Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

作者：Renato Mantegazza, Gil I. Wolfe, Srikanth Muppidi, Heinz Wiendl, Kenji P. Fujita, Fanny O’Brien, Heather Booth, James F. Howard, Claudio Gabriel Mazia, Miguel Wilken, Fabio Adrian Barroso, Juliet Saba, Marcelo Francisco Rugiero, Mariela Bettini, Marcelo Chaves, Gonzalo Vidal, Alejandra Dalila Garcia, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy Mercelis, Délphine Mahieu, Linda Wagemaekers, Philip Van Damme, Annelies Depreitere, Caroline Schotte, Charlotte Smetcoren, Olivier Stevens, Sien Van Daele, Nicolas Vandenbussche, Annelies Vanhee, Sarah Verjans, Jan Vynckier, Ann D’Hont, Petra Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Gabor Lovasamela César, Ana Paula Souto Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Silva Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Maria da Penha Ananias Morita, Érica Nogueira Coelho, Gabriel Pina Paiva, M Tovar Pozo, Natália Prando, Debora Dada Martineli Torres, Cristiani Fernanda Butinhao, Gustavo Duran, Tomás Augusto Suriane Fialho, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Luciana Renata Cubas Volpe, Luciana Souza Duca, Maurício AndréGheller Friedrich, Alexandre Guerreiro, Alexandre Guerreiro, Henrique Mohr, Maurer Pereira Martins, Daiane da Cruz Pacheco, Luciana Ferreira, Ana Paula Macagnan, Graziela Hünning Pinto, Aline de Cassia Santos, Acary Souza Bullé Oliveira, Ana Carolina Amaral de Andrade, Marcelo Annes, Liene Duarte Silva, Valéria Cavalcante Lino, Wladimir Bocca Vieira de Rezende Pinto, Natália Assis, Fernanda Carrara, Carolina Miranda, Iandra Souza, Patrícia Fernandes, Zaeem Azfer Siddiqi, Cecile L. Phan, Jeffrey Narayan, Derrick Blackmore, Ashley Mallon, Rikki Roderus, Elizabeth Watt, Stanislav Voháňka, Josef Bednařík, Magda Chmelikova, Marek Čierny, Stanislava Toncrova, Jana Junkerová, Barbora Kurková, Katarína Reguliová, Olga Zapletalová, Jiří Piťha, Iveta Nováková, Michaela Týblová, Ivana Jurajdova, Marcela Wolfova, Henning Andersen, Thomas Harbo, Lotte Vinge, Susanne Krogh, Anita Mogensen, John Vissing, Joan L Sunnleyg Højgaard, Nanna Witting, Anne Mette Ostergaard Autzen, Jane Pedersen, Juha-Pekka Erälinna, Mikko Laaksonen, Olli Oksaranta, Tuula Harrison, Jaana Eriksson, Csilla Rózsa, Melinda Horvath, Gábor Lovas, Judit Matolcsi, Gedeonne Jakab, Györgyi Szabó, Gedeonne Jakab, Brigitta Szabadosne, László Vécsei, Lívia Dézsi, Edina Tímea Varga, Monika Konyane, Giovanni Antonini, Antonella Di Pasquale, Matteo Garibaldi, Stefania Morino, Fernanda Troili, Laura Fionda, Antonella Di Pasquale, Amelia Evoli, Paolo Emilio Alboini, Valentina Damato, Raffaele Federico Iorio, Maurizio Inghilleri, Laura Fionda, Vittorio Frasca, Elena Giacomelli, Maria Cristina Gori, Diego Lopergolo, Emanuela Onesti, Vittorio Frasca, Maria Gabriele, Francesco Saccà, Alessandro Filla, Teresa Costabile, Enrico Marano, Angiola Maria Fasanaro, Angela Marsili, Giorgia Puorro, Carlo Giuseppe Antozzi, Silvia Bonanno, Giorgia Camera, Alberta Locatelli, Lorenzo Maggi, Maria Barbara Pasanisi, Angela Campanella, Akiyuki Uzawa, Tetsuya Kanai, Naoki Kawaguchi, Masahiro Mori, Yoko S. Kaneko, Akiko Kanzaki, Eri Kobayashi, Hiroyuki Murai, Katsuhisa Masaki, Dai Matsuse, Takuya Matsushita, Taira Uehara, Misa Shimpo, Maki Jingu, Keiko Kikutake, Yumiko Nakamura, Yoshiko Sano, Kimiaki Utsugisawa, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Makoto Samukawa, Hidekazu Suzuki, Miyuki Morikawa, Sachiko Kamakura, Eriko Miyawaki, Meinoshin Okumura, Soichiro Funaka, Tomohiro Kawamura, Masayuki Nakamori, Masanori P. Takahashi, Namie Taichi, Tomoya Hasuike, Eriko Higuchi, Hisako Kobayashi, Kaori Osakada, Hirokazu Shiraishi, Teiichiro Miyazaki, Masakatsu Motomura, Akihiro Mukaino, Shunsuke Yoshimura, Shizuka Asada, Seiko Yoshida, Shoko Amamoto, Tomomi Kobashikawa, Megumi Koga, Maeda Yasuko, Kazumi Takada, Mihoko Takada, Masako Tsurumaru, Yumi Yamashita, Yasushi A. Suzuki, Tetsuya Akiyama, Koichi Narikawa, Ohito Tano, Kenichi Tsukita, Rikako Kurihara, Fumie Meguro, Yusuke Fukuda, Miwako Sato, Tomihiro Imai, Emiko Tsuda, Shun Shimohama, Takashi Hayashi, Shin Hisahara, Tomihiro Imai, Jun Kawamata, Takashi Murahara, Masaki Saitoh, Shun Shimohama, Shu-Ichiro Suzuki, Daisuke Yamamoto, Yoko Ishiyama, Naoko Ishiyama, Mayuko Noshiro, Rumi Takeyama, Kaori Uwasa, Ikuko Yasuda, Anneke J. van der Kooi, Marianne de Visser, Tamar Gibson, Byung‐Jo Kim, Chang Nyoung Lee, Yong Seo Koo, Hung Youl Seok, Hoo Nam Kang, HyeJin Ra, Byoung Joon Kim, Eun Bin Cho, Misong Choi, HyeLim Lee, Ju‐Hong Min, Jinmyoung Seok, JiEun Lee, Da Yoon Koh, Juyoung Kwon, SangAe Park, Eun Haw Choi, Yoon‐Ho Hong, Sohyun Ahn, Dae Lim Koo, Jae‐Sung Lim, Chaewon Shin, Ji Ye Hwang, Miri Kim, Seung Min Kim, Ha-Neul Jeong, JinWoo Jung, Yool-hee Kim, Hyung‐Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju Shin, Carlos Casasnovas, Maria Antònia Albertí Aguiló, Christian Homedes-Pedret, Natalia Juliá Palacios, Laura Diez Porras, Valentina Vélez-Santamaría, Ana María Pello Lázaro, Josep Gámez Carbonell, Pilar Suñé, Maria Salvadó Figueras, Gisela Gili, Gonzalo Mazuela, Isabel Illa, Elena Cortés Vicente, Jordi Díaz‐Manera, Luis Antonio Querol Gutiérrez, Ricardo Rojas Garcia, Núria Vidal, Elisabet Arribas-Ibar, Exuperio Díez‐Tejedor, Pilar Gomez Salcedo, Mireya Fernández-Fournier, Pedro Lopez Ruiz, Francisco Javier Rodríguez de Rivera Garrido, Mireya Fernández-Fournier, María Sastre, Fredrik Piehl, Albert Hietala, Lena Bjarbo, İhsan Şükrü Şengün, Arzu Meherremova, Pınar Özçelik, Bengu Balkan, Celal Tuga, Müzeyyen Ugur, Sevim Erdem‐Özdamar, Can Ebru Bekircan‐Kurt, Nazire Pınar Acar, Ezgi Yılmaz, Yagmur Caliskan, Gulsah Orsel, Hüsnü Efendi, Seda Aydinlik, Hakan Çavuş, Ayşe Kutlu, Gulsah Becerikli, Cansu Semiz, Ozlem Tun, Murat Terzi, Baki Doğan, Musa Kazım Onar, Sedat Şen, Tugce Kirbas Cavdar, Adife Veske, Fiona Norwood, Aikaterini Dimitriou, Jakit Gollogly, Mohamed Mahdi‐Rogers, Arshira Seddigh, Giannis Sokratous, Gal Maier, Faisal Sohail, Saiju Jacob, Girija Sadalage, Pravin Torane, Pravin Torane, Claire Brown, Amna Yousaf Shah, Sivakumar Sathasivam, Heike Arndt, Debbie Davies, Dave Watling, Anthony A. Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine R. Amato, Shirli Toska, Nicholas J. Silvestri, Kara Patrick, Karen Zakalik, Jonathan Katz, Robert G. Miller, Marguerite Engel, Dallas A. Forshew, Elena K. Bravver, Benjamin Brooks, Mohammed Sanjak, Sarah Plevka, Maryanne Burdette, Scott Gordon Cunningham, Megan Kramer, Joanne Nemeth, Clara Schommer, Scott Tierney, Vern C. Juel, Jeffrey T. Guptill, Lisa D. Hobson‐Webb, Janice M. Massey, Kate Beck, Donna Carnes, John Loor, Amanda Anderson, Robert M. Pascuzzi, Cynthia L. Bodkin, John Kincaid, Riley Snook, Sandra Guingrich, Angela Micheels, Vinay Chaudhry, Andrea M. Corse, Betsy Mosmiller, Andrea A. Kelley, Doreen T. Ho, Jayashri Srinivasan, Michal Vytopil, Jordan Jara, Nicholas Ventura, Cynthia Carter, Craig Donahue, Carol Herbert, Stephanie Scala, Elaine Weiner, Sharmeen Alam, Jonathan McKinnon, Laura Haar, Naya McKinnon, Karan Alcon, Kaitlyn McKenna, Nadia Sattar, Kevin Daniels, Dennis Jeffery, Miriam L. Freimer, Joseph Chad Hoyle, John T. Kissel, Julie Agriesti, Sharon Chelnick, Louisa S. Mezache, Colleen A. Pineda, Filiz Muharrem, Chafic Karam, Julie A. Khoury, Tessa Marburger, Harpreet Kaur, Diana Dimitrova, James M. Gilchrist, Brajesh Agrawal, Mona Elsayed, Stephanie Kohlrus, Angela Ardoin, Taylor Darnell, Laura R. Golden, Barbara Lokaitis, J. D. Seelbach, Neelam Goyal, Sarada Sakamuri, Yuen T. So, Shirley Paulose, Sabrina Pol, Lesly Welsh, Ratna K. Bhavaraju-Sanka, Alejandro Tobon Gonzalez, Lorraine Dishman, Floyd Jones, Anna González, Patricia Padilla, Amy R. Saklad, Marcela Silva, Sharon Nations, Jaya R. Trivedi, Steve Hopkins, Mohamed Kazamel, Mohammad Alsharabati, Lu Hong Liang, Kenkichi Nozaki, Sandi Mumfrey-Thomas, Amy Woodall, Tahseen Mozaffar, Tiyonnoh Cash, Namita Goyal, Gulmohor Roy, Veena Mathew, Fatima Maqsood, Brian Minton, Helen Jones, Jeffrey Rosenfeld, Rebekah Garcia, Laura Echevarria, Sonia García, Michael Pulley, Shachie Aranke, Alan Ross Berger, Jaimin Shah, Yasmeen Shabbir, Lisa S. Smith, Mary E. Varghese, Yasmeen Shabbir, Laurie Gutmann, Ludwig Gutmann, Nivedita U. Jerath, Christopher S. Nance, Andrea Swenson, Heena M. Olalde, Nicole Kressin, Jeri Sieren, Richard J. Barohn, Mazen M. Dimachkie, Melanie D. Glenn, April McVey, Mamatha Pasnoor, Jeffrey M. Statland, Yunxia Wang, Tina Liu, Kelley Emmons, Nicole Jenci, Jerry Locheke, Alex Fondaw, Kathryn Johns, Gabrielle Rico, Maureen Walsh, Laura L. Herbelin, Charlene E. Hafer‐Macko, Justin Y. Kwan, Lindsay A. Zilliox, Karen Callison, Valerie Young, Beth DiSanzo, Kerry Naunton, Michael G Benatar, Martin Bilsker, Khema Ram Sharma, Anne E. Cooley, Eliana Reyes, Sara-Claude Michon, Danielle Sheldon, Julie Steele, Chafic Karam, Rebecca Traub, Manisha Chopra, Tuan Vu, Lara W. Katzin, Terry McClain, Brittany E. Harvey, Adam Hart, Kristin Huynh, Said R. Beydoun, Amaiak Chilingaryan, Victor Doan, Brian S. Droker, Hui Gong, Sanaz Karimi, Frank Y. H. Lin, Terry McClain, Krishna Polaka, Akshay Shah, Anh Thu Tran, Salma Akhter, Ali Malekniazi, Rup Tandan, Michael K. Hehir, Waqar Waheed, S. Deborah Lucy, Michael D. Weiss, Jane Distad, Susan Strom, Sharon Downing, Bryan Inho Kim, Tulio E. Bertorini, Thomas D. Arnold, Kendrick Henderson, Rekha Pillai, Ye Liu, Lauren Wheeler, Jasmine Hewlett, Mollie Vanderhook, Richard J. Nowak, Daniel B. DiCapua, Benison Keung, Aditya Kumar, Huned S. Patwa, Kimberly R. Robeson, Irene Hwa Yang, Joan L. Nye, Hong Vu · 发表于：Neurology · 年份：2020 · DOI：10.1212/wnl.0000000000011207 · 被引用次数：82 · 研究领域：Myasthenia Gravis and Thymoma、Coagulation, Bradykinin, Polyphosphates, and Angioedema、Adrenal Hormones and Disorders

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings sup...