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 support the use of eculizumab in this previously difficult-to-treat patient population. Clinicaltrialsgov identifier: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. Classification of evidence: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.
Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension / Renato, Mantegazza; Gil I, Wolfe; Srikanth, Muppidi; Heinz, Wiendl; Kenji P, Fujita; Fanny L, O'Brien; Heather D E, Booth; Howard, ; F, James; Gabriel Mazia, Claudio; Wilken, Miguel; Barroso, Fabio; Saba, Juliet; Rugiero, Marcelo; Bettini, Mariela; Chaves, Marcelo; Vidal, Gonzalo; Dalila Garcia, Alejandra; De Bleecker, Jan; Van den Abeele, Guy; de Koning, Kathy; De Mey, Katrien; Mercelis, Rudy; Mahieu, Délphine; Wagemaekers, Linda; Van Damme, Philip; Depreitere, Annelies; Schotte, Caroline; Smetcoren, Charlotte; Stevens, Olivier; Van Daele, Sien; Vandenbussche, Nicolas; Vanhee, Annelies; Verjans, Sarah; Vynckier, Jan; D'Hont, Ann; Tilkin, Petra; Alves de Siqueira Carvalho, Alzira; Dias Brockhausen, Igor; Feder, David; Ambrosio, Daniel; Lovasamela César, Gabor; Paula Melo, Ana; Martins Ribeiro, Renata; Rocha, Rosana; Bezerra Rosa, Bruno; Veiga, Thabata; Augusto da Silva, Luiz; Santos Engel, Murilo; Gonçalves Geraldo, Jordana; da Penha Ananias Morita, Maria; Nogueira Coelho, Erica; Paiva, Gabriel; Pozo, Marina; Prando, Natalia; Dada Martineli Torres, Debora; Fernanda Butinhao, Cristiani; Duran, Gustavo; Augusto Suriane Fialho, Tomás; Cristina Gomes da Silva, Tamires; Otavio Maia Gonçalves, Luiz; Eduardo Pazetto, Lucas; Renata Cubas Volpe, Luciana; Souza Duca, Luciana; AndréGheller Friedrich, Maurício; Guerreiro, Alexandre; Guerreiro, Alexandre; Mohr, Henrique; Pereira Martins, Maurer; da Cruz Pacheco, Daiane; Ferreira, Luciana; Paula Macagnan, Ana; Pinto, Graziela; de Cassia Santos, Aline; Souza Bulle Oliveira, Acary; Carolina Amaral de Andrade, Ana; Annes, Marcelo; Duarte Silva, Liene; Cavalcante Lino, Valeria; Pinto, Wladimir; Assis, Natália; Carrara, Fernanda; Miranda, Carolina; Souza, Iandra; Fernandes, Patrícia; Siddiqi, Zaeem; Phan, Cecile; Narayan, Jeffrey; Blackmore, Derrick; Mallon, Ashley; Roderus, Rikki; Watt, Elizabeth; Vohanka, Stanislav; Bednarik, Josef; Chmelikova, Magda; Cierny, Marek; Toncrova, Stanislava; Junkerova, Jana; Kurkova, Barbora; Reguliova, Katarina; Zapletalova, Olga; Pitha, Jiri; Novakova, Iveta; Tyblova, Michaela; Jurajdova, Ivana; Wolfova, Marcela; Andersen, Henning; Harbo, Thomas; Vinge, Lotte; Krogh, Susanne; Mogensen, Anita; Vissing, John; Højgaard, Joan; Witting, Nanna; Mette Ostergaard Autzen, Anne; Pedersen, Jane; Erälinna, Juha-Pekka; Laaksonen, Mikko; Oksaranta, Olli; Harrison, Tuula; Eriksson, Jaana; Rozsa, Csilla; Horvath, Melinda; Lovas, Gabor; Matolcsi, Judit; Jakab, Gedeonne; Szabo, Gyorgyi; Jakab, Gedeonne; Szabadosne, Brigitta; Vecsei, Laszlo; Dezsi, Livia; Varga, Edina; Konyane, Monika; Antonini, Giovanni; Di Pasquale, Antonella; Garibaldi, Matteo; Morino, Stefania; Troili, Fernanda; Fionda, Laura; Di Pasquale, Antonella; Evoli, Amelia; Emilio Alboini, Paolo; D'Amato, Valentina; Iorio, Raffaele; Inghilleri, Maurizio; Fionda, Laura; Frasca, Vittorio; Giacomelli, Elena; Gori, Maria; Lopergolo, Diego; Onesti, Emanuela; Frasca, Vittorio; Gabriele, Maria; Sacca, Francesco; Filla, Alessandro; Costabile, Teresa; Marano, Enrico; Fasanaro, Angiola; Marsili, Angela; Puorro, Giorgia; Antozzi, Carlo; Bonanno, Silvia; Camera, Giorgia; Locatelli, Alberta; Maggi, Lorenzo; Pasanisi, Maria; Campanella, Angela; Uzawa, Akiyuki; Kanai, Tetsuya; Kawaguchi, Naoki; Mori, Masahiro; Kaneko, Yoko; Kanzaki, Akiko; Kobayashi, Eri; Murai, Hiroyuki; Masaki, Katsuhisa; Matsuse, Dai; Matsushita, Takuya; Uehara, Taira; Shimpo, Misa; Jingu, Maki; Kikutake, Keiko; Nakamura, Yumiko; Sano, Yoshiko; Utsugisawa, Kimiaki; Nagane, Yuriko; Kamegamori, Ikuko; Tsuda, Tomoko; Fujii, Yuko; Futono, Kazumi; Ozawa, Yukiko; Mizugami, Aya; Saito, Yuka; Samukawa, Makoto; Suzuki, Hidekazu; Morikawa, Miyuki; Kamakura, Sachiko; Miyawaki, Eriko; Okumura, Meinoshin; Funaka, Soichiro; Kawamura, Tomohiro; Nakamori, Masayuki; Takahashi, Masanori; Taichi, Namie; Hasuike, Tomoya; Higuchi, Eriko; Kobayashi, Hisako; Osakada, Kaori; Shiraishi, Hirokazu; Miyazaki, Teiichiro; Motomura, Masakatsu; Mukaino, Akihiro; Yoshimura, Shunsuke; Asada, Shizuka; Yoshida, Seiko; Amamoto, Shoko; Kobashikawa, Tomomi; Koga, Megumi; Yasuko, Maeda; Takada, Kazumi; Takada, Mihoko; Tsurumaru, Masako; Yamashita, Yumi; Suzuki, Yasushi; Akiyama, Tetsuya; Narikawa, Koichi; Tano, Ohito; Tsukita, Kenichi; Kurihara, Rikako; Meguro, Fumie; Fukuda, Yusuke; Sato, Miwako; Imai, Tomihiro; Tsuda, Emiko; Shimohama, Shun; Hayashi, Takashi; Hisahara, Shin; Imai, Tomihiro; Kawamata, Jun; Murahara, Takashi; Saitoh, Masaki; Shimohama, Shun; Suzuki, Shuichiro; Yamamoto, Daisuke; Ishiyama, Yoko; Ishiyama, Naoko; Noshiro, Mayuko; Takeyama, Rumi; Uwasa, Kaori; Yasuda, Ikuko; van der Kooi, Anneke; de Visser, Marianne; Gibson, Tamar; Kim, Byung-Jo; Nyoung Lee, Chang; Seo Koo, Yong; Youl Seok, Hung; Nam Kang, Hoo; Ra, Hyejin; Joon Kim, Byoung; Bin Cho, Eun; Choi, Misong; Lee, Hyelim; Min, Ju-Hong; Seok, Jinmyoung; Lee, Jieun; Yoon Koh, Da; Kwon, Juyoung; Park, Sangae; Haw Choi, Eun; Hong, Yoon-Ho; Ahn, So-Hyun; Lim Koo, Dae; Lim, Jae-Sung; Won Shin, Chae; Ye Hwang, Ji; Kim, Miri; Min Kim, Seung; Jeong, Ha-Neul; Jung, Jinwoo; Kim, Yool-Hee; Seok Lee, Hyung; Young Shin, Ha; Bi Hwang, Eun; Shin, Miju; Casasnovas, Carlos; Antonia Alberti Aguilo, Maria; Homedes-Pedret, Christian; Julia Palacios, Natalia; Diez Porras, Laura; Velez Santamaria, Valentina; Lazaro, Ana; Gamez Carbonell, Josep; Sune, Pilar; Salvado Figueras, Maria; Gili, Gisela; Mazuela, Gonzalo; Illa, Isabel; Cortes Vicente, Elena; Diaz-Manera, Jordi; Antonio Querol Gutiérrez, Luis; Rojas Garcia, Ricardo; Vidal, Nuria; Arribas-Ibar, Elisabet; Diez Tejedor, Exuperio; Gomez Salcedo, Pilar; Fernandez-Fournier, Mireya; Lopez Ruiz, Pedro; Javier Rodriguez de Rivera, Francisco; Fernandez-Fournier, Mireya; Sastre, Maria; Piehl, Fredrik; Hietala, Albert; Bjarbo, Lena; Sengun, Ihsan; Meherremova, Arzu; Ozcelik, Pinar; Balkan, Bengu; Tuga, Celal; Ugur, Muzeyyen; Erdem-Ozdamar, Sevim; Ebru Bekircan-Kurt, Can; Pinar Acar, Nazire; Yilmaz, Ezgi; Caliskan, Yagmur; Orsel, Gulsah; Efendi, Husnu; Aydinlik, Seda; Cavus, Hakan; Kutlu, Ayse; Becerikli, Gulsah; Semiz, Cansu; Tun, Ozlem; Terzi, Murat; Dogan, Baki; Kazim Onar, Musa; Sen, Sedat; Kirbas Cavdar, Tugce; Veske, Adife; Norwood, Fiona; Dimitriou, Aikaterini; Gollogly, Jakit; Mahdi-Rogers, Mohamed; Seddigh, Arshira; Sokratous, Giannis; Maier, Gal; Sohail, Faisal; Jacob, Saiju; Sadalage, Girija; Torane, Pravin; Torane, Pravin; Brown, Claire; Shah, Amna; Sathasivam, Sivakumar; Arndt, Heike; Davies, Debbie; Watling, Dave; Amato, Anthony; Cochrane, Thomas; Salajegheh, Mohammed; Roe, Kristen; Amato, Katherine; Toska, Shirli; Silvestri, Nicholas; Patrick, Kara; Zakalik, Karen; Katz, Jonathan; Miller, Robert; Engel, Marguerite; Forshew, Dallas; Bravver, Elena; Brooks, Benjamin; Sanjak, Mohammed; Plevka, Sarah; Burdette, Maryanne; Cunningham, Scott; Kramer, Megan; Nemeth, Joanne; Schommer, Clara; Scott, Tierney; Juel, Vern; Guptill, Jeffrey; Hobson-Webb, Lisa; Massey, Janice; Beck, Kate; Carnes, Donna; Loor, John; Anderson, Amanda; Pascuzzi, Robert; Bodkin, Cynthia; Kincaid, John; Snook, Riley; Guingrich, Sandra; Micheels, Angela; Chaudhry, Vinay; Corse, Andrea; Mosmiller, Betsy; Kelley, Andrea; Ho, Doreen; Srinivasan, Jayashri; Vytopil, Michal; Jara, Jordan; Ventura, Nicholas; Carter, Cynthia; Donahue, Craig; Herbert, Carol; Scala, Stephanie; Weiner, Elaine; Alam, Sharmeen; Mckinnon, Jonathan; Haar, Laura; Mckinnon, Naya; Alcon, Karan; Mckenna, Kaitlyn; Sattar, Nadia; Daniels, Kevin; Jeffery, Dennis; Freimer, Miriam; Chad Hoyle, Joseph; Kissel, John; Agriesti, Julie; Chelnick, Sharon; Mezache, Louisa; Pineda, Colleen; Muharrem, Filiz; Karam, Chafic; Khoury, Julie; Marburger, Tessa; Kaur, Harpreet; Dimitrova, Diana; Gilchrist, James; Agrawal, Brajesh; Elsayed, Mona; Kohlrus, Stephanie; Ardoin, Angela; Darnell, Taylor; Golden, Laura; Lokaitis, Barbara; Seelbach, Jenna; Goyal, Neelam; Sakamuri, Sarada; T So, Yuen; Paulose, Shirley; Pol, Sabrina; Welsh, Lesly; Bhavaraju-Sanka, Ratna; Tobon Gonzalez, Alejandro; Dishman, Lorraine; Jones, Floyd; Gonzalez, Anna; Padilla, Patricia; Saklad, Amy; Silva, Marcela; Nations, Sharon; Trivedi, Jaya; Hopkins, Steve; Kazamel, Mohamed; Alsharabati, Mohammad; Lu, Liang; Nozaki, Kenkichi; Mumfrey-Thomas, Sandi; Woodall, Amy; Mozaffar, Tahseen; Cash, Tiyonnoh; Goyal, Namita; Roy, Gulmohor; Mathew, Veena; Maqsood, Fatima; Minton, Brian; James Jones, H; Rosenfeld, Jeffrey; Garcia, Rebekah; Echevarria, Laura; Garcia, Sonia; Pulley, Michael; Aranke, Shachie; Ross Berger, Alan; Shah, Jaimin; Shabbir, Yasmeen; Smith, Lisa; Varghese, Mary; Shabbir, Yasmeen; Gutmann, Laurie; Gutmann, Ludwig; Jerath, Nivedita; Nance, Christopher; Swenson, Andrea; Olalde, Heena; Kressin, Nicole; Sieren, Jeri; Barohn, Richard; Dimachkie, Mazen; Glenn, Melanie; Mcvey, April; Pasnoor, Mamatha; Statland, Jeffery; Wang, Yunxia; Liu, Tina; Emmons, Kelley; Jenci, Nicole; Locheke, Jerry; Fondaw, Alex; Johns, Kathryn; Rico, Gabrielle; Walsh, Maureen; Herbelin, Laura; Hafer-Macko, Charlene; Kwan, Justin; Zilliox, Lindsay; Callison, Karen; Young, Valerie; Disanzo, Beth; Naunton, Kerry; Benatar, Michael; Bilsker, Martin; Sharma, Khema; Cooley, Anne; Reyes, Eliana; Michon, Sara-Claude; Sheldon, Danielle; Steele, Julie; Karam, Chafic; Traub, Rebecca; Chopra, Manisha; Vu, Tuan; Katzin, Lara; Mcclain, Terry; Harvey, Brittany; Hart, Adam; Huynh, Kristin; Beydoun, Said; Chilingaryan, Amaiak; Doan, Victor; Droker, Brian; Gong, Hui; Karimi, Sanaz; Lin, Frank; Mcclain, Terry; Polaka, Krishna; Shah, Akshay; Tran, Anh; Akhter, Salma; Malekniazi, Ali; Tandan, Rup; Hehir, Michael; Waheed, Waqar; Lucy, Shannon; Weiss, Michael; Distad, Jane; Strom, Susan; Downing, Sharon; Kim, Bryan; Bertorini, Tulio; Arnold, Thomas; Henderson, Kendrick; Pillai, Rekha; Liu, Ye; Wheeler, Lauren; Hewlett, Jasmine; Vanderhook, Mollie; Nowak, Richard; Dicapua, Daniel; Keung, Benison; Kumar, Aditya; Patwa, Huned; Robeson, Kimberly; Yang, Irene; Nye, Joan; Vu., Hong. - In: NEUROLOGY. - ISSN 1526-632X. - 96:4(2021). [10.1212/WNL.0000000000011207]
Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension
Mantegazza, Renato; Wolfe, Gil I; Muppidi, Srikanth; Wiendl, Heinz; Fujita, Kenji P; O'Brien, Fanny L; Booth, Heather D E; Howard; James F; Claudio Gabriel Mazia; Miguel Wilken; Fabio Barroso; Juliet Saba; Marcelo 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 Melo; Renata Martins Ribeiro; Rosana Rocha; Bruno Bezerra Rosa; Thabata Veiga; Luiz Augusto da Silva; Murilo Santos Engel; Jordana Gonçalves Geraldo; Maria da Penha Ananias Morita; Erica Nogueira Coelho; Gabriel Paiva; Marina Pozo; Natalia 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 Pinto; Aline de Cassia Santos; Acary Souza Bulle Oliveira; Ana Carolina Amaral de Andrade; Marcelo Annes; Liene Duarte Silva; Valeria Cavalcante Lino; Wladimir Pinto; Natália Assis; Fernanda Carrara; Carolina Miranda; Iandra Souza; Patrícia Fernandes; Zaeem Siddiqi; Cecile Phan; Jeffrey Narayan; Derrick Blackmore; Ashley Mallon; Rikki Roderus; Elizabeth Watt; Stanislav Vohanka; Josef Bednarik; Magda Chmelikova; Marek Cierny; Stanislava Toncrova; Jana Junkerova; Barbora Kurkova; Katarina Reguliova; Olga Zapletalova; Jiri Pitha; Iveta Novakova; Michaela Tyblova; Ivana Jurajdova; Marcela Wolfova; Henning Andersen; Thomas Harbo; Lotte Vinge; Susanne Krogh; Anita Mogensen; John Vissing; Joan Højgaard; Nanna Witting; Anne Mette Ostergaard Autzen; Jane Pedersen; Juha-Pekka Erälinna; Mikko Laaksonen; Olli Oksaranta; Tuula Harrison; Jaana Eriksson; Csilla Rozsa; Melinda Horvath; Gabor Lovas; Judit Matolcsi; Gedeonne Jakab; Gyorgyi Szabo; Gedeonne Jakab; Brigitta Szabadosne; Laszlo Vecsei; Livia Dezsi; Edina 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 D'Amato; Raffaele Iorio; Maurizio Inghilleri; Laura Fionda; Vittorio Frasca; Elena Giacomelli; Maria Gori; Diego Lopergolo; Emanuela Onesti; Vittorio Frasca; Maria Gabriele; Francesco Sacca ;Alessandro Filla ;Teresa Costabile; Enrico Marano; Angiola Fasanaro; Angela Marsili ;Giorgia Puorro ;Carlo Antozzi; Silvia Bonanno; Giorgia Camera; Alberta Locatelli; Lorenzo Maggi; Maria Pasanisi; Angela Campanella; Akiyuki Uzawa; Tetsuya Kanai; Naoki Kawaguchi; Masahiro Mori; Yoko 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 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 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; Shuichiro Suzuki; Daisuke Yamamoto; Yoko Ishiyama; Naoko Ishiyama; Mayuko Noshiro; Rumi Takeyama; Kaori Uwasa; Ikuko Yasuda; Anneke 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; So-Hyun Ahn; Dae Lim Koo; Jae-Sung Lim; Chae Won 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 Antonia Alberti Aguilo; Christian Homedes-Pedret; Natalia Julia Palacios; Laura Diez Porras; Valentina Velez Santamaria; Ana Lazaro; Josep Gamez Carbonell; Pilar Sune; Maria Salvado Figueras; Gisela Gili; Gonzalo Mazuela; Isabel Illa; Elena Cortes Vicente; Jordi Diaz-Manera; Luis Antonio Querol Gutiérrez; Ricardo Rojas Garcia; Nuria Vidal; Elisabet Arribas-Ibar; Exuperio Diez Tejedor; Pilar Gomez Salcedo; Mireya Fernandez-Fournier; Pedro Lopez Ruiz; Francisco Javier Rodriguez de Rivera; Mireya Fernandez-Fournier; Maria Sastre; Fredrik Piehl; Albert Hietala; Lena Bjarbo; Ihsan Sengun; Arzu Meherremova; Pinar Ozcelik; Bengu Balkan; Celal Tuga; Muzeyyen Ugur; Sevim Erdem-Ozdamar; Can Ebru Bekircan-Kurt; Nazire Pinar Acar; Ezgi Yilmaz; Yagmur Caliskan; Gulsah Orsel; Husnu Efendi; Seda Aydinlik; Hakan Cavus; Ayse Kutlu; Gulsah Becerikli; Cansu Semiz; Ozlem Tun; Murat Terzi; Baki Dogan; Musa Kazim Onar; Sedat Sen; 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 Shah; Sivakumar Sathasivam; Heike Arndt; Debbie Davies; Dave Watling; Anthony Amato; Thomas Cochrane; Mohammed Salajegheh; Kristen Roe; Katherine Amato; Shirli Toska; Nicholas Silvestri; Kara Patrick; Karen Zakalik; Jonathan Katz; Robert Miller; Marguerite Engel; Dallas Forshew; Elena Bravver; Benjamin Brooks; Mohammed Sanjak; Sarah Plevka; Maryanne Burdette; Scott Cunningham; Megan Kramer; Joanne Nemeth; Clara Schommer; Tierney Scott; Vern Juel; Jeffrey Guptill; Lisa Hobson-Webb; Janice Massey; Kate Beck; Donna Carnes; John Loor; Amanda Anderson; Robert Pascuzzi; Cynthia Bodkin; John Kincaid; Riley Snook; Sandra Guingrich; Angela Micheels; Vinay Chaudhry; Andrea Corse; Betsy Mosmiller; Andrea Kelley; Doreen 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 Freimer; Joseph Chad Hoyle; John Kissel; Julie Agriesti; Sharon Chelnick; Louisa Mezache; Colleen Pineda; Filiz Muharrem; Chafic Karam; Julie Khoury; Tessa Marburger; Harpreet Kaur; Diana Dimitrova; James Gilchrist; Brajesh Agrawal; Mona Elsayed; Stephanie Kohlrus; Angela Ardoin; Taylor Darnell; Laura Golden; Barbara Lokaitis; Jenna Seelbach; Neelam Goyal; Sarada Sakamuri; Yuen T So; Shirley Paulose; Sabrina Pol; Lesly Welsh; Ratna Bhavaraju-Sanka; Alejandro Tobon Gonzalez; Lorraine Dishman; Floyd Jones; Anna Gonzalez; Patricia Padilla; Amy Saklad; Marcela Silva; Sharon Nations; Jaya Trivedi; Steve Hopkins; Mohamed Kazamel; Mohammad Alsharabati; Liang Lu; Kenkichi Nozaki; Sandi Mumfrey-Thomas; Amy Woodall; Tahseen Mozaffar; Tiyonnoh Cash; Namita Goyal; Gulmohor Roy; Veena Mathew; Fatima Maqsood; Brian Minton; H James Jones; Jeffrey Rosenfeld; Rebekah Garcia; Laura Echevarria; Sonia Garcia; Michael Pulley; Shachie Aranke; Alan Ross Berger; Jaimin Shah; Yasmeen Shabbir; Lisa Smith; Mary Varghese; Yasmeen Shabbir; Laurie Gutmann; Ludwig Gutmann; Nivedita Jerath; Christopher Nance; Andrea Swenson; Heena Olalde; Nicole Kressin; Jeri Sieren; Richard Barohn; Mazen Dimachkie; Melanie Glenn; April McVey; Mamatha Pasnoor; Jeffery Statland; Yunxia Wang; Tina Liu; Kelley Emmons; Nicole Jenci; Jerry Locheke; Alex Fondaw; Kathryn Johns; Gabrielle Rico; Maureen Walsh; Laura Herbelin; Charlene Hafer-Macko; Justin Kwan; Lindsay Zilliox; Karen Callison; Valerie Young; Beth DiSanzo; Kerry Naunton; Michael Benatar; Martin Bilsker; Khema Sharma; Anne Cooley; Eliana Reyes; Sara-Claude Michon; Danielle Sheldon; Julie Steele; Chafic Karam; Rebecca Traub; Manisha Chopra; Tuan Vu; Lara Katzin; Terry McClain; Brittany Harvey; Adam Hart; Kristin Huynh; Said Beydoun; Amaiak Chilingaryan; Victor Doan; Brian Droker; Hui Gong; Sanaz Karimi; Frank Lin; Terry McClain; Krishna Polaka; Akshay Shah; Anh Tran; Salma Akhter; Ali Malekniazi; Rup Tandan; Michael Hehir; Waqar Waheed; Shannon Lucy; Michael Weiss; Jane Distad; Susan Strom; Sharon Downing; Bryan Kim; Tulio Bertorini; Thomas Arnold; Kendrick Henderson; Rekha Pillai; Ye Liu; Lauren Wheeler; Jasmine Hewlett; Mollie Vanderhook; Richard Nowak; Daniel Dicapua; Benison Keung; Aditya Kumar; Huned Patwa; Kimberly Robeson; Irene Yang; Joan Nye; Hong Vu.
2021
Abstract
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 support the use of eculizumab in this previously difficult-to-treat patient population. Clinicaltrialsgov identifier: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. Classification of evidence: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.
Citazione
Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension / Renato, Mantegazza; Gil I, Wolfe; Srikanth, Muppidi; Heinz, Wiendl; Kenji P, Fujita; Fanny L, O'Brien; Heather D E, Booth; Howard, ; F, James; Gabriel Mazia, Claudio; Wilken, Miguel; Barroso, Fabio; Saba, Juliet; Rugiero, Marcelo; Bettini, Mariela; Chaves, Marcelo; Vidal, Gonzalo; Dalila Garcia, Alejandra; De Bleecker, Jan; Van den Abeele, Guy; de Koning, Kathy; De Mey, Katrien; Mercelis, Rudy; Mahieu, Délphine; Wagemaekers, Linda; Van Damme, Philip; Depreitere, Annelies; Schotte, Caroline; Smetcoren, Charlotte; Stevens, Olivier; Van Daele, Sien; Vandenbussche, Nicolas; Vanhee, Annelies; Verjans, Sarah; Vynckier, Jan; D'Hont, Ann; Tilkin, Petra; Alves de Siqueira Carvalho, Alzira; Dias Brockhausen, Igor; Feder, David; Ambrosio, Daniel; Lovasamela César, Gabor; Paula Melo, Ana; Martins Ribeiro, Renata; Rocha, Rosana; Bezerra Rosa, Bruno; Veiga, Thabata; Augusto da Silva, Luiz; Santos Engel, Murilo; Gonçalves Geraldo, Jordana; da Penha Ananias Morita, Maria; Nogueira Coelho, Erica; Paiva, Gabriel; Pozo, Marina; Prando, Natalia; Dada Martineli Torres, Debora; Fernanda Butinhao, Cristiani; Duran, Gustavo; Augusto Suriane Fialho, Tomás; Cristina Gomes da Silva, Tamires; Otavio Maia Gonçalves, Luiz; Eduardo Pazetto, Lucas; Renata Cubas Volpe, Luciana; Souza Duca, Luciana; AndréGheller Friedrich, Maurício; Guerreiro, Alexandre; Guerreiro, Alexandre; Mohr, Henrique; Pereira Martins, Maurer; da Cruz Pacheco, Daiane; Ferreira, Luciana; Paula Macagnan, Ana; Pinto, Graziela; de Cassia Santos, Aline; Souza Bulle Oliveira, Acary; Carolina Amaral de Andrade, Ana; Annes, Marcelo; Duarte Silva, Liene; Cavalcante Lino, Valeria; Pinto, Wladimir; Assis, Natália; Carrara, Fernanda; Miranda, Carolina; Souza, Iandra; Fernandes, Patrícia; Siddiqi, Zaeem; Phan, Cecile; Narayan, Jeffrey; Blackmore, Derrick; Mallon, Ashley; Roderus, Rikki; Watt, Elizabeth; Vohanka, Stanislav; Bednarik, Josef; Chmelikova, Magda; Cierny, Marek; Toncrova, Stanislava; Junkerova, Jana; Kurkova, Barbora; Reguliova, Katarina; Zapletalova, Olga; Pitha, Jiri; Novakova, Iveta; Tyblova, Michaela; Jurajdova, Ivana; Wolfova, Marcela; Andersen, Henning; Harbo, Thomas; Vinge, Lotte; Krogh, Susanne; Mogensen, Anita; Vissing, John; Højgaard, Joan; Witting, Nanna; Mette Ostergaard Autzen, Anne; Pedersen, Jane; Erälinna, Juha-Pekka; Laaksonen, Mikko; Oksaranta, Olli; Harrison, Tuula; Eriksson, Jaana; Rozsa, Csilla; Horvath, Melinda; Lovas, Gabor; Matolcsi, Judit; Jakab, Gedeonne; Szabo, Gyorgyi; Jakab, Gedeonne; Szabadosne, Brigitta; Vecsei, Laszlo; Dezsi, Livia; Varga, Edina; Konyane, Monika; Antonini, Giovanni; Di Pasquale, Antonella; Garibaldi, Matteo; Morino, Stefania; Troili, Fernanda; Fionda, Laura; Di Pasquale, Antonella; Evoli, Amelia; Emilio Alboini, Paolo; D'Amato, Valentina; Iorio, Raffaele; Inghilleri, Maurizio; Fionda, Laura; Frasca, Vittorio; Giacomelli, Elena; Gori, Maria; Lopergolo, Diego; Onesti, Emanuela; Frasca, Vittorio; Gabriele, Maria; Sacca, Francesco; Filla, Alessandro; Costabile, Teresa; Marano, Enrico; Fasanaro, Angiola; Marsili, Angela; Puorro, Giorgia; Antozzi, Carlo; Bonanno, Silvia; Camera, Giorgia; Locatelli, Alberta; Maggi, Lorenzo; Pasanisi, Maria; Campanella, Angela; Uzawa, Akiyuki; Kanai, Tetsuya; Kawaguchi, Naoki; Mori, Masahiro; Kaneko, Yoko; Kanzaki, Akiko; Kobayashi, Eri; Murai, Hiroyuki; Masaki, Katsuhisa; Matsuse, Dai; Matsushita, Takuya; Uehara, Taira; Shimpo, Misa; Jingu, Maki; Kikutake, Keiko; Nakamura, Yumiko; Sano, Yoshiko; Utsugisawa, Kimiaki; Nagane, Yuriko; Kamegamori, Ikuko; Tsuda, Tomoko; Fujii, Yuko; Futono, Kazumi; Ozawa, Yukiko; Mizugami, Aya; Saito, Yuka; Samukawa, Makoto; Suzuki, Hidekazu; Morikawa, Miyuki; Kamakura, Sachiko; Miyawaki, Eriko; Okumura, Meinoshin; Funaka, Soichiro; Kawamura, Tomohiro; Nakamori, Masayuki; Takahashi, Masanori; Taichi, Namie; Hasuike, Tomoya; Higuchi, Eriko; Kobayashi, Hisako; Osakada, Kaori; Shiraishi, Hirokazu; Miyazaki, Teiichiro; Motomura, Masakatsu; Mukaino, Akihiro; Yoshimura, Shunsuke; Asada, Shizuka; Yoshida, Seiko; Amamoto, Shoko; Kobashikawa, Tomomi; Koga, Megumi; Yasuko, Maeda; Takada, Kazumi; Takada, Mihoko; Tsurumaru, Masako; Yamashita, Yumi; Suzuki, Yasushi; Akiyama, Tetsuya; Narikawa, Koichi; Tano, Ohito; Tsukita, Kenichi; Kurihara, Rikako; Meguro, Fumie; Fukuda, Yusuke; Sato, Miwako; Imai, Tomihiro; Tsuda, Emiko; Shimohama, Shun; Hayashi, Takashi; Hisahara, Shin; Imai, Tomihiro; Kawamata, Jun; Murahara, Takashi; Saitoh, Masaki; Shimohama, Shun; Suzuki, Shuichiro; Yamamoto, Daisuke; Ishiyama, Yoko; Ishiyama, Naoko; Noshiro, Mayuko; Takeyama, Rumi; Uwasa, Kaori; Yasuda, Ikuko; van der Kooi, Anneke; de Visser, Marianne; Gibson, Tamar; Kim, Byung-Jo; Nyoung Lee, Chang; Seo Koo, Yong; Youl Seok, Hung; Nam Kang, Hoo; Ra, Hyejin; Joon Kim, Byoung; Bin Cho, Eun; Choi, Misong; Lee, Hyelim; Min, Ju-Hong; Seok, Jinmyoung; Lee, Jieun; Yoon Koh, Da; Kwon, Juyoung; Park, Sangae; Haw Choi, Eun; Hong, Yoon-Ho; Ahn, So-Hyun; Lim Koo, Dae; Lim, Jae-Sung; Won Shin, Chae; Ye Hwang, Ji; Kim, Miri; Min Kim, Seung; Jeong, Ha-Neul; Jung, Jinwoo; Kim, Yool-Hee; Seok Lee, Hyung; Young Shin, Ha; Bi Hwang, Eun; Shin, Miju; Casasnovas, Carlos; Antonia Alberti Aguilo, Maria; Homedes-Pedret, Christian; Julia Palacios, Natalia; Diez Porras, Laura; Velez Santamaria, Valentina; Lazaro, Ana; Gamez Carbonell, Josep; Sune, Pilar; Salvado Figueras, Maria; Gili, Gisela; Mazuela, Gonzalo; Illa, Isabel; Cortes Vicente, Elena; Diaz-Manera, Jordi; Antonio Querol Gutiérrez, Luis; Rojas Garcia, Ricardo; Vidal, Nuria; Arribas-Ibar, Elisabet; Diez Tejedor, Exuperio; Gomez Salcedo, Pilar; Fernandez-Fournier, Mireya; Lopez Ruiz, Pedro; Javier Rodriguez de Rivera, Francisco; Fernandez-Fournier, Mireya; Sastre, Maria; Piehl, Fredrik; Hietala, Albert; Bjarbo, Lena; Sengun, Ihsan; Meherremova, Arzu; Ozcelik, Pinar; Balkan, Bengu; Tuga, Celal; Ugur, Muzeyyen; Erdem-Ozdamar, Sevim; Ebru Bekircan-Kurt, Can; Pinar Acar, Nazire; Yilmaz, Ezgi; Caliskan, Yagmur; Orsel, Gulsah; Efendi, Husnu; Aydinlik, Seda; Cavus, Hakan; Kutlu, Ayse; Becerikli, Gulsah; Semiz, Cansu; Tun, Ozlem; Terzi, Murat; Dogan, Baki; Kazim Onar, Musa; Sen, Sedat; Kirbas Cavdar, Tugce; Veske, Adife; Norwood, Fiona; Dimitriou, Aikaterini; Gollogly, Jakit; Mahdi-Rogers, Mohamed; Seddigh, Arshira; Sokratous, Giannis; Maier, Gal; Sohail, Faisal; Jacob, Saiju; Sadalage, Girija; Torane, Pravin; Torane, Pravin; Brown, Claire; Shah, Amna; Sathasivam, Sivakumar; Arndt, Heike; Davies, Debbie; Watling, Dave; Amato, Anthony; Cochrane, Thomas; Salajegheh, Mohammed; Roe, Kristen; Amato, Katherine; Toska, Shirli; Silvestri, Nicholas; Patrick, Kara; Zakalik, Karen; Katz, Jonathan; Miller, Robert; Engel, Marguerite; Forshew, Dallas; Bravver, Elena; Brooks, Benjamin; Sanjak, Mohammed; Plevka, Sarah; Burdette, Maryanne; Cunningham, Scott; Kramer, Megan; Nemeth, Joanne; Schommer, Clara; Scott, Tierney; Juel, Vern; Guptill, Jeffrey; Hobson-Webb, Lisa; Massey, Janice; Beck, Kate; Carnes, Donna; Loor, John; Anderson, Amanda; Pascuzzi, Robert; Bodkin, Cynthia; Kincaid, John; Snook, Riley; Guingrich, Sandra; Micheels, Angela; Chaudhry, Vinay; Corse, Andrea; Mosmiller, Betsy; Kelley, Andrea; Ho, Doreen; Srinivasan, Jayashri; Vytopil, Michal; Jara, Jordan; Ventura, Nicholas; Carter, Cynthia; Donahue, Craig; Herbert, Carol; Scala, Stephanie; Weiner, Elaine; Alam, Sharmeen; Mckinnon, Jonathan; Haar, Laura; Mckinnon, Naya; Alcon, Karan; Mckenna, Kaitlyn; Sattar, Nadia; Daniels, Kevin; Jeffery, Dennis; Freimer, Miriam; Chad Hoyle, Joseph; Kissel, John; Agriesti, Julie; Chelnick, Sharon; Mezache, Louisa; Pineda, Colleen; Muharrem, Filiz; Karam, Chafic; Khoury, Julie; Marburger, Tessa; Kaur, Harpreet; Dimitrova, Diana; Gilchrist, James; Agrawal, Brajesh; Elsayed, Mona; Kohlrus, Stephanie; Ardoin, Angela; Darnell, Taylor; Golden, Laura; Lokaitis, Barbara; Seelbach, Jenna; Goyal, Neelam; Sakamuri, Sarada; T So, Yuen; Paulose, Shirley; Pol, Sabrina; Welsh, Lesly; Bhavaraju-Sanka, Ratna; Tobon Gonzalez, Alejandro; Dishman, Lorraine; Jones, Floyd; Gonzalez, Anna; Padilla, Patricia; Saklad, Amy; Silva, Marcela; Nations, Sharon; Trivedi, Jaya; Hopkins, Steve; Kazamel, Mohamed; Alsharabati, Mohammad; Lu, Liang; Nozaki, Kenkichi; Mumfrey-Thomas, Sandi; Woodall, Amy; Mozaffar, Tahseen; Cash, Tiyonnoh; Goyal, Namita; Roy, Gulmohor; Mathew, Veena; Maqsood, Fatima; Minton, Brian; James Jones, H; Rosenfeld, Jeffrey; Garcia, Rebekah; Echevarria, Laura; Garcia, Sonia; Pulley, Michael; Aranke, Shachie; Ross Berger, Alan; Shah, Jaimin; Shabbir, Yasmeen; Smith, Lisa; Varghese, Mary; Shabbir, Yasmeen; Gutmann, Laurie; Gutmann, Ludwig; Jerath, Nivedita; Nance, Christopher; Swenson, Andrea; Olalde, Heena; Kressin, Nicole; Sieren, Jeri; Barohn, Richard; Dimachkie, Mazen; Glenn, Melanie; Mcvey, April; Pasnoor, Mamatha; Statland, Jeffery; Wang, Yunxia; Liu, Tina; Emmons, Kelley; Jenci, Nicole; Locheke, Jerry; Fondaw, Alex; Johns, Kathryn; Rico, Gabrielle; Walsh, Maureen; Herbelin, Laura; Hafer-Macko, Charlene; Kwan, Justin; Zilliox, Lindsay; Callison, Karen; Young, Valerie; Disanzo, Beth; Naunton, Kerry; Benatar, Michael; Bilsker, Martin; Sharma, Khema; Cooley, Anne; Reyes, Eliana; Michon, Sara-Claude; Sheldon, Danielle; Steele, Julie; Karam, Chafic; Traub, Rebecca; Chopra, Manisha; Vu, Tuan; Katzin, Lara; Mcclain, Terry; Harvey, Brittany; Hart, Adam; Huynh, Kristin; Beydoun, Said; Chilingaryan, Amaiak; Doan, Victor; Droker, Brian; Gong, Hui; Karimi, Sanaz; Lin, Frank; Mcclain, Terry; Polaka, Krishna; Shah, Akshay; Tran, Anh; Akhter, Salma; Malekniazi, Ali; Tandan, Rup; Hehir, Michael; Waheed, Waqar; Lucy, Shannon; Weiss, Michael; Distad, Jane; Strom, Susan; Downing, Sharon; Kim, Bryan; Bertorini, Tulio; Arnold, Thomas; Henderson, Kendrick; Pillai, Rekha; Liu, Ye; Wheeler, Lauren; Hewlett, Jasmine; Vanderhook, Mollie; Nowak, Richard; Dicapua, Daniel; Keung, Benison; Kumar, Aditya; Patwa, Huned; Robeson, Kimberly; Yang, Irene; Nye, Joan; Vu., Hong. - In: NEUROLOGY. - ISSN 1526-632X. - 96:4(2021). [10.1212/WNL.0000000000011207]
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande. La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.