Eculizumab improves fatigue in refractory generalized myasthenia gravis
Authors: Andersen Henning , Mantegazza Renato , Wang Jing Jing , O’Brien Fanny , Patra Kaushik , Howard James F. ,   The REGAIN Study Group, Mazia Claudio Gabriel , Wilken Miguel , Barroso Fabio , Saba Juliet , Rugiero Marcelo , Bettini Mariela , Chaves Marcelo , Vidal Gonzalo , Garcia Alejandra Dalila , 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’Hondt Ann , Tilkin Petra , Alves de Siqueira Carvalho Alzira , Dias Brockhausen Igor , Feder David , Ambrosio Daniel , César Pamela , Melo Ana Paula , Martins Ribeiro Renata , Rocha Rosana , Bezerra Rosa Bruno , Veiga Thabata , da Silva Luiz Augusto , Santos Engel Murilo , Gonçalves Geraldo Jordana , da Penha Ananias Morita Maria , Nogueira Coelho Erica , Paiva Gabriel , Pozo Marina , Prando Natalia , Martineli Torres Debora Dada , Butinhao Cristiani Fernanda , Duran Gustavo , Gomes da Silva Tamires Cristina , Otavio Maia Gonçalves Luiz , Pazetto Lucas Eduardo , Fialho Tomás Augusto Suriane , Renata Cubas Volpe Luciana , Souza Duca Luciana , Gheller Friedrich Maurício André , Guerreiro Alexandre , Mohr Henrique , Pereira Martins Maurer , da Cruz Pacheco Daiane , Ferreira Luciana , Macagnan Ana Paula , Pinto Graziela , de Cassia Santos Aline , Souza Bulle Oliveira Acary , Amaral Andrade Ana Carolina , Annes Marcelo , Duarte Silva Liene , Cavalcante Lino Valeria , Pinto Wladimir , Assis Natália , Carrara Fernanda , Miranda Carolina , Souza Iandra , Fernandes Patricia , 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 , Harbo Thomas , Vinge Lotte , Krogh Susanne , Mogensen Anita , Vissing John , Højgaard Joan , Witting Nanna , Ostergaard Autzen Anne , Pedersen Jane , Eralinna Juha-Pekka , Laaksonen Mikko , Oksaranta Olli , Harrison Tuula , Eriksson Jaana , Rozsa Csilla , Horvath Melinda , Lovas Gabor , Matolcsi Judit , 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 , Filla Allessandro , Costabile Teresa , Marano Enrico , Saccà Francesco , Fasanaro Angiola , Marsili Angela , Puorro Giorgia , Antozzi Carlo , Bonanno Silvia , Camera Giorgia , Locatelli Alberta , Maggi Lorenzo , Pasanisi Maria , Campanella Angela , Evoli Amelia , Alboini Paolo Emilio , D’Amato Valentina , Iorio Raffaele , Inghilleri Maurizio , Fionda Laura , Frasca Vittorio , Giacomelli Elena , Gori Maria , Lopergolo Diego , Onesti Emanuela , Frasca Vittorio , Gabriele Maria , 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 , Suzuki Hidekazu , Morikawa Miyuki , Samukawa Makoto , Kamakura Sachiko , Miyawaki Eriko , Shiraishi Hirokazu , Mitazaki Teiichiro , Motomura Masakatsu , Mukaino Akihiro , Yoshimura Shunsuke , Asada Shizuka , Yoshida Seiko , Amamoto Shoko , Kobashikawa Tomomi , Koga Megumi , Maeda Yasuko , 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 , Okumura Meinoshin , Funaka Soichiro , Kawamura Tomohiro , Makamori Masayuki , Takahashi Masanori , Taichi Namie , Hasuike Tomoya , Higuchi Eriko , Kobayashi Hisako , Osakada Kaori , Imai Tomihiro , Tsuda Emiko , Shimohama Shun , Hayashi Takashi , Hisahara Shin , Kawamata Jun , Murahara Takashi , Saitoh Masaki , 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 , Lee Chang Nyoung , Koo Yong Seo , Seok Hung Youl , Kang Hoo Nam , Ra HyeJin , Kim Byoung Joon , Cho Eun Bin , Choi MiSong , Lee HyeLim , Min Ju-Hong , Seok Jinmyoung , Lee JiEun , Koh Da Yoon , Kwon JuYoung , Park SangAe , Choi Eun Hwa , Hong Yoon-Ho , Ahn So-Hyun , Koo Dae Lim , Lim Jae-Sung , Shin ChaeWon , Hwang Ji Ye , Kim Miri , Kim Seung Min , Jeong Ha-Neul , Jung JinWoo , Kim Yool-hee , Lee Hyung Seok , Shin Ha Young , Hwang Eun Bi , Shin Miju , Casasnovas Carlos , Alberti Aguilo Maria Antonia , Homedes-Pedret Christian , Julia Palacios Natalia , Diez Porras Laura , Velez Santamaria Valentina , Lazaro Ana , Diez Tejedor Exuperio , Gomez Salcedo Pilar , Fernandez-Fournier Mireya , Lopez Ruiz Pedro , Rodriguez de Rivera Francisco Javier , Sastre Maria , Gamez Josep , Sune Pilar , Salvado Maria , Gili Gisela , Mazuela Gonzalo , Illa Isabel , Cortes Vicente Elena , Diaz-Manera Jordi , Querol Gutierrez Luis Antonio , Rojas Garcia Ricardo , Vidal Nuria , Arribas-Ibar Elisabet , Piehl Fredrik , Hietala Albert , Bjarbo Lena , Sengun Ihsan , Meherremova Arzu , Ozcelik Pinar , Balkan Bengu , Tuga Celal , Ugur Muzeyyen , Erdem-Ozdamar Sevim , Bekircan-Kurt Can Ebru , Acar Nazire Pinar , Yilmaz Ezgi , Caliskan Yagmur , Orsel Gulsah , Efendi Husnu , Aydinlik Seda , Cavus Hakan , Kutlu Ayse , Becerikli Gulsar , Semiz Cansu , Tun Ozlem , Terzi Murat , Dogan Baki , Onar Musa Kazim , 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 , Brown Claire , Shah Amna , Sathasivam Sivakumar , Arndt Heike , Davies Debbie , Watling Dave , Amato Anthony , Cochrane Thomas , Salajegheh Mohammed , Roe Kristen , Amato Katherine , Toska Shirli , Wolfe Gil , Silvestri Nicholas , Patrick Kara , Zakalik Karen , Katz Jonathan , Miller Robert , Engel Marguerite , Forshew Dallas , Bravver Elena , Brooks Benjamin , Plevka Sarah , Burdette Maryanne , Cunningham Scott , Sanjak Mohammad , Kramer Megan , Nemeth Joanne , Schommer Clara , Tierney Scott , 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 , Scala Stephanie , Carter Cynthia , Donahue Craig , Herbert Carol , Weiner Elaine , Alam Sharmeen , McKinnon Jonathan , Haar Laura , McKinnon Naya , Alcon Karan , McKenna Kaitlyn , Sattar Nadia , Daniels Kevin , Jeffery Dennis , Kissel John , Freimer Miriam , Hoyle Joseph Chad , 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 , Andoin Angela , Darnell Taylor , Golden Laura , Lokaitis Barbara , Seelback Jenna , Muppidi Srikanth , Goyal Neelam , Sakamuri Sarada , So Yuen T. , Paulose Shirley , Pol Sabrina , Welsh Lesly , Bhavaraju-Sanka Ratna , Tobon Gonzales 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 , Jones H. James , Rosenfeld Jeffrey , Garcia Rebekah , Echevarria Laura , Garcia Sonia , Pulley Michael , Aranke Shachie , Berger Alan Ross , Shah Jaimin , Shabbir Yasmeen , Smith Lisa , Varghese Mary , 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 Junxia , 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 , Chopra Manisha , Traub Rebecca , 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 , Pokala 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 , Hendersen 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 
Published: March 2019

Purpose

To evaluate the effect of eculizumab on perceived fatigue in patients with anti-acetylcholine receptor antibody-positive, refractory, generalized myasthenia gravis (MG) using the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue subscale, and to evaluate correlations between improvements in Neuro-QOL Fatigue and other clinical endpoints.

Methods

Neuro-QOL Fatigue, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and the 15-item MG Quality of Life (MG-QOL15) scales were administered during the phase 3, randomized, placebo-controlled REGAIN study (eculizumab, n = 62; placebo, n = 63) and subsequent open-label extension (OLE). Data were analyzed using repeated-measures models. Correlations between changes in Neuro-QOL Fatigue and in MG-ADL, QMG, and MG-QOL15 scores were determined at REGAIN week 26.

Results

At REGAIN week 26, eculizumab-treated patients showed significantly greater improvements in Neuro-QOL Fatigue scores than placebo-treated patients (consistent with improvements in MG-ADL, QMG, and MG-QOL15 scores previously reported in REGAIN). Improvements with eculizumab were sustained through OLE week 52. Correlations between Neuro-QOL Fatigue and MG-QOL15, MG-ADL, and QMG scores were strong for eculizumab-treated patients at REGAIN week 26, and strong, moderate, and weak, respectively, for placebo-treated patients.

Conclusions

Compared with placebo, eculizumab was associated with improvements in perceived fatigue that strongly correlated with improvements in MG-specific outcome measures.

Trial ID Registration: NCT01997229, NCT02301624.