Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy

作者：Laura Obici, Senda Ajroud‐Driss, Kon‐Ping Lin, John L. Berk, Julian D. Gillmore, Parag Kale, Haruki Koike, David Danese, Emre Aldinc, Chongshu Chen, John Vest, David Adams, the HELIOS-A Collaborators Study Group, Jonas Wixner, Rolf Backlund, Björn Pilebro, Intissar Anan, Fredrik Edbom, Anna Ekman, Sandra Arvidsson, Ulrika H. Englund, Karin Söderberg, Erik Nordh, Erica Uneus, Kristin Samuelsson, A Nilzén, Rayomand Press, Mirjam Bilecen, Teresa Coelho, Marta Novais, Patrícia Rodrigues, Ana Silva, Inês Lopes Cardoso, Carla Rodrigues, Joana Ramalho, Helder Martins, Mónica G. Silva, Nádia Guimarães, Javier Martínez Pérez, Antonio Hipólito Reis, Julia R Monte, Natália Ferreira, Cristina Alves, Márcio Cardoso, Ricardo Cotrin Teixeira, Isabel Conceição, Filipa Lamas, Miguel Oliveira Santos, Catarina Falcão de Campos, Conceição de Azevedo Coutinho, José Castro, Isabel Castro, Daniela Rodrigues Silva, Susana Gonçalves, Eleonora Di Buduo, Claudia Sforzini, Roberta Mussinelli, Vittorio Rosti, Alessandro Lozza, Anna Racchi, Mario Sabatelli, Marco Luigetti, Giulia Bisogni, Ângela Romano, Valeria Guglielmino, Andrea Di Paolantonio, Daniela Bernardo, Giuseppe Vita, Anna Mazzeo, Massimo Russo, Davide Pareyson, Daniela Calabrese, Silvia Fenu, Paola Saveri, Hans Nienhuis, Geert Bokhorst, Carlien Roos, Margriet Couperus, Greetje de Jong, Anne F. Brunger, Gea Drost, Fiete Lange, Adinda Colauto, Márcia Waddington‐Cruz, Aline França de Abreu, Roberto Coury Pedrosa, Renata Gervais de Santa Rosa, Moisés Dias, Fetra Rakotondratafika, Andoni Echaniz‐Laguna, Cécile Cauquil, Céline Labeyrie, Guillemette Beaudonnet, Yasmine Boubrit, Amina Gaouar, Halima Bourenane, Shahram Attarian, El Khansa Yahia, Annie Verschueren, Aude‐Marie Grapperon, Émilien Delmont, Violaine Planté‐Bordeneuve, Laetitia Vervoitte, Samar S. Ayache, Philippe Le Corvoisier, Raphaele Arrouasse, Thierry Gendre, Laure Abou Chakra, Cécile Focseneanu, Caroline Barau, Guilhem Solé, L. Belin, Marie Helene Violleau, Fanny Duval-Bontemps, Rami Massie, Xin Dong, Francisco Muñoz-Beamud, Sandra García, Cristina Borrachero, Álvaro Gragera Martínez, Lucía Galán Dávila, Marta Palacios, Laura Martínez Vicente, Leopoldo Pérez de Isla, Carlos Casasnovas, Carles Díez‐López, Elena Muñoz Fabra, José González‐Costello, Sonia Guerrero, Sergi Yun Viladomat, Yurema Martinez, Valentina Vélez-Santamaría, Velina Nedkova-Hristova, Pablo García Pavía, Ariadna González Segovia, Fernando de Frutos, Esther González-López, Fernándo Domínguez, Luis Escobar-López, Eva Cabrera-Romero, Paula Sánchez Gismera, María de la Iglesia, Fernando Martinez Valle, G Aguila, Karen Lorite, N. Raguer, Pilar Suñé, P Piera, Carlos Ortega, Carla Aguilar, Gisela Gili, Hartmut Schmidt, Christel Langenstroer, Anna Hüsing‐Kabar, Iyad Kabar, Matthias Schilling, Frauke Friebel, Phil‐Robin Tepasse, Frank Birklein, Monika Firros, Fabiola Escolano‐Lozano, Caitlin Brueckner, Vanessa Bahnam, Michelle Kaku, K. H. Vincent Lau, Janice F. Wiesman, Martha Grogan, Susanna Miller, Janell Grazzini Frantz, Diane C. Schmidt, Omar F. AbouEzzeddine, Wayne H. Miller, Grace Lin, Morie A. Gertz, Angela Dispenzieri, Thomas H. Brannagan, Raisy Fayerman, Elizabeth DuVerger, Jorge Cabrera, Mathew S. Maurer, Christina Ulane, Louis H. Weimer, Stephen H. Tsang, Jeffrey Shije, Nathan Carberry, Sai Si Thu, Dianna Quan, Brianna Blume, J. Scott Overcash, Pu He, Kia Lee, Hanh Chu, Karla Zepeda, Michael R. Waters, Thao Vuong, Derya J Coskun, Kimberly Quillin, Allison Davis, Michael Polydefkis, Jing Ye, Xiaoling Li, Mohammad Khoshnoodi, Geno Vista, Tae Chung, Michele Watt, Dan Tsottles, Ahmad Masri, Dayna Carlson, Brian Drachman, Patricia Divito, Hansie Mathelier, Margaret Shanks, Karen Maslowski, Sami Khella, J. Pieretti, Benjamin Joslin, Emma Schmidt, Miriam Freimer, Julie Agriesti, Fábio Barroso, F Picone, Andrea Lautre, Lucas Orellana, Wenqin Du, Joost Felius, Alejandra González‐Duarte, Karla Cárdenas‐Soto, Rebecca Traub, Manisha Chopra, Chi‐Chao Chao, Chia-Hua Hsu, Li‐Kai Tsai, Ming‐Jen Lee, Jen-Jen Su, Sung‐Tsang Hsieh, Hsueh‐Wen Hsueh, Hsi-Chieh Chou, Byoung‐Joon Kim, Hyesun Kang, Ju‐Hong Min, Eun‐Seok Jeon, Yeon Hak Chung, Jae Hong Park, Jeeyoung Oh, Hyun Joo Jeong, Ivailo Tournev, Sashka Zhelyazkova, Yohei Misumi, Yumiko Sakamoto, Nami Hashimoto, Yoshimi Misumi, Aya Takahashi, Mitsuharu Ueda, Teruaki Masuda, Akihiko Ueda, Masahisa Katsuno, Kazuki Tajima, Momoko Sumi, Fujiko Hasegawa, Takahiro Okumura, Masahiro Iijima, Yuki Fukami, Daisuke Ito, Yoshiyuki Kishimoto, Tomoyuki Kazuta, Katsuhiko Kato, Naohiro Mouri, Soma Furukawa, Ryoji Nishi, Yoshiki Sekijima, Keiko Ito, Naga-aki Kato, Dai Kishida, Hideki Mochizuki, Kaori Okada, Kurumi Ohashi, Kensuke Ikenaka, Masayuki Nakamori, Makoto Kinoshita, Bella Ruth R. Mapalo, Steven Law, Liza Chacko, Helen J. Lachmann, Oliver Cohen, Yousuf Razvi, Sindhu Varughese, Ana Martinez–Naharro, Richard W. Orrell, Marianna Fontana, Lisa Rannigan, Sarah Louth, Eleni Zamba‐Papanicolaou, Demetra Charalamnibous, Rana Abu Manneh, Kleopas A. Kleopa, Theodoros Christodoulides, Savvas Frangos, Michele Galganski-Cleanthous, E Gaglia, Irene Smoleski, Elena Kkolou, Andry Ploutarchou, Mariana Hanghiuc, Galini Chroidou, Olga Stylianou, Anastasia Krokou, Irene Zannetou, Efstathios Kastritis, Dimitra Papadopoulou, Ilias Spinasas, Panayiotis Bakalis, Nikolaos Kanellias, Despoina Fotiou, Ioanna Dialoupi, Magdalini Migko, Maria Gavriatopoulou, Soon-Chai Low, Mark Taylor, Graeme J. Stewart, Helen Knight, Steve Vucic, Antonia Carroll, Matthew Silsby, Dan Suan, Simon Gibbs, Carmela Corfield, Suzana Jakicic, Hayden Jina, Stephen B. Ting, Shi Qin Wong, Peter Mollee, Lynda McKinley, Emad Abro, Dariusz Korczyk, Gauthier Remiche, Nick Alaerts, Fabienne De Veylder, Kristl G. Claeys, E. Debien, Joyce Cremers, Ann D’Hondt, Bram De Wel · 发表于：Neurology and Therapy · 年份：2023 · DOI：10.1007/s40120-023-00522-4 · 被引用次数：21 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Alzheimer's disease research and treatments、Skin and Cellular Biology Research

Hereditary 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. The 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. At 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 modifie...