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J Neurol Sci. 2019 Dec 15;407:116419. doi: 10.1016/j.jns.2019.08.004. Epub 2019 Aug 3.

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study.

Collaborators (478)

Mazia CG11, Wilken M11, Barroso F11, Saba J11, Rugiero M12, Bettini M12, Chaves M12, Vidal G12, Garcia AD12, De Bleecker J13, Van den Abeele G13, de Koning K13, De Mey K13, Mercelis R14, Mahieu D14, Wagemaekers L14, Van Damme P15, Depreitere A16, Schotte C16, Smetcoren C16, Stevens O16, Van Daele S16, Vandenbussche N16, Vanhee A16, Verjans S16, Vynckier J16, D'Hondt A16, Tilkin P16, Alves de Siqueira Carvalho A17, Dias Brockhausen I17, Feder D17, Ambrosio D17, César P17, Melo AP17, Martins Ribeiro R17, Rocha R17, Bezerra Rosa B17, Veiga T17, da Silva LA17, Santos Engel M17, Gonçalves Geraldo J17, Ananias Morita MDP18, Nogueira Coelho E18, Paiva G18, Pozo M18, Prando N18, Martineli Torres DD18, Butinhao CF18, Duran G18, Gomes da Silva TC18, Otavio Maia Gonçalves L18, Pazetto LE18, Fialho TAS18, Renata Cubas Volpe L18, Souza Duca L18, Souza Bulle Oliveira A19, Amaral Andrade AC19, Annes M19, Duarte Silva L19, Cavalcante Lino V19, Pinto W19, Assis N19, Carrara F19, Miranda C19, Souza I19, Fernandes P19, Siddiqi Z20, Phan C20, Narayan J20, Blackmore D20, Mallon A20, Roderus R20, Watt E20, Junkerova J21, Kurkova B21, Reguliova K21, Zapletalova O21, Pitha J22, Novakova I22, Tyblova M22, Jurajdova I22, Wolfova M22, Andersen H23, Harbo T23, Vinge L23, Krogh S23, Mogensen A23, Vissing J24, Højgaard J24, Witting N24, Mette Ostergaard Autzen A24, Pedersen J24, Eralinna JP25, Laaksonen M25, Oksaranta O25, Harrison T25, Eriksson J25, Rozsa C26, Horvath M26, Lovas G26, Matolcsi J26, Szabo G26, Jakab G26, Szabadosne B26, Antonini G27, Di Pasquale A27, Garibaldi M27, Morino S27, Troili F27, Fionda L27, Filla A28, Costabile T28, Marano E28, Saccà F28, Fasanaro A28, Marsili A28, Puorro G28, Mantegazza R29, Antozzi C29, Bonanno S29, Camera G29, Locatelli A29, Maggi L29, Pasanisi M29, Campanella A29, Evoli A30, Alboini PE30, D'Amato V30, Iorio R30, Kanai T31, Kawaguchi N31, Mori M31, Kaneko Y31, Kanzaki A31, Kobayashi E31, Masaki K32, Matsuse D32, Matsushita T32, Uehara T32, Shimpo M32, Jingu M32, Kikutake K32, Nakamura Y32, Sano Y32, Nagane Y33, Kamegamori I33, Tsuda T33, Fujii Y33, Futono K33, Ozawa Y33, Mizugami A33, Saito Y33, Morikawa M34, Samukawa M34, Kamakura S34, Miyawaki E34, Mitazaki T35, Motomura M35, Mukaino A35, Yoshimura S35, Asada S35, Yoshida S35, Amamoto S35, Kobashikawa T35, Koga M35, Maeda Y35, Takada K35, Takada M35, Tsurumaru M35, Yamashita Y35, Akiyama T36, Narikawa K36, Tano O36, Tsukita K36, Kurihara R36, Meguro F36, Fukuda Y36, Sato M36, Funaka S37, Kawamura T37, Makamori M37, Takahashi M37, Taichi N37, Hasuike T37, Higuchi E37, Kobayashi H37, Osakada K37, Tsuda E38, Shimohama S38, Hayashi T38, Hisahara S38, Kawamata J38, Murahara T38, Saitoh M38, Suzuki S38, Yamamoto D38, Ishiyama Y38, Ishiyama N38, Noshiro M38, Takeyama R38, Uwasa K38, Yasuda I38, van der Kooi A39, de Visser M39, Gibson T39, Casasnovas C40, Alberti Aguilo MA40, Homedes-Pedret C40, Julia Palacios N40, Diez Porras L40, Velez Santamaria V40, Lazaro A40, Diez Tejedor E41, Gomez Salcedo P41, Fernandez-Fournier M41, Lopez Ruiz P41, Rodriguez de Rivera FJ41, Sastre M41, Gamez J42, Sune P42, Salvado M42, Gili G42, Mazuela G42, Illa I43, Cortes Vicente E43, Diaz-Manera J43, Querol Gutierrez LA43, Rojas Garcia R43, Vidal N43, Arribas-Ibar E43, Piehl F44, Hietala A44, Bjarbo L44, Sengun I45, Meherremova A45, Ozcelik P45, Balkan B45, Tuga C45, Ugur M45, Erdem-Ozdamar S46, Bekircan-Kurt CE46, Acar NP46, Yilmaz E46, Caliskan Y46, Orsel G46, Efendi H47, Aydinlik S47, Cavus H47, Kutlu A47, Becerikli G47, Semiz C47, Tun O47, Terzi M48, Dogan B48, Onar MK48, Sen S48, Kirbas Cavdar T48, Veske A48, Norwood F49, Dimitriou A49, Gollogly J49, Mahdi-Rogers M49, Seddigh A49, Sokratous G49, Maier G49, Sohail F49, Jacob S50, Sadalage G50, Torane P50, Brown C50, Shah A50, Sathasivam S51, Arndt H51, Davies D51, Watling D51, Amato A52, Cochrane T52, Salajegheh M52, Roe K52, Amato K52, Toska S52, Wolfe G53, Silvestri N53, Patrick K53, Zakalik K53, Katz J54, Miller R54, Engel M54, Forshew D54, Bravver E55, Brooks B55, Plevka S55, Burdette M55, Cunningham S55, Sanjak M55, Kramer M55, Nemeth J55, Schommer C55, Tierney S55, Juel V56, Guptill J56, Hobson-Webb L56, Massey J56, Beck K56, Carnes D56, Loor J56, Anderson A56, Pascuzzi R57, Bodkin C57, Kincaid J57, Snook R57, Guingrich S57, Micheels A57, Chaudhry V58, Corse A58, Mosmiller B58, Kelley A58, Ho D59, Srinivasan J59, Vytopil M59, Jara J59, Ventura N59, Scala S59, Carter C59, Donahue C59, Herbert C59, Weiner E59, Alam S59, McKinnon J60, Haar L60, McKinnon N60, Alcon K60, McKenna K60, Sattar N60, Daniels K60, Jeffery D60, Freimer M61, Hoyle JC61, Kissel J61, Agriesti J61, Chelnick S61, Mezache L61, Pineda C61, Muharrem F61, Karam C62, Khoury J62, Marburger T62, Kaur H62, Dimitrova D62, Gilchrist J63, Agrawal B63, Elsayed M63, Kohlrus S63, Andoin A63, Darnell T63, Golden L63, Lokaitis B63, Seelback J63, Muppidi S64, Goyal N64, Sakamuri S64, So YT64, Paulose S64, Pol S64, Welsh L64, Bhavaraju-Sanka R65, Tobon Gonzales A65, Dishman L65, Jones F65, Gonzalez A65, Padilla P65, Saklad A65, Silva M65, Kazamel M66, Alsharabati M66, Lu L66, Nozaki K66, Mumfrey-Thomas S66, Woodall A66, Mozaffar T67, Cash T67, Goyal N67, Roy G67, Mathew V67, Maqsood F67, Minton B67, Jones HJ68, Rosenfeld J68, Garcia R68, Echevarria L68, Garcia S68, Pulley M69, Aranke S69, Berger AR69, Shah J69, Shabbir Y69, Smith L69, Varghese M69, Gutmann L70, Gutmann L70, Jerath N70, Nance C70, Swenson A70, Olalde H70, Kressin N70, Sieren J70, Barohn R71, Dimachkie M71, Glenn M71, McVey A71, Pasnoor M71, Statland J71, Wang Y71, Liu T71, Emmons K71, Jenci N71, Locheke J71, Fondaw A71, Johns K71, Rico G71, Walsh M71, Herbelin L71, Hafer-Macko C72, Kwan J72, Zilliox L72, Callison K72, Young V72, DiSanzo B72, Naunton K72, Benatar M73, Bilsker M73, Sharma K73, Cooley A73, Reyes E73, Michon SC73, Sheldon D73, Steele J73, Howard J Jr74, Karam C74, Chopra M74, Traub R74, Vu T75, Katzin L75, McClain T75, Harvey B75, Hart A75, Huynh K75, Beydoun S76, Chilingaryan A76, Doan V76, Droker B76, Gong H76, Karimi S76, Lin F76, McClain T76, Pokala K76, Shah A76, Tran A76, Akhter S76, Malekniazi A76, Tandan R77, Hehir M77, Waheed W77, Lucy S77, Weiss M78, Distad J78, Strom S78, Downing S78, Kim B78, Nowak R79, Dicapua D79, Keung B79, Kumar A79, Patwa H79, Robeson K79, Yang I79, Nye J79, Vu H79.

Author information

1
Department of Neurology, International University of Health and Welfare, Tokyo, Japan. Electronic address: murai@iuhw.ac.jp.
2
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: auzawa@chiba-u.jp.
3
Department of Neurology, National Hospital Organization Sendai Medical Center, Sendai, Japan.
4
Department of Neurology, Sapporo Medical University Hospital, Sapporo, Japan. Electronic address: toimai@sapmed.ac.jp.
5
Department of Neurology, Nagasaki University Hospital, Nagasaki, Japan.
6
Department of Neurology, Kindai University Hospital, Osaka, Japan.
7
Osaka Toneyama Medical Center, Toyonaka, Japan. Electronic address: meinosin@toneyama.go.jp.
8
Alexion Pharmaceuticals, Boston, MA, United States. Electronic address: fanny.obrien@alexion.com.
9
Formerly of Alexion Pharmaceuticals, Boston, MA, United States.
10
Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. Electronic address: kutsugi@s4.dion.ne.jp.
11
Instituto de Investigaciones Neurológicas Raúl Carrea (FLENI), Buenos Aires, Argentina.
12
Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
13
AZ Sint-Lucas - Campus Sint-Lucas, Ghent, Belgium.
14
Universitair Ziekenhuis Antwerpen, Edegem, Antwerp, Belgium.
15
Universitaire Ziekenhuizen Leuven (Neurology Department) and Laboratory of Neurobiology, Department of Neuroscience, Katholieke Universiteit Leuven and Center for Brain & Disease Research, Leuven, Belgium.
16
Universitaire Ziekenhuizen Leuven (Neurology Department), Leuven, Belgium.
17
Faculdade de Medicina do ABC, Santo André, Brazil.
18
Fundação Faculdade Regional de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil.
19
Universidade Federal de São Paulo [UNIFESP], São Paulo, Brazil.
20
University of Alberta Hospital, Edmonton, AB, Canada.
21
Fakultní nemocnice Ostrava, Ostrava, Czech Republic.
22
Všeobecná fakultní nemocnice v Praze, Praze, Czech Republic.
23
Århus Universitetshospital, Aarhus, Denmark.
24
Rigshospitalet, Copenhagen, Denmark.
25
Neuro NEO Oy, Turku, Finland.
26
Jahn Ferenc Dél-Pesti Kórház, Budapest, Hungary.
27
Azienda Ospedaliera Sant'Andrea - Università di Roma La Sapienza, Rome, Italy.
28
Azienda Ospedaliera Universitaria "Federico II", Italy.
29
Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
30
Policlinico Universitario Agostino Gemelli, Rome, Italy.
31
Chiba University Hospital, Chiba, Japan.
32
Department of Neurology, Kyushu University Hospital, Fukuoka, Japan.
33
Hanamaki General Hospital, Hanamaki, Japan.
34
Kinki University Hospital, Osaka, Japan.
35
Nagasaki University Hospital, Nagasaki, Japan.
36
National Hospital Organization Sendai Medical Center, Sendai, Japan.
37
Osaka University Hospital, Osaka, Japan.
38
Sapporo Medical University Hospital, Chuo-ku, Sapporo, Japan.
39
Academisch Medisch Centrum, Amsterdam-Zuidoost, Netherlands.
40
Hospital Universitari de Bellvitge, Barcelona, Spain.
41
Hospital Universitario La Paz, Madrid, Spain.
42
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
43
Neurology Department, Hospital Sant Pau, Universitat Autònoma de Barcelona, Spain.
44
Karolinska University Hospital, Stockholm, Sweden.
45
Dokuz Eylül University Faculty of Medicine, Izmir, Turkey.
46
Hacettepe University Faculty of Medicine, Ankara, Turkey.
47
Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
48
Ondokuz Mayis Univiversity Medical Faculty, Atakum/Samsun, Turkey.
49
King's College Hospital, London, UK.
50
Queen Elizabeth Neuroscience Centre, (Wellcome Trust CRF, University Hospitals Birmingham), Birmingham, UK.
51
The Walton Centre, Liverpool, UK.
52
Brigham and Women's Hospital, Boston, MA, USA.
53
University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
54
California Pacific Medical Center, San Francisco, CA, USA.
55
Carolinas HealthCare System, Charlotte, NC, USA.
56
Duke University Health System, Durham, NC, USA.
57
Indiana University, Indianapolis, IN, USA.
58
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
59
Lahey Hospital and Medical Center - Burlington, Burlington, MA, USA.
60
Las Vegas Clinic, Las Vegas, NV, USA.
61
Ohio State University Wexner Medical Center, Columbus, OH, USA.
62
Oregon Health and Science University, Portland, OR, USA.
63
Southern Illinois University School of Medicine, Springfield, IL, USA.
64
Stanford University School of Medicine, Stanford, CA, USA.
65
The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
66
UAB Medicine, Birmingham, AL, USA.
67
University of California-Irvine, Irvine, CA, USA.
68
University of California-San Francisco-Fresno, CA, USA.
69
University of Florida Health Jacksonville, Jacksonville, FL, USA.
70
University of Iowa Children's Hospital, Iowa City, IA, USA.
71
University of Kansas Medical Center, Kansas City, KS, USA.
72
University of Maryland Medical Center, Baltimore, MD, USA.
73
University of Miami Miller School of Medicine, Miami, FL, USA.
74
The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
75
University of South Florida, Tampa, FL, USA.
76
University of Southern California, Los Angeles, CA, USA.
77
University of Vermont Medical Center, Burlington, VT, USA.
78
University of Washington, Seattle, WA, USA.
79
Yale University, New Haven, CT, USA.

Abstract

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.65]); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68] and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.

KEYWORDS:

Eculizumab; Japanese patients; MG-ADL; MG-QoL15; Myasthenia gravis; Open-label extension study

PMID:
31698177
DOI:
10.1016/j.jns.2019.08.004
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