Kodaira, Tsuneaki Yoshinaga, Ken Takasone, Teruyoshi Miyahara, Yusuke Takahashi, Akira Imai, Kazuhiko Matsumoto, Kon-Ping Lin, Yi‐Chung Lee, Jonas Wixner, Björn Pilebro, Ole B. Suhr, Intissar Anan, Erik Nordh, Fátima Pedrosa Domellöf, Maria Chermenina, Anneli Nygren, Ivaylo Tournev, Sashka Zhelyazkova, Zheyna Cherneva, S. Sarafov, Teodora Chamova, Sylvia Cherninkova-Gopina, Hartmut Schmidt, Elena Vorona, Anna Huesing-Kabar, Matthias Schilling, Iyad Kabar, Phil‐Robin Tepasse, Julian D. Gillmore, Ana Martinez–Naharro, Liza Chacko, Oliver Cohen, Steven Law, Tamer Rezk, Helen J. Lachmann, Dianna Quan, Stacy Dixon, Vera Fridman, Soon-Chai Low, Khean Jin Goh, Michelle M. Mezei, Kristin Jack, N. Kevin Wade, Glenn Lopate, Stephanie Geisler, R. Brian Sommerville, Julaine Florence, Graeme J. Stewart, Mark Taylor, Daniel Suan · 发表于：JAMA Neurology · 年份：2025 · DOI：10.1001/jamaneurol.2024.4631 · 被引用次数：34 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Alzheimer's disease research and treatments、Parathyroid Disorders and Treatments

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants: This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention: Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures: Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results: At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completin...