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73 results on '"Yuriko Nagane"'

1. Reappraisal of Oral Steroid Therapy for Myasthenia Gravis

Author

Tomihiro Imai, Shigeaki Suzuki, Yuriko Nagane, Akiyuki Uzawa, Hiroyuki Murai, and Kimiaki Utsugisawa

Subjects
myasthenia gravis, oral corticosteroids, treatment strategies, cross-sectional study, logistic regression analysis, Neurology. Diseases of the nervous system, RC346-429
Abstract

Treatment with oral corticosteroids at high doses with an escalation and de-escalation schedule is effective against myasthena gravis (MG). In fact, the use of corticosteroids has led to a reduction in mortality to below 10% after the 1960s. However, long-term use of oral steroids above a certain dosage level is known to cause a number of problems. In 2014, the Japanese clinical guidelines for MG proposed that the first goal in MG treatment (treatment target) should be set at minimal manifestations (MM) with oral prednisolone (PSL) 5 mg/day or below, and that treatment strategies should strive to attain this level as rapidly as possible. In 2015, a multicenter, cross-sectional study revealed that higher PSL dose and longer PSL treatment do not ensure better outcome. In the absence of good response, the PSL dose should be decreased by combining with modalities such as plasma exchange/plasmapheresis and intravenous immunoglobulin (fast-acting treatments). In 2018, we conducted a multicenter, cross-sectional study in a large population of Japanese patients with generalized MG, aiming to elucidate the correlation between oral PSL regimens and achievement of treatment goals. The ORs for low vs. high dose to achieve treatment goals at 1, 2, and 3 years were 10.4, 2.75, and 1.86, respectively, whereas the corresponding ORs for low vs. medium dose were 13.4, 3.99, and 4.92. Early combination with fast-acting therapy (OR 2.19 at 2 years, 2.11 at 3 years) or combination with calcineurin inhibitors (OR 2.09 at 2 years, 2.36 at 3 years) were also positively associated with achieving treatment goals. These results indicate that early combination of low-dose PSL regimens with other therapies is the key for early achievement of treatment goals in generalized MG. However, even with this regimen, ~35% of patients did not achieve the treatment target after 3 years. These results suggest the limitation of the current oral corticosteroid therapy. We need to develop new treatment options to increase the rate of satisfactory outcome.

Published
2020
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2. Effectiveness of early cycles of fast- acting treatment in generalised myasthenia gravis.

Author

Akiyuki Uzawa, Shigeaki Suzuki, Satoshi Kuwabara, Hiroyuki Akamine, Yosuke Onishi, Manato Yasuda, Yukiko Ozawa, Naoki Kawaguchi, Tomoya Kubota, Masanori P. Takaashi, Yasushi Suzuki, Genya Watanabe, Takashi Kimura, Takamichi Sugimoto, Makoto Samukawa, Naoya Minami, Masayuki Masuda, Shingo Konno, Yuriko Nagane, and Kimiaki Utsugisawa

Subjects
MYASTHENIA gravis, COVID-19 pandemic, DRUG side effects, NICOTINIC acetylcholine receptors, MEDICAL sciences
Published
2023
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3. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

Author

Mantegazza, R., Wolfe, G. I., Muppidi, S., Wiendl, H., Fujita, K. P., O'Brien, F. L., Booth, H. D. E., Howard, J. 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, 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, Brigitta, Szabadosne, Laszlo, Vecsei, Livia, Dezsi, Edina, Varga, Monika, Konyane, Antonini, Giovanni, Antonella Di Pasquale, Garibaldi, Matteo, Morino, Stefania, Troili, Fernanda, Fionda, Laura, Amelia, Evoli, Paolo Emilio Alboini, Valentina, D'Amato, Raffaele, Iorio, Inghilleri, Maurizio, Frasca, Vittorio, Elena, Giacomelli, Gori, MARIA CRISTINA, Diego, Lopergolo, Onesti, Emanuela, Maria, Gabriele, Francesco, Saccà, 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, Jun, Kawamata, Takashi, Murahara, Masaki, Saitoh, 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, 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, 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, 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, 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, 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, Liu, Ye, Lauren, Wheeler, Jasmine, Hewlett, Mollie, Vanderhook, Richard, Nowak, Daniel, Dicapua, Benison, Keung, Aditya, Kumar, Huned, Patwa, Kimberly, Robeson, Irene, Yang, Joan, Nye, and Hong, Vu

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Clinical Neurology, Antibodies, Monoclonal, Humanized, Placebo, Article, Antibodies, Post-intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Refractory, law, Internal medicine, Monoclonal, Myasthenia Gravis, Medicine and Health Sciences, Humans, Medicine, Humanized, Science & Technology, business.industry, Middle Aged, Eculizumab, Complement Inactivating Agents, Female, Treatment Outcome, EFFICACY, medicine.disease, Myasthenia gravis, Clinical trial, 030104 developmental biology, SAFETY, Neurosciences & Neurology, Neurology (clinical), business, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, 030217 neurology & neurosurgery, medicine.drug
Abstract

ObjectiveTo 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.MethodsPatients 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.ResultsA 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.ConclusionEculizumab 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.ClinicalTrials.gov IdentifierREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.Classification of EvidenceThis 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.

Published
2020
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4. Health‐related quality of life and treatment strategies in myasthenia gravis

Author

Kimiaki Utsugisawa, Tomihiro Imai, Akiyuki Uzawa, Shigeaki Suzuki, Hiroyuki Murai, and Yuriko Nagane

Subjects
Health related quality of life, medicine.medical_specialty, business.industry, Immunology, Neuroscience (miscellaneous), medicine.disease, Myasthenia gravis, Treatment targets, Immunology and Microbiology (miscellaneous), Treatment strategy, Medicine, Neurology (clinical), business, Intensive care medicine
Published
2020
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5. Anti‐striational antibodies: Expanding their clinical significance

Author

Shigeaki Suzuki, Kimiaki Utsugisawa, Hiroyuki Murai, Tomihiro Imai, Yuriko Nagane, Akiyuki Uzawa, and Jin Nakahara

Subjects
Thymoma, Myocarditis, biology, business.industry, Immunology, Neuroscience (miscellaneous), medicine.disease, Myasthenia gravis, Immunology and Microbiology (miscellaneous), biology.protein, medicine, Clinical significance, Neurology (clinical), Antibody, business
Published
2020
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6. Roles of cytokines and T cells in the pathogenesis of myasthenia gravis

Author

Kimiaki Utsugisawa, Manato Yasuda, Yukiko Ozawa, Shigeaki Suzuki, Tomihiro Imai, Akiyuki Uzawa, Yuriko Nagane, Satoshi Kuwabara, and Hiroyuki Murai

Subjects
0301 basic medicine, medicine.medical_treatment, Immunology, Reviews, Inflammation, T-Lymphocytes, Regulatory, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Myasthenia Gravis, medicine, Immunology and Allergy, Animals, Humans, Receptors, Cholinergic, B-cell activating factor, Autoantibodies, B-Lymphocytes, business.industry, Autoantibody, Interleukin, Receptor Protein-Tyrosine Kinases, medicine.disease, Myasthenia gravis, 030104 developmental biology, Cytokine, Cytokines, Th17 Cells, medicine.symptom, business, 030215 immunology
Abstract

Summary Myasthenia gravis (MG) is characterized by muscle weakness and fatigue caused by the presence of autoantibodies against the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK). Activated T, B and plasma cells, as well as cytokines, play important roles in the production of pathogenic autoantibodies and the induction of inflammation at the neuromuscular junction in MG. Many studies have focused on the role of cytokines and lymphocytes in anti-AChR antibody-positive MG. Chronic inflammation mediated by T helper type 17 (Th17) cells, the promotion of autoantibody production from B cells and plasma cells by follicular Th (Tfh) cells and the activation of the immune response by dysfunction of regulatory T (Treg) cells may contribute to the exacerbation of the MG pathogenesis. In fact, an increased number of Th17 cells and Tfh cells and dysfunction of Treg cells have been reported in patients with anti-AChR antibody-positive MG; moreover, the number of these cells was correlated with clinical parameters in patients with MG. Regarding cytokines, interleukin (IL)-17; a Th17-related cytokine, IL-21 (a Tfh-related cytokine), the B-cell-activating factor (BAFF; a B cell-related cytokine) and a proliferation-inducing ligand (APRIL; a B cell-related cytokine) have been reported to be up-regulated and associated with clinical parameters of MG. This review focuses on the current understanding of the involvement of cytokines and lymphocytes in the immunological pathogenesis of MG, which may lead to the development of novel therapies for this disease in the near future.

Published
2020

7. Reappraisal of Oral Steroid Therapy for Myasthenia Gravis

Author

Akiyuki Uzawa, Tomihiro Imai, Shigeaki Suzuki, Yuriko Nagane, Hiroyuki Murai, and Kimiaki Utsugisawa

Subjects
0301 basic medicine, medicine.medical_specialty, Cross-sectional study, medicine.medical_treatment, Review, oral corticosteroids, PSL, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, treatment strategies, medicine, Oral steroid therapy, cross-sectional study, lcsh:Neurology. Diseases of the nervous system, myasthenia gravis, business.industry, medicine.disease, logistic regression analysis, Myasthenia gravis, Calcineurin, Regimen, 030104 developmental biology, Neurology, Treatment strategy, Plasmapheresis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Treatment with oral corticosteroids at high doses with an escalation and de-escalation schedule is effective against myasthena gravis (MG). In fact, the use of corticosteroids has led to a reduction in mortality to below 10% after the 1960s. However, long-term use of oral steroids above a certain dosage level is known to cause a number of problems. In 2014, the Japanese clinical guidelines for MG proposed that the first goal in MG treatment (treatment target) should be set at minimal manifestations (MM) with oral prednisolone (PSL) 5 mg/day or below, and that treatment strategies should strive to attain this level as rapidly as possible. In 2015, a multicenter, cross-sectional study revealed that higher PSL dose and longer PSL treatment do not ensure better outcome. In the absence of good response, the PSL dose should be decreased by combining with modalities such as plasma exchange/plasmapheresis and intravenous immunoglobulin (fast-acting treatments). In 2018, we conducted a multicenter, cross-sectional study in a large population of Japanese patients with generalized MG, aiming to elucidate the correlation between oral PSL regimens and achievement of treatment goals. The ORs for low vs. high dose to achieve treatment goals at 1, 2, and 3 years were 10.4, 2.75, and 1.86, respectively, whereas the corresponding ORs for low vs. medium dose were 13.4, 3.99, and 4.92. Early combination with fast-acting therapy (OR 2.19 at 2 years, 2.11 at 3 years) or combination with calcineurin inhibitors (OR 2.09 at 2 years, 2.36 at 3 years) were also positively associated with achieving treatment goals. These results indicate that early combination of low-dose PSL regimens with other therapies is the key for early achievement of treatment goals in generalized MG. However, even with this regimen, ~35% of patients did not achieve the treatment target after 3 years. These results suggest the limitation of the current oral corticosteroid therapy. We need to develop new treatment options to increase the rate of satisfactory outcome.

Published
2020
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8. Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study

Author

Saiju Jacob, Hiroyuki Murai, Kimiaki Utsugisawa, Richard J. Nowak, Heinz Wiendl, Kenji P. Fujita, Fanny O’Brien, James F. Howard, Claudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Anneke van der Kooi, Marianne de Visser, Tamar Gibson, Seung Min Kim, JinWoo Jeong, Ha-Neul Jung, Yool-hee Kim, Hyung Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju Shin, Josep Gamez Carbonell, Pilar Sune, Maria Salvado Figueras, Gisela Gili, Gonzalo Mazuela, Fredrik Piehl, Albert Hietala, Lena Bjarbo, Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi Yilmaz, Yagmur Caliskan, Gulsah Orsel, Anthony Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine Amato, Shirli Toska, Jonathan McKinnon, Laura Haar, Naya McKinnon, Karan Alcon, Kaitlyn McKenna, Nadia Sattar, Kevin Daniels, Dennis Jeffery, Tahseen Mozaffar, Tiyonnoh Cash, Namita Goyal, Gulmohor Roy, Veena Mathew, Fatima Maqsood, Brian Minton, Charlene Hafer-Macko, Justin Kwan, Lindsay Zilliox, Karen Callison, Valerie Young, Beth DiSanzo, Kerry Naunton, 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, Krishna Polaka, Akshay Shah, Anh Tran, Salma Akhter, Ali Malekniazi, Rup Tandan, Michael Hehir, Waqar Waheed, Shannon Lucy, Tulio Bertorini, Thomas Arnold, Kendrick Hendersen, Rekha Pillai, Ye Liu, Lauren Wheeler, Jasmine Hewlett, and Mollie Vanderhook

Subjects
IVIg, 0301 basic medicine, medicine.medical_specialty, REGAIN, Subgroup analysis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, intravenous immunoglobulin, Internal medicine, medicine, In patient, Generalized myasthenia, RC346-429, Original Research, Pharmacology, myasthenia gravis, business.industry, Extension study, Eculizumab, medicine.disease, Myasthenia gravis, 030104 developmental biology, Neurology, eculizumab, Neurology (clinical), Neurology. Diseases of the nervous system, Open label, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab versus placebo. This subgroup analysis evaluated data from patients with a recent history of chronic intravenous immunoglobulin (IVIg) use before study entry. Methods: The subgroup comprised patients who had received IVIg at least four times in 1 year, with at least one IVIg treatment cycle during the 6 months before the first REGAIN study dose. Data from REGAIN and the OLE were analyzed. Response to eculizumab versus placebo was assessed using four validated, disease-specific measures. Incidences of exacerbations and safety endpoints were recorded. Results: The subgroup had similar patient and disease characteristics as the overall REGAIN population. Clinical assessments showed sustained eculizumab efficacy during REGAIN and the OLE over 18 months. Patients receiving placebo in REGAIN experienced rapid improvements in assessment scores when treated with eculizumab in the OLE. There was a lower rate of disease exacerbations with eculizumab than with placebo during REGAIN, and eculizumab was well tolerated. Conclusion: Eculizumab treatment, compared with placebo, results in meaningful clinical improvements and fewer disease exacerbations for patients who previously received chronic IVIg. Trial registration: REGAIN [ClinicalTrials.gov identifier: NCT01997229]; REGAIN open-label extension [ClinicalTrials.gov identifier: NCT02301624].

Published
2020

9. Significance of follow‐up thoracic imaging in myasthenia gravis

Author

Yuriko Nagane, Masakatsu Motomura, Kimiaki Utsugisawa, Hiroyuki Murai, Tomihiro Imai, and Shigeaki Suzuki

Subjects
0301 basic medicine, medicine.medical_specialty, Thoracic imaging, Thymoma, business.industry, Immunology, Neuroscience (miscellaneous), Cancer, medicine.disease, Myasthenia gravis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), medicine, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Published
2018
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10. Rationale for the clinical guidelines for myasthenia gravis in Japan

Author

Yuriko Nagane, Tomihiro Imai, Kimiaki Utsugisawa, Hiroyuki Murai, Shigeaki Suzuki, and Masakatsu Motomura

Subjects
Pediatrics, medicine.medical_specialty, Intravenous methylprednisolone, business.industry, General Neuroscience, medicine.medical_treatment, Disease, 030204 cardiovascular system & hematology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Myasthenia gravis, Thymectomy, Calcineurin, 03 medical and health sciences, 0302 clinical medicine, History and Philosophy of Science, Quality of life, medicine, In patient, Plasmapheresis, business, 030217 neurology & neurosurgery
Abstract

According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients' health-related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, using intravenous methylprednisolone infusion judiciously (often combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and effectively treating patients with an early, fast-acting treatment strategy. The early, fast-acting treatment strategy enables more frequent and earlier attainment of the initial goal than other strategies. Thymectomy is considered an option for treating nonthymomatous early-onset myasthenia gravis in patients with antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.

Published
2018
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11. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Author

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Mihoko Takada, Yamashita, Yumi, Yoshida, Seiko, Suzuki, Yasushi, Akiyama, Tetsuya, Narikawa, Koichi, Tsukita, Kenichi, Meguro, Fumie, Fukuda, Yusuke, Sato, Miwako, Matsuo, Hidenori, Fukudome, Takayasu, Gondo, Yuichiro, Maeda, Yasuhiro, Nagaishi, Akiko, Nakane, Shunya, Okubo, Yoshinori, Okumura, Meinoshin, Funaka, Soichiro, Kawamura, Tomohiro, Makamori, Masayuki, Takahashi, Masanori, Hasuike, Tomoya, Higuchi, Eriko, Kobayashi, Hisako, Osakada, Kaori, Taichi, Namie, Tsuda, Emiko, Hayashi, Takashi, Hisahara, Shin, Imai, Tomihiro, Kawamata, Jun, Murahara, Takashi, Saitoh, Masaki, Shimohama, Shun, Suzuki, Shuichiro, Yamamoto, Daisuke, Konno, Shingo, Imamura, Tomomi, Inoue, Masashi, Murata, Mayumi, Nakazora, Hiroshi, Nakayama, Ritsu, Ikeda, Yasuko, Ogawa, Miki, Shirane, Maoko, Kanda, Takashi, Kawai, Motoharu, Koga, Michiaki, Ogasawara, Junichi, Omoto, Masatoshi, Sano, Yasuteru, Arima, Hideki, Fukui, Sachie, Shimose, Shigemi, Shinozaki, Hirokazu, Watanabe, Masanori, Yoshikawa, Chieko, van der 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Edward, Quarles, Brandy, Smalley, Nicole, Amato, Anthony, Cochrane, Thoma, Salajegheh, Mohammed, Roe, Kristen, Amato, Katherine, Toska, Shirli, Wolfe, Gil, Silvestri, Nichola, Patrick, Kara, Zakalik, Karen, Katz, Jonathan, Miller, Robert, Engel, Marguerite, Bravver, Elena, Brooks, Benjamin, Plevka, Sarah, Burdette, Maryanne, Sanjak, Mohammad, Kramer, Megan, Nemeth, Joanne, Schommer, Clara, Juel, Vern, Guptill, Jeffrey, Hobson-Webb, Lisa, Beck, Kate, Carnes, Donna, Loor, John, Anderson, Amanda, Lange, Dale, Agopian, Eliz, Goldstein, Jonathan, Manning, Erin, Kaplan, Lindsay, Holzberg, Shara, Kassebaum, Nicole, Pascuzzi, Robert, Bodkin, Cynthia, Kincaid, John, Snook, Riley, Guinrich, Sandra, Micheels, Angela, Chaudhry, Vinay, Corse, Andrea, Mosmiller, Betsy, Ho, Doreen, Srinivasan, Jayashri, Vytopil, Michael, Ventura, Nichola, Scala, Stephanie, Carter, Cynthia, Donahue, Craig, Herbert, Carol, Weiner, Elaine, Mckinnon, Jonathan, Haar, Laura, Mckinnon, Naya, Alcon, Karan, Daniels, Kevin, Sattar, Nadia, Jeffery, Denni, Mckenna, Kaitlyn, Guidon, Amanda, David, William, Dheel, Christina, Levine-Weinberg, Mark, Nigro, Catherine, Simpson, Ericka, Appel, Stanley H, Lai, Eugene, Lay, Lui, Pleitez, Milvia, Halton, Sharon, Faigle, Casey, Thompson, Lisa, Sivak, Mark, Shin, Susan, Bratton, Joan, Jacobs, Daniel, Brown, Gavin, Bandukwala, Ibrez, Brown, Morri, Kane, Jennifer, Blount, Ira, Freimer, Miriam, Hoyle, J. Chad, Agriesti, Julie, Khoury, Julie, Marburger, Tessa, Kaur, Harpreet, Dimitrova, Diana, Mellion, Michelle, Sachs, George, Crabtree, Brigid, Keo, Roseann, Perez, Ele Kim, Taber, Sandra, Gilchrist, Jame, Andoin, Angela, Darnell, Taylor, Goyal, Neelam, Sakamuri, Sarada, So, Yuen T, Welsh, Lesly Welsh, Bhavaraju-Sanka, Ratna, Tobon Gonzalez, Alejandro, Jones, Floyd, Saklad, Amy, Nations, Sharon, Trivedi, Jaya, Hopkins, Steve, Kazamel, Mohamed, Alsharabati, Mohammad, Lu, Liang, Mumfrey-Thomas, Sandi, Woodall, Amy, Richman, David, Butters, Janelle, Lindsay, Molly, Mozaffar, Tahseen, Cash, Tiyonnoh, Goyal, Namita, Roy, Gulmohor, Mathew, Veena, Maqsood, Fatima, Minton, Brian, Jones, H. Jame, Rosenfeld, Jeffrey, Garcia, Rebekah, Garcia, Sonia, Echevarria, Laura, Pulley, Michael, Aranke, Shachie, Berger, Alan Ro, Shah, Jaimin, Shabbir, Yasmeen, Smith, Lisa, Varghese, Mary, Gutmann, Laurie, Gutmann, Ludwig, Swenson, Andrea, Olalde, Heena, Hafer-Macko, Charlene, Kwan, Justin, Zilliox, Lindsay, Callison, Karen, Disanzo, Beth, Naunton, Kerry, Bilsker, Martin, Sharma, Khema, Reyes, Eliana, Cooley, Anne, Michon, Sara-Claude, Steele, Julie, Karam, Chafic Karam, Chopra, Manisha, Bird, Shawn, Kaufman, Jacob, Gallatti, Nichole, Vu, Tuan, Katzin, Lara, Mcclain, Terry, Harvey, Brittany, Hart, Adam, Huynh, Kristin, Beydoun, Said, Chilingaryan, Amaiak, Droker, Brian, Lin, Frank, Shah, Akshay, Tran, Anh, Akhter, Salma, Malekniazi, Ali, Tandan, Rup, Hehir, Michael, Waheed, Waqar, Lucy, Shannon, Weiss, Michael, Distad, Jane, Downing, Sharon, Strom, Susan, Lisak, Robert, Bernitsas, Evanthia, Khan, Omar, Kumar Sriwastava, Shitiz, Tselis, Alexandro, Jia, Kelly, Bertorini, Tulio, Arnold, Thoma, Henderson, Kendrick, Pillai, Rekha, Liu, Ye, Wheeler, Lauren, Hewlett, Jasmine, Vanderhook, Mollie, Dicapua, Daniel, Keung, Benison, Kumar, Aditya, Patwa, Huned, Robeson, Kimberly, Nye, Joan, Vu, Hong, Howard, J, Utsugisawa, K, Benatar, M, Murai, H, Barohn, R, Illa, I, Jacob, S, Vissing, J, Burns, T, Kissel, J, Muppidi, S, Nowak, R, O'Brien, F, Wang, J, Mantegazza, R, and Bonanno, S

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, Drug Resistance, Adult, Aged, Antibodies, Monoclonal, Humanized, Autoantibodies, Double-Blind Method, Female, Humans, Middle Aged, Myasthenia Gravis, Receptors, Cholinergic, Outcome Assessment (Health Care), Severity of Illness Index, Neurology (clinical), law.invention, Complement inhibitor, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Clinical endpoint, Humanized, Cholinergic, education.field_of_study, Eculizumab, Autoantibodie, Myasthenia Gravi, Settore MED/26 - NEUROLOGIA, Human, medicine.drug, Meningitides, medicine.medical_specialty, Population, Placebo, Antibodies, 03 medical and health sciences, Internal medicine, medicine, education, business.industry, Surgery, Thymectomy, 030104 developmental biology, business, 030217 neurology & neurosurgery
Abstract

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Published
2017
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12. Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Author

Hiroyuki Murai, Akiyuki Uzawa, Yasushi Suzuki, Tomihiro Imai, Hirokazu Shiraishi, Hidekazu Suzuki, Meinoshin Okumura, Fanny O’Brien, Jing-Jing Wang, Kenji P. Fujita, Kimiaki Utsugisawa, 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'Hondt, Petra Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela 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, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Tomás Augusto Suriane Fialho, Luciana Renata Cubas Volpe, Luciana Souza Duca, Acary Souza Bulle Oliveira, Ana Carolina Amaral Andrade, Marcelo Annes, Liene Duarte Silva, Valeria Cavalcante Lino, Wladimir Pinto, Natália Assis, Fernanda Carrara, Carolina Miranda, Iandra Souza, Patricia Fernandes, Zaeem Siddiqi, Cecile Phan, Jeffrey Narayan, Derrick Blackmore, Ashley Mallon, Rikki Roderus, Elizabeth Watt, 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 Eralinna, Mikko Laaksonen, Olli Oksaranta, Tuula Harrison, Jaana Eriksson, Csilla Rozsa, Melinda Horvath, Gabor Lovas, Judit Matolcsi, Gyorgyi Szabo, Gedeonne Jakab, Brigitta Szabadosne, Giovanni Antonini, Antonella Di Pasquale, Matteo Garibaldi, Stefania Morino, Fernanda Troili, Laura Fionda, Allessandro Filla, Teresa Costabile, Enrico Marano, Francesco Saccà, Angiola Fasanaro, Angela Marsili, Giorgia Puorro, Renato Mantegazza, Carlo Antozzi, Silvia Bonanno, Giorgia Camera, Alberta Locatelli, Lorenzo Maggi, Maria Pasanisi, Angela Campanella, Amelia Evoli, Paolo Emilio Alboini, Valentina D'Amato, Raffaele Iorio, Tetsuya Kanai, Naoki Kawaguchi, Masahiro Mori, Yoko Kaneko, Akiko Kanzaki, Eri Kobayashi, Katsuhisa Masaki, Dai Matsuse, Takuya Matsushita, Taira Uehara, Misa Shimpo, Maki Jingu, Keiko Kikutake, Yumiko Nakamura, Yoshiko Sano, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Miyuki Morikawa, Makoto Samukawa, Sachiko Kamakura, Eriko Miyawaki, Teiichiro Mitazaki, Masakatsu Motomura, Akihiro Mukaino, Shunsuke Yoshimura, Shizuka Asada, Seiko Yoshida, Shoko Amamoto, Tomomi Kobashikawa, Megumi Koga, Yasuko Maeda, Kazumi Takada, Mihoko Takada, Masako Tsurumaru, Yumi Yamashita, Tetsuya Akiyama, Koichi Narikawa, Ohito Tano, Kenichi Tsukita, Rikako Kurihara, Fumie Meguro, Yusuke Fukuda, Miwako Sato, Soichiro Funaka, Tomohiro Kawamura, Masayuki Makamori, Masanori Takahashi, Namie Taichi, Tomoya Hasuike, Eriko Higuchi, Hisako Kobayashi, Kaori Osakada, Emiko Tsuda, Shun Shimohama, Takashi Hayashi, Shin Hisahara, Jun Kawamata, Takashi Murahara, Masaki Saitoh, 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, Carlos Casasnovas, Maria Antonia Alberti Aguilo, Christian Homedes-Pedret, Natalia Julia Palacios, Laura Diez Porras, Valentina Velez Santamaria, Ana Lazaro, Exuperio Diez Tejedor, Pilar Gomez Salcedo, Mireya Fernandez-Fournier, Pedro Lopez Ruiz, Francisco Javier Rodriguez de Rivera, Maria Sastre, Josep Gamez, Pilar Sune, Maria Salvado, Gisela Gili, Gonzalo Mazuela, Isabel Illa, Elena Cortes Vicente, Jordi Diaz-Manera, Luis Antonio Querol Gutierrez, Ricardo Rojas Garcia, Nuria Vidal, Elisabet Arribas-Ibar, 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, Claire Brown, Amna Shah, Sivakumar Sathasivam, Heike Arndt, Debbie Davies, Dave Watling, Anthony Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine Amato, Shirli Toska, Gil Wolfe, Nicholas Silvestri, Kara Patrick, Karen Zakalik, Jonathan Katz, Robert Miller, Marguerite Engel, Dallas Forshew, Elena Bravver, Benjamin Brooks, Sarah Plevka, Maryanne Burdette, Scott Cunningham, Mohammad Sanjak, Megan Kramer, Joanne Nemeth, Clara Schommer, Scott Tierney, 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, Stephanie Scala, Cynthia Carter, Craig Donahue, Carol Herbert, 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 Andoin, Taylor Darnell, Laura Golden, Barbara Lokaitis, Jenna Seelback, Srikanth Muppidi, Neelam Goyal, Sarada Sakamuri, Yuen T. So, Shirley Paulose, Sabrina Pol, Lesly Welsh, Ratna Bhavaraju-Sanka, Alejandro Tobon Gonzales, Lorraine Dishman, Floyd Jones, Anna Gonzalez, Patricia Padilla, Amy Saklad, Marcela Silva, 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, 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, James Howard Jr, Manisha Chopra, Rebecca Traub, 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, Krishna Pokala, 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, Richard Nowak, Daniel Dicapua, Benison Keung, Aditya Kumar, Huned Patwa, Kimberly Robeson, Irene Yang, Joan Nye, Hong Vu, H., Murai, A., Uzawa, Y., Suzuki, T., Imai, H., Shiraishi, H., Suzuki, M., Okumura, F., O'Brien, J. -J., Wang, K. P., Fujita, K., Utsugisawa, Gabriel Mazia 11, Claudio, Wilken 11, Miguel, Barroso 11, Fabio, Saba 11, Juliet, Rugiero 12, Marcelo, Bettini 12, Mariela, Chaves 12, Marcelo, Vidal 12, Gonzalo, Dalila Garcia 12, Alejandra, De Bleecker 13, Jan, Van den Abeele 13, Guy, de Koning 13, Kathy, De Mey 13, Katrien, Mercelis 14, Rudy, Mahieu 14, Délphine, Wagemaekers 14, Linda, Van Damme 15, Philip, Depreitere 16, Annelie, Schotte 16, Caroline, Smetcoren 16, Charlotte, Stevens 16, Olivier, Van Daele 16, Sien, Vandenbussche 16, Nicola, Vanhee 16, Annelie, Verjans 16, Sarah, Vynckier 16, Jan, D'Hondt 16, Ann, Tilkin 16, Petra, Alves de Siqueira Carvalho 17, Alzira, Dias Brockhausen 17, Igor, Feder 17, David, Ambrosio 17, Daniel, César 17, Pamela, Paula Melo 17, Ana, Martins Ribeiro 17, Renata, Rocha 17, Rosana, Bezerra Rosa 17, Bruno, Veiga 17, Thabata, Augusto da Silva 17, Luiz, Santos Engel 17, Murilo, Gonçalves Geraldo 17, Jordana, da Penha Ananias Morita 18, Maria, Nogueira Coelho 18, Erica, Paiva 18, Gabriel, Pozo 18, Marina, Prando 18, Natalia, Dada Martineli Torres 18, Debora, Fernanda Butinhao 18, Cristiani, Duran 18, Gustavo, Cristina Gomes da Silva 18, Tamire, Otavio Maia Gonçalves 18, Luiz, Eduardo Pazetto 18, Luca, Augusto Suriane Fialho 18, Tomá, Renata Cubas Volpe 18, Luciana, Souza Duca 18, Luciana, Souza Bulle Oliveira 19, Acary, Carolina Amaral Andrade 19, Ana, Annes 19, Marcelo, Duarte Silva 19, Liene, Cavalcante Lino 19, Valeria, Pinto 19, Wladimir, Assis 19, Natália, Carrara 19, Fernanda, Miranda 19, Carolina, Souza 19, Iandra, Fernandes 19, Patricia, Siddiqi 20, Zaeem, Phan 20, Cecile, Narayan 20, Jeffrey, Blackmore 20, Derrick, Mallon 20, Ashley, Roderus 20, Rikki, Watt 20, Elizabeth, Junkerova 21, Jana, Kurkova 21, Barbora, Reguliova 21, Katarina, Zapletalova 21, Olga, Pitha 22, Jiri, Novakova 22, Iveta, Tyblova 22, Michaela, Jurajdova 22, Ivana, Wolfova 22, Marcela, Andersen 23, Henning, Harbo 23, Thoma, Vinge 23, Lotte, Krogh 23, Susanne, Mogensen 23, Anita, Vissing 24, John, Højgaard 24, Joan, Witting 24, Nanna, Mette Ostergaard Autzen 24, Anne, Pedersen 24, Jane, Eralinna 25, Juha-Pekka, Laaksonen 25, Mikko, Oksaranta 25, Olli, Harrison 25, Tuula, Eriksson 25, Jaana, Rozsa 26, Csilla, Horvath 26, Melinda, Lovas 26, Gabor, Matolcsi 26, Judit, Szabo 26, Gyorgyi, Jakab 26, Gedeonne, Szabadosne 26, Brigitta, Antonini 27, Giovanni, Di Pasquale 27, Antonella, Garibaldi 27, Matteo, Morino 27, Stefania, Troili 27, Fernanda, Fionda 27, Laura, Filla, Allessandro, Costabile, Teresa, Marano, Enrico, Sacca', Francesco, Fasanaro, Angiola, Marsili, Angela, Puorro, Giorgia, Mantegazza 29, Renato, Antozzi 29, Carlo, Bonanno 29, Silvia, Camera 29, Giorgia, Locatelli 29, Alberta, Maggi 29, Lorenzo, Pasanisi 29, Maria, Campanella 29, Angela, Evoli 30, Amelia, Emilio Alboini 30, Paolo, D'Amato 30, Valentina, Iorio 30, Raffaele, Kanai 31, Tetsuya, Kawaguchi 31, Naoki, Mori 31, Masahiro, Kaneko 31, Yoko, Kanzaki 31, Akiko, Kobayashi 31, Eri, Masaki 32, Katsuhisa, Matsuse 32, Dai, Matsushita 32, Takuya, Uehara 32, Taira, Shimpo 32, Misa, Jingu 32, Maki, Kikutake 32, Keiko, Nakamura 32, Yumiko, Sano 32, Yoshiko, Nagane 33, Yuriko, Kamegamori 33, Ikuko, Tsuda 33, Tomoko, Fujii 33, Yuko, Futono 33, Kazumi, Ozawa 33, Yukiko, Mizugami 33, Aya, Saito 33, Yuka, Morikawa 34, Miyuki, Samukawa 34, Makoto, Kamakura 34, Sachiko, Miyawaki 34, Eriko, Mitazaki 35, Teiichiro, Motomura 35, Masakatsu, Mukaino 35, Akihiro, Yoshimura 35, Shunsuke, Asada 35, Shizuka, Yoshida 35, Seiko, Amamoto 35, Shoko, Kobashikawa 35, Tomomi, Koga 35, Megumi, Maeda 35, Yasuko, Takada 35, Kazumi, Takada 35, Mihoko, Tsurumaru 35, Masako, Yamashita 35, Yumi, Akiyama 36, Tetsuya, Narikawa 36, Koichi, Tano 36, Ohito, Tsukita 36, Kenichi, Kurihara 36, Rikako, Meguro 36, Fumie, Fukuda 36, Yusuke, Sato 36, Miwako, Funaka 37, Soichiro, Kawamura 37, Tomohiro, Makamori 37, Masayuki, Takahashi 37, Masanori, Taichi 37, Namie, Hasuike 37, Tomoya, Higuchi 37, Eriko, Kobayashi 37, Hisako, Osakada 37, Kaori, Tsuda 38, Emiko, Shimohama 38, Shun, Hayashi 38, Takashi, Hisahara 38, Shin, Kawamata 38, Jun, Murahara 38, Takashi, Saitoh 38, Masaki, Suzuki 38, Shuichiro, Yamamoto 38, Daisuke, Ishiyama 38, Yoko, Ishiyama 38, Naoko, Noshiro 38, Mayuko, Takeyama 38, Rumi, Uwasa 38, Kaori, Yasuda 38, Ikuko, van der Kooi 39, Anneke, de Visser 39, Marianne, Gibson 39, Tamar, Casasnovas 40, Carlo, Antonia Alberti Aguilo 40, Maria, Homedes-Pedret 40, Christian, Julia Palacios 40, Natalia, Diez Porras 40, Laura, Velez Santamaria 40, Valentina, Lazaro 40, Ana, Diez Tejedor 41, Exuperio, Gomez Salcedo 41, Pilar, Fernandez-Fournier 41, Mireya, Lopez Ruiz 41, Pedro, Javier Rodriguez de Rivera 41, Francisco, Sastre 41, Maria, Gamez 42, Josep, Sune 42, Pilar, Salvado 42, Maria, Gili 42, Gisela, Mazuela 42, Gonzalo, Illa 43, Isabel, Cortes Vicente 43, Elena, Diaz-Manera 43, Jordi, Antonio Querol Gutierrez 43, Lui, Rojas Garcia 43, Ricardo, Vidal 43, Nuria, Arribas-Ibar 43, Elisabet, Piehl 44, Fredrik, Hietala 44, Albert, Bjarbo 44, Lena, Sengun 45, Ihsan, Meherremova 45, Arzu, Ozcelik 45, Pinar, Balkan 45, Bengu, Tuga 45, Celal, Ugur 45, Muzeyyen, Erdem-Ozdamar 46, Sevim, Ebru Bekircan-Kurt 46, Can, Pinar Acar 46, Nazire, Yilmaz 46, Ezgi, Caliskan 46, Yagmur, Orsel 46, Gulsah, Efendi 47, Husnu, Aydinlik 47, Seda, Cavus 47, Hakan, Kutlu 47, Ayse, Becerikli 47, Gulsah, Semiz 47, Cansu, Tun 47, Ozlem, Terzi 48, Murat, Dogan 48, Baki, Kazim Onar 48, Musa, Sen 48, Sedat, Kirbas Cavdar 48, Tugce, Veske 48, Adife, Norwood 49, Fiona, Dimitriou 49, Aikaterini, Gollogly 49, Jakit, Mahdi-Rogers 49, Mohamed, Seddigh 49, Arshira, Sokratous 49, Gianni, Maier 49, Gal, Sohail 49, Faisal, Jacob 50, Saiju, Sadalage 50, Girija, Torane 50, Pravin, Brown 50, Claire, Shah 50, Amna, Sathasivam 51, Sivakumar, Arndt 51, Heike, Davies 51, Debbie, Watling 51, Dave, Amato 52, Anthony, Cochrane 52, Thoma, Salajegheh 52, Mohammed, Roe 52, Kristen, Amato 52, Katherine, Toska 52, Shirli, Wolfe 53, Gil, Silvestri 53, Nichola, Patrick 53, Kara, Zakalik 53, Karen, Katz 54, Jonathan, Miller 54, Robert, Engel 54, Marguerite, Forshew 54, Dalla, Bravver 55, Elena, Brooks 55, Benjamin, Plevka 55, Sarah, Burdette 55, Maryanne, Cunningham 55, Scott, Sanjak 55, Mohammad, Kramer 55, Megan, Nemeth 55, Joanne, Schommer 55, Clara, Tierney 55, Scott, Juel 56, Vern, Guptill 56, Jeffrey, Hobson-Webb 56, Lisa, Massey 56, Janice, Beck 56, Kate, Carnes 56, Donna, Loor 56, John, Anderson 56, Amanda, Pascuzzi 57, Robert, Bodkin 57, Cynthia, Kincaid 57, John, Snook 57, Riley, Guingrich 57, Sandra, Micheels 57, Angela, Chaudhry 58, Vinay, Corse 58, Andrea, Mosmiller 58, Betsy, Kelley 58, Andrea, Ho 59, Doreen, Srinivasan 59, Jayashri, Vytopil 59, Michal, Jara 59, Jordan, Ventura 59, Nichola, Scala 59, Stephanie, Carter 59, Cynthia, Donahue 59, Craig, Herbert 59, Carol, Weiner 59, Elaine, Alam 59, Sharmeen, McKinnon 60, Jonathan, Haar 60, Laura, McKinnon 60, Naya, Alcon 60, Karan, McKenna 60, Kaitlyn, Sattar 60, Nadia, Daniels 60, Kevin, Jeffery 60, Denni, Freimer 61, Miriam, Chad Hoyle 61, Joseph, Kissel 61, John, Agriesti 61, Julie, Chelnick 61, Sharon, Mezache 61, Louisa, Pineda 61, Colleen, Muharrem 61, Filiz, Karam 62, Chafic, Khoury 62, Julie, Marburger 62, Tessa, Kaur 62, Harpreet, Dimitrova 62, Diana, Gilchrist 63, Jame, Agrawal 63, Brajesh, Elsayed 63, Mona, Kohlrus 63, Stephanie, Andoin 63, Angela, Darnell 63, Taylor, Golden 63, Laura, Lokaitis 63, Barbara, Seelback 63, Jenna, Muppidi 64, Srikanth, Goyal 64, Neelam, Sakamuri 64, Sarada, T So 64, Yuen, Paulose 64, Shirley, Pol 64, Sabrina, Welsh 64, Lesly, Bhavaraju-Sanka 65, Ratna, Tobon Gonzales 65, Alejandro, Dishman 65, Lorraine, Jones 65, Floyd, Gonzalez 65, Anna, Padilla 65, Patricia, Saklad 65, Amy, Silva 65, Marcela, Kazamel 66, Mohamed, Alsharabati 66, Mohammad, Lu 66, Liang, Nozaki 66, Kenkichi, Mumfrey-Thomas 66, Sandi, Woodall 66, Amy, Mozaffar 67, Tahseen, Cash 67, Tiyonnoh, Goyal 67, Namita, Roy 67, Gulmohor, Mathew 67, Veena, Maqsood 67, Fatima, Minton 67, Brian, James Jones 68, H, Rosenfeld 68, Jeffrey, Garcia 68, Rebekah, Echevarria 68, Laura, Garcia 68, Sonia, Pulley 69, Michael, Aranke 69, Shachie, Ross Berger 69, Alan, Shah 69, Jaimin, Shabbir 69, Yasmeen, Smith 69, Lisa, Varghese 69, Mary, Gutmann 70, Laurie, Gutmann 70, Ludwig, Jerath 70, Nivedita, Nance 70, Christopher, Swenson 70, Andrea, Olalde 70, Heena, Kressin 70, Nicole, Sieren 70, Jeri, Barohn 71, Richard, Dimachkie 71, Mazen, Glenn 71, Melanie, McVey 71, April, Pasnoor 71, Mamatha, Statland 71, Jeffery, Wang 71, Yunxia, Liu 71, Tina, Emmons 71, Kelley, Jenci 71, Nicole, Locheke 71, Jerry, Fondaw 71, Alex, Johns 71, Kathryn, Rico 71, Gabrielle, Walsh 71, Maureen, Herbelin 71, Laura, Hafer-Macko 72, Charlene, Kwan 72, Justin, Zilliox 72, Lindsay, Callison 72, Karen, Young 72, Valerie, DiSanzo 72, Beth, Naunton 72, Kerry, Benatar 73, Michael, Bilsker 73, Martin, Sharma 73, Khema, Cooley 73, Anne, Reyes 73, Eliana, Michon 73, Sara-Claude, Sheldon 73, Danielle, Steele 73, Julie, Howard Jr 74, Jame, Karam 74, Chafic, Chopra 74, Manisha, Traub 74, Rebecca, Vu 75, Tuan, Katzin 75, Lara, McClain 75, Terry, Harvey 75, Brittany, Hart 75, Adam, Huynh 75, Kristin, Beydoun 76, Said, Chilingaryan 76, Amaiak, Doan 76, Victor, Droker 76, Brian, Gong 76, Hui, Karimi 76, Sanaz, Lin 76, Frank, McClain 76, Terry, Pokala 76, Krishna, Shah 76, Akshay, Tran 76, Anh, Akhter 76, Salma, Malekniazi 76, Ali, Tandan 77, Rup, Hehir 77, Michael, Waheed 77, Waqar, Lucy 77, Shannon, Weiss 78, Michael, Distad 78, Jane, Strom 78, Susan, Downing 78, Sharon, Kim 78, Bryan, Nowak 79, Richard, Dicapua 79, Daniel, Keung 79, Benison, Kumar 79, Aditya, Patwa 79, Huned, Robeson 79, Kimberly, Yang 79, Irene, Nye 79, Joan, and Hong Vu

Subjects
Male, Pediatrics, Myasthenia gravi, Open-label extension study, Complement inhibitor, 0302 clinical medicine, Quality of life, Japan, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Myasthenia gravis, education.field_of_study, MG-ADL, Japanese patient, Eculizumab, Middle Aged, HLA, MG-QoL15, Treatment Outcome, Neurology, Female, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, medicine.drug, Adult, medicine.medical_specialty, Population, Clinical Neurology, Subgroup analysis, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Refractory, Asian People, Myasthenia Gravis, Humans, education, Aged, Science & Technology, business.industry, Neurosciences, medicine.disease, Complement Inactivating Agents, Japanese patients, ONSET, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
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. ispartof: JOURNAL OF THE NEUROLOGICAL SCIENCES vol:407 ispartof: location:Netherlands status: published

Published
2019

13. Treatment of myasthenia gravis patients with calcineurin inhibitors in Japan: A retrospective analysis of outcomes

Author

Tomihiro Imai, Masayuki Masuda, Masakatsu Motomura, Yuriko Nagane, Shigeaki Suzuki, Shingo Konno, and Kimiaki Utsugisawa

Subjects
medicine.medical_specialty, Dose, business.industry, Immunology, Neuroscience (miscellaneous), Disease, medicine.disease, calcineurin inhibitors, Myasthenia gravis, Tacrolimus, Surgery, myasthenia, Calcineurin, Immunology and Microbiology (miscellaneous), Quality of life, quality of life, Internal medicine, Prednisolone, medicine, Retrospective analysis, Neurology (clinical), cyclosporine, business, tacrolimus, medicine.drug
Abstract

Objectives Calcineurin inhibitors (CNI) are approved for the treatment of myasthenia gravis (MG) in Japan. However, the extent to which CNI have been effective remains unclear. Here we report data regarding CNI use and outcomes of MG. Methods We evaluated 640 consecutive MG patients by a multicenter survey. Patients not receiving any immune treatment were excluded, and cross-sectional and retrospective data of 515 patients receiving immune treatment with (n = 312) or without (n = 203) CNI were analyzed. Results Compared with patients treated without CNI, those treated with CNI had a higher frequency of MG Foundation of America Class III-V and higher severity disease at the worst clinical condition, and also had current higher severity, worse quality of life and higher daily doses of prednisolone, despite taking equivalent prednisolone dosages during the course of treatment. Achieving a treatment target was less frequent in the group treated with CNI. Onset age was not different between the two groups. Duration before CNI use after starting corticosteroids was 4.4 ± 6.3 years. Among those treated with CNI, late-onset MG patients achieved a more favorable current condition than did those with early-onset and thymoma-associated MG, whereas there was no such difference without CNI treatment. Conclusions CNI were given to severely ill MG patients with no attempt to select those more likely to respond, and failed to exert a strong impact on MG therapy. CNI should be given aggressively to patients with factors known to enhance susceptibility to these drugs, such as higher age at onset and early-stage disease., Clinical and Experimental Neuroimmunology, 6(2), pp.195-200; 2015

Published
2015

14. Oral corticosteroid therapy and present disease status in myasthenia gravis

Author

Yuriko Nagane, Kimiaki Utsugisawa, Yasushi Suzuki, Emiko Tsuda, Masayuki Masuda, Shingo Konno, Hiroyuki Murai, Tomihiro Imai, Shunya Nakane, Norihiro Suzuki, Shigeaki Suzuki, and Kazuo Fujihara

Subjects
medicine.medical_specialty, Disease status, Physiology, Cross-sectional study, business.industry, medicine.medical_treatment, Odds ratio, medicine.disease, PSL, Gastroenterology, Myasthenia gravis, Surgery, Cellular and Molecular Neuroscience, Corticosteroid therapy, Physiology (medical), Internal medicine, medicine, Prednisolone, Plasmapheresis, Neurology (clinical), business, medicine.drug
Abstract

Introduction: The aim of this study was to elucidate the effectiveness of oral prednisolone (PSL) according to dosing regimen in 472 patients with myasthenia gravis (MG). Methods: We compared the clinical characteristics and PSL treatment between 226 patients who achieved minimal manifestations (MM) or better and 246 patients who remained improved (I) or worsened, according to the MG Foundation of America postintervention status. Results: Achievement of MM or better at peak PSL dose (odds ratio 12.25, P

Published
2015
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15. Rationale for the clinical guidelines for myasthenia gravis in Japan

Author

Hiroyuki, Murai, Kimiaki, Utsugisawa, Yuriko, Nagane, Shigeaki, Suzuki, Tomihiro, Imai, and Masakatsu, Motomura

Subjects
Japan, Prednisolone, Calcineurin Inhibitors, Myasthenia Gravis, Quality of Life, Humans, Receptors, Cholinergic, Thymectomy, Methylprednisolone, Antibodies, Cholinergic Antagonists, Immunosuppressive Agents
Abstract

According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients' health-related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, using intravenous methylprednisolone infusion judiciously (often combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and effectively treating patients with an early, fast-acting treatment strategy. The early, fast-acting treatment strategy enables more frequent and earlier attainment of the initial goal than other strategies. Thymectomy is considered an option for treating nonthymomatous early-onset myasthenia gravis in patients with antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.

Published
2017

16. Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan

Author

Kimiaki Utsugisawa, Tetsuya Akaishi, Emiko Tsuda, N. Minami, Masayuki Masuda, Masashi Aoki, Shingo Konno, Hidekazu Suzuki, Yasushi Suzuki, Naoki Kawaguchi, Tomihiro Imai, Akiyuki Uzawa, Yuriko Nagane, and Hiroyuki Murai

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, medicine.drug_class, Prednisolone, Administration, Oral, PSL, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Japan, Internal medicine, Myasthenia Gravis, medicine, calcineurin inhibitor, Humans, Glucocorticoids, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, business.industry, Dosing regimen, Middle Aged, medicine.disease, Prognosis, logistic regression analysis, Myasthenia gravis, Surgery, Calcineurin, Psychiatry and Mental health, Regimen, 030104 developmental biology, Cross-Sectional Studies, Treatment Outcome, Neuromuscular, Corticosteroid, Drug Therapy, Combination, Female, Neurology (clinical), business, postintervention status, 030217 neurology & neurosurgery, medicine.drug
Abstract

ObjectiveWe examined the correlation between the dosing regimen of oral prednisolone (PSL) and the achievement of minimal manifestation status or better on PSL ≤5 mg/day lasting >6 months (the treatment target) in patients with generalised myasthenia gravis (MG).MethodsWe classified 590 patients with generalised MG into high-dose (n=237), intermediate-dose (n=187) and low-dose (n=166) groups based on the oral PSL dosing regimen, and compared the clinical characteristics, previous treatments other than PSL and prognosis between three groups. The effect of oral PSL dosing regimen on the achievement of the treatment target was followed for 3 years of treatment.ResultsTo achieve the treatment target, ORs for low-dose versus high-dose regimen were 10.4 (PConclusionA low-dose PSL regimen with early combination of other treatment options may ensure earlier achievement of the treatment target in generalised MG.

Published
2017

17. Social disadvantages associated with myasthenia gravis and its treatment: a multicentre cross-sectional study

Author

Akiyuki Uzawa, Yuriko Nagane, Daisuke Yamamoto, Naoki Kawaguchi, Hiroyuki Murai, Shingo Konno, Tomihiro Imai, Emiko Tsuda, Hidekazu Suzuki, Yasushi Suzuki, Masashi Aoki, N. Minami, Masayuki Masuda, Kimiaki Utsugisawa, and Tetsuya Kanai

Subjects
Male, Pediatrics, Cross-sectional study, Severity of Illness Index, 0302 clinical medicine, Quality of life, Japan, Surveys and Questionnaires, 030212 general & internal medicine, Young adult, Depression (differential diagnoses), Aged, 80 and over, Depression, Medical record, General Medicine, Middle Aged, Neurology, MENTAL HEALTH, Prednisolone, Income, Female, SOCIAL MEDICINE, medicine.drug, Adult, medicine.medical_specialty, 03 medical and health sciences, Social support, Young Adult, Severity of illness, Myasthenia Gravis, medicine, Humans, Aged, Psychiatric Status Rating Scales, business.industry, Research, Social Support, Cross-Sectional Studies, Logistic Models, Unemployment, Multivariate Analysis, Physical therapy, Quality of Life, business, 030217 neurology & neurosurgery
Abstract

Objectives To clarify the social disadvantages associated with myasthenia gravis (MG) and examine associations with its disease and treatment. Design Cross-sectional study. Setting and participants We evaluated 917 consecutive cases of established MG seen at 13 neurological centres in Japan over a short duration. Outcome measures All patients completed a questionnaire on social disadvantages resulting from MG and its treatment and a 15-item MG-specific quality of life scale at study entry. Clinical severity at the worst condition was graded according to the MG Foundation of America classification, and that at the current condition was determined according to the quantitative MG score and MG composite. Maximum dose and duration of dose ≥20 mg/day of oral prednisolone during the disease course were obtained from the patients9 medical records. Achievement of the treatment target (minimal manifestation status with prednisolone at ≤5 mg/day) was determined at 1, 2 and 4 years after starting treatment and at study entry. Results We found that 27.2% of the patients had experienced unemployment, 4.1% had been unwillingly transferred and 35.9% had experienced a decrease in income, 47.1% of whom reported that the decrease was ≥50% of their previous total income. In addition, 49.0% of the patients reported feeling reduced social positivity. Factors promoting social disadvantages were severity of illness, dose and duration of prednisolone, long-term treatment, and a depressive state and change in appearance after treatment with oral steroids. Early achievement of the treatment target was a major inhibiting factor. Conclusions Patients with MG often experience unemployment, unwilling job transfers and a decrease in income. In addition, many patients report feeling reduced social positivity. To inhibit the social disadvantages associated with MG and its treatment, greater focus needs to be placed on helping patients with MG resume a normal lifestyle as soon as possible by achieving the treatment target.

Published
2017

18. Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools

Author

Tomohiro Makino, Ryuichi Nakamura, Yuriko Nagane, Maki Terakawa, Jyoji Yamate, Satoshi Muneoka, Kimiaki Utsugisawa, Masakatsu Motomura, and Kazuhiro Nagahira

Subjects
0301 basic medicine, Nicotinic Acetylcholine Receptors, Adoptive cell transfer, lcsh:Medicine, Receptors, Nicotinic, Biochemistry, Binding Analysis, Database and Informatics Methods, Cellular types, Receptor, lcsh:Science, B-Lymphocytes, Multidisciplinary, biology, Chemistry, Immune cells, Antibodies, Monoclonal, Antibody Isotype Determination, Flow Cytometry, Adoptive Transfer, Nicotinic acetylcholine receptor, medicine.anatomical_structure, White blood cells, Single-Cell Analysis, Antibody, Cell Binding Assay, Sequence Analysis, Research Article, Signal Transduction, Blood cells, Transmembrane Receptors, Bioinformatics, T cell, Primary Cell Culture, Immunology, Research and Analysis Methods, Antibody-producing cells, Neuromuscular junction, 03 medical and health sciences, Amino Acid Sequence Analysis, Myasthenia Gravis, medicine, Animals, Humans, Molecular Biology Techniques, Molecular Biology, Chemical Characterization, B cell, Autoantibodies, Medicine and health sciences, B cells, Hybridomas, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, Memory B cells, medicine.disease, Molecular biology, Myasthenia gravis, Rats, Protein Subunits, 030104 developmental biology, Animal cells, Acetylcholine Receptors, Immunologic Techniques, biology.protein, lcsh:Q, Cloning
Abstract

The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization. By applying a single cell technology and novel high-throughput cell-based binding assays, we identified peripheral B cells that produce pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced by individual peripheral B cells generally exhibited low binding affinity for the α-subunit of the nAChR and great sequence diversity, a small fraction of these antibodies bound with high affinity to native-structured nAChRs on cell surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for binding to the human nAChR and thus considered to recognize the main immunogenic region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents and presumably in humans.These findings suggest that B cells in peripheral blood may impact MG pathogenicity. Our methodology can be applied not only to validate pathogenic Abs as molecular target of MG treatment, but also to discover and analyze Ab production systems in other human diseases.

Published
2017

19. Japanese cases of neuromyelitis optica spectrum disorder associated with myasthenia gravis and a review of the literature

Author

Masayuki Masuda, Hiroya Utsumi, Chiaki Kabasawa, Toshiyuki Takahashi, Shinichiro Uchiyama, Kazuo Fujihara, Yuko Shimizu, Norihiro Suzuki, Kimiaki Utsugisawa, Shigeaki Suzuki, Yuriko Nagane, Ryotaro Ikeguchi, Satoru Shimizu, Shiori Hashimoto, and Yasushi Suzuki

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, Treg cell, Asian People, Internal medicine, Myasthenia Gravis, Humans, Medicine, Spectrum disorder, Autoantibodies, Retrospective Studies, Aquaporin 4, Neuromyelitis optica, business.industry, Incidence (epidemiology), Neuromyelitis Optica, General Medicine, Thymectomy, medicine.disease, Myasthenia gravis, Acetylcholine receptor antibody, Aquaporin-4 antibody, Immunology, Female, Surgery, Neurology (clinical), business
Abstract

Background The incidence of concurrent myasthenia gravis (MG) and neuromyelitis optica spectrum disorder (NMOSD) is higher than what chance predicts, yet it remains unclear why MG and NMOSD appear concurrently. Objective The purpose of the present study was to examine the clinical features of the concurrence of these diseases. Methods Clinical details were analyzed retrospectively. Results Three (0.5%) out of 631 MG patients had confirmed ( n =2) or suspected ( n =1) NMOSD. Two of these patients were women. All showed early-onset MG (EOMG) that preceded NMOSD and were positive for acetylcholine receptor antibody (AChR-Ab). Two patients were tested for aquaporin 4 antibody (AQP4-Ab) and were positive. Two patients were treated with a thymectomy that preceded NMOSD. Two patients had decreased frequency of regulatory T (Treg) cells. We identified in the literature 46 patients with both MG and NMOSD. Our results of female predominance, EOMG, MG preceding NMOSD, and positive AChR-Ab are consistent with previous descriptions. Conclusions This is the first report to examine the frequency of NMOSD in Japanese patients with MG. The reduction and/or dysfunction of Treg cells may be one cause of NMOSD development in MG.

Published
2014
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20. Clinical features and treatment status of adult myasthenia gravis in Japan

Author

Shingo Konno, Kimiaki Utsugisawa, Masayuki Masuda, Shigeaki Suzuki, Masakatsu Motomura, Jun Ichi Kira, Tomihiro Imai, Hiroyuki Murai, and Yuriko Nagane

Subjects
medicine.medical_specialty, medicine.medical_treatment, Immunology, Neuroscience (miscellaneous), Gastroenterology, corticosteroids, Treatment status, Immunology and Microbiology (miscellaneous), Internal medicine, medicine, In patient, myasthenia gravis, Adult patients, treatment, business.industry, Autoantibody, medicine.disease, Bulbar symptoms, Myasthenia gravis, Surgery, Thymectomy, classification, Prednisolone, Neurology (clinical), immunotherapy, business, medicine.drug
Abstract

Objective Myasthenia gravis (MG) is classified as early-onset MG (EOMG; age at onset ?49 years), late-onset MG (LOMG; age at onset ?50 years) or thymoma-associated MG (TAMG) (E-L-T classification). To clarify the characteristics of each group in the E-L-T classification in Japan, we carried out multicenter analyses of MG. Methods A total of 640 adult patients from 11 MG centers participated in the study. Age at onset, sex, clinical symptoms, frequency of crisis, thymic pathology, positivity of autoantibodies against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK), selected treatment, Cushingoid appearance and post-intervention status were evaluated in each group. Results EOMG, LOMG and TAMG accounted for 44%, 33%, and 23% of the patients, respectively. Females predominated in the EOMG group (77%), whereas there was no sex difference in the LOMG group. The frequency of ocular MG was the highest in the LOMG group (EOMG 15%, LOMG 38%, TAMG 12%). Bulbar symptoms and crisis were most frequent in the TAMG group. Anti-AChR antibody was always positive in patients with TAMG (EOMG 70%, LOMG 78%, TAMG 99%), whereas anti-MuSK antibody was never positive in TAMG patients, and more frequently detected in EOMG patients than in LOMG patients. Thymectomy was carried out in 51% of EOMG patients, 26% of LOMG patients and 97% of TAMG patients. Immunotherapy was carried out most aggressively in TAMG patients, and least aggressively in LOMG patients. Minimal manifestations or better with prednisolone ?5 mg were achieved only in one-third of EOMG and TAMG patients. Conclusion Thymoma-associated MG required the most aggressive immunotherapy, followed by early-onset MG., Clinical and Experimental Neuroimmunology, 5(1), pp.84-91; 2014

Published
2014

21. Cardiac involvements in myasthenia gravis associated with anti-Kv1.4 antibodies

Author

Kenichi Kaida, G. Ogawa, Norihiro Suzuki, Yuriko Nagane, Shigeaki Suzuki, Y. Kita, Akiyasu Baba, Jun Tsugawa, Kimiaki Utsugisawa, and Masataka Kuwana

Subjects
Adult, Male, medicine.medical_specialty, Thymoma, Myocarditis, Heart Diseases, Ventricular tachycardia, Gastroenterology, Sick sinus syndrome, Electrocardiography, Young Adult, Antigen, Internal medicine, Myasthenia Gravis, medicine, Humans, Aged, Autoantibodies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Heart, Middle Aged, medicine.disease, Myasthenia gravis, Neurology, Heart failure, Cardiology, Kv1.4 Potassium Channel, Female, Neurology (clinical), business
Abstract

Background and purpose There is no general consensus as to whether autoimmune myasthenia gravis (MG) is associated with heart diseases, despite the fact that myocarditis, a serious cardiac involvement treatable by immunotherapy, is a complication of MG. It has been observed previously that MG patients with clinically suspected myocarditis had anti-Kv1.4 antibodies. The purpose of this study was to disclose the association between anti-Kv1.4 antibodies and cardiac involvements in MG patients. Methods Anti-Kv1.4 antibody was detected by an immunoprecipitation assay using 35S-labeled rhabdomyosarcome cellular extract as the antigen source. Cardiac findings including electrocardiography (ECG) and clinical features of clinically suspected myocarditis in MG patients with anti-Kv1.4 antibodies were investigated. Ultrasound echocardiography (UCG) of ex vivo chick embryos was performed to determine the suppressive effects of sera with or without anti-Kv1.4 antibodies on heart muscle functions. Results Seventy (10.8%) of 650 MG patients had anti-Kv1.4 antibodies and 60% of them had abnormal ECG findings with high frequencies of T-wave abnormality and QT prolongation. Clinically suspected myocarditis was found in eight MG patients with anti-Kv1.4 antibodies but in none of the MG patients without anti-Kv1.4 antibodies. Most patients showed rapid deterioration with lethal arrhythmias such as ventricular tachycardia, sick sinus syndrome, or complete atrial ventricular block and severe heart failure. It was concluded using UCG of ex vivo chick embryos that MG serum with anti-Kv1.4 antibodies suppressed heart muscle functions. Conclusion It has been demonstrated that anti-Kv1.4 antibodies are possible markers for cardiac involvements in MG patients.

Published
2013
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22. Clinical and immunological predictors of prognosis for Japanese patients with thymoma-associated myasthenia gravis

Author

Mitsutomo Kohno, Masataka Kuwana, Tetsuya Nishimoto, Norihiro Suzuki, Yuriko Nagane, Shigeaki Suzuki, and Kimiaki Utsugisawa

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Thymoma, Adolescent, Immunology, Enzyme-Linked Immunosorbent Assay, Autoantigens, Gastroenterology, World health, Young Adult, Asian People, Recurrence, hemic and lymphatic diseases, Internal medicine, Myasthenia Gravis, medicine, Humans, Immunology and Allergy, Stage (cooking), Young adult, Child, neoplasms, Autoantibodies, Adjuvant radiotherapy, biology, business.industry, Thymus Neoplasms, Prognosis, medicine.disease, Myasthenia gravis, Neurology, Child, Preschool, biology.protein, Kv1.4 Potassium Channel, Female, Neurology (clinical), Antibody, business
Abstract

There are no immunological markers to predict the prognosis of thymoma-associated myasthenia gravis (MG). Clinical and immunological factors associated with thymoma recurrence or MG relapse were examined by logistic analyses in 56 Japanese patients with thymoma-associated MG. Patients with anti-Kv1.4 antibodies showed higher frequencies of thymoma recurrence and MG relapse compared to those without. Anti-Kv1.4 antibody, Masaoka stage 4, World Health Organization type B3, and adjuvant radiotherapy were associated with thymoma recurrence. Multivariate analyses showed that anti-Kv1.4 antibody was the only independent factor associated with MG relapse. Anti-Kv1.4 antibody is a useful predictor of the prognosis of thymoma-associated MG.

Published
2013
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23. Response to treatment of myasthenia gravis according to clinical subtype

Author

Shingo Konno, Masayuki Masuda, Tetsuya Akaishi, Masashi Aoki, Emiko Tsuda, Tomihiro Imai, Kimiaki Utsugisawa, Hiroyuki Murai, N. Minami, Hidekazu Suzuki, Yasushi Suzuki, Akiyuki Uzawa, Naoki Kawaguchi, and Yuriko Nagane

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Neurology, Thymoma, Adolescent, Clinical Neurology, Kaplan-Meier Estimate, Severity of Illness Index, Gastroenterology, Young Adult, 03 medical and health sciences, Cluster analysis, 0302 clinical medicine, Japan, Internal medicine, Myasthenia Gravis, Severity of illness, medicine, Humans, Young adult, Child, Aged, Aged, 80 and over, business.industry, Autoantibody, Reproducibility of Results, Thymus Neoplasms, General Medicine, Middle Aged, Hyperplasia, Classification, medicine.disease, Myasthenia gravis, Treatment, Onset age, 030104 developmental biology, Myasthenia, Female, Neurology (clinical), Age of onset, business, 030217 neurology & neurosurgery, Research Article
Abstract

Background We have previously reported using two-step cluster analysis to classify myasthenia gravis (MG) patients into the following five subtypes: ocular MG; thymoma-associated MG; MG with thymic hyperplasia; anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; and AChR-Ab-positive MG without thymic abnormalities. The objectives of the present study were to examine the reproducibility of this five-subtype classification using a new data set of MG patients and to identify additional characteristics of these subtypes, particularly in regard to response to treatment. Methods A total of 923 consecutive MG patients underwent two-step cluster analysis for the classification of subtypes. The variables used for classification were sex, age of onset, disease duration, presence of thymoma or thymic hyperplasia, positivity for AChR-Ab or anti–muscle-specific tyrosine kinase antibody, positivity for other concurrent autoantibodies, and disease condition at worst and current. The period from the start of treatment until the achievement of minimal manifestation status (early-stage response) was determined and then compared between subtypes using Kaplan-Meier analysis and the log-rank test. In addition, between subtypes, the rate of the number of patients who maintained minimal manifestations during the study period/that of patients who only achieved the status once (stability of improved status) was compared. Results As a result of two-step cluster analysis, 923 MG patients were classified into five subtypes as follows: ocular MG (AChR-Ab-positivity, 77%; histogram of onset age, skewed to older age); thymoma-associated MG (100%; normal distribution); MG with thymic hyperplasia (89%; skewed to younger age); AChR-Ab-negative MG (0%; normal distribution); and AChR-Ab-positive MG without thymic abnormalities (100%, skewed to older age). Furthermore, patients classified as ocular MG showed the best early-stage response to treatment and stability of improved status, followed by those classified as thymoma-associated MG and AChR-Ab-positive MG without thymic abnormalities; by contrast, those classified as AChR-Ab-negative MG showed the worst early-stage response to treatment and stability of improved status. Conclusions Differences were seen between the five subtypes in demographic characteristics, clinical severity, and therapeutic response. Our five-subtype classification approach would be beneficial not only to elucidate disease subtypes, but also to plan treatment strategies for individual MG patients.

Published
2016
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24. Early fast-acting treatment strategy against generalized myasthenia gravis

Author

Yuriko Nagane, Hidekazu Suzuki, Tetsuya Akaishi, Kimiaki Utsugisawa, Yasushi Suzuki, Tomihiro Imai, Masashi Aoki, Hiroyuki Murai, Naoki Kawaguchi, Akiyuki Uzawa, Masayuki Masuda, Emiko Tsuda, N. Minami, and Shingo Konno

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Time Factors, Physiology, Prednisolone, Anti-Inflammatory Agents, oral steroids, Statistics, Nonparametric, Kaplan–Meier method, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Treatment targets, 0302 clinical medicine, Japan, Clinical Research, treatment strategies, Physiology (medical), Internal medicine, Myasthenia Gravis, medicine, Humans, treatment target, Dosing, Generalized myasthenia, Aged, Proportional hazards model, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, medicine.disease, Myasthenia gravis, myasthenia, Surgery, 030104 developmental biology, Neurology, Treatment strategy, Female, Neurology (clinical), Immunotherapy, business, 030217 neurology & neurosurgery, Cohort study, medicine.drug
Abstract

Introduction In this study we sought to clarify the effects of early fast-acting treatment (EFT) strategies on the time course for achieving the treatment target in generalized myasthenia gravis (MG). Methods This retrospective study of 923 consecutive MG patients analyzed 688 generalized MG patients who had received immunotherapy during the disease course. The time to first achieve minimal manifestations (MM) or better while receiving prednisolone at ≤5 mg/day for ≥6 months (MM-or-better-5mg) up to 120 months after starting immunotherapy was compared between EFT and non-EFT patients. Results Achievement of MM-or-better-5mg was more frequent and earlier in the EFT group (P = 0.0004, Wilcoxon test; P = 0.0001, log-rank test). Multivariate Cox regression analysis calculated a hazard ratio of 1.98 (P < 0.0001) for utilization of EFT. Dosing regimens of oral steroids in EFT produced no differences in the time course. Conclusions EFT strategies are advantageous for early achievement of MM-or-better-5mg. Muscle Nerve 55: 794–801, 2017

Published
2016

25. International clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent validation of the MG-QOL15r

Author

Ted M, Burns, Reza, Sadjadi, Kimiaki, Utsugisawa, Kelly G, Gwathmey, Amruta, Joshi, Sarah, Jones, Vera, Bril, Carolina, Barnett, Jeffrey T, Guptill, Donald B, Sanders, Lisa, Hobson-Webb, Vern C, Juel, Janice, Massey, Karissa L, Gable, Nicholas J, Silvestri, Gil, Wolfe, Gary, Cutter, Yuriko, Nagane, Hiroyuki, Murai, Masayuki, Masuda, Maria Elena, Farrugia, Caroline, Carmichael, Simone, Birnbaum, Jean-Yves, Hogrel, Shahriar, Nafissi, Farzad, Fatehi, Changyi, Ou, Weibin, Liu, and Mark, Conaway

Subjects
Psychometrics, Myasthenia Gravis, Quality of Life, Humans, Retrospective Studies
Abstract

The MG-QOL15 is a validated, health-related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties.We first performed Rasch analysis on1,300 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG-QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on1,300 MG-QOL15r scales.The MGQOL15r performed slightly better than the MG-QOL15. The 3-response option MG-QOL15r demonstrated better clinimetric properties than the 4- or 5-option scales. Relative distributions of item and person location estimates showed good coverage of disease severity.The MG-QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG-QOL15. Muscle Nerve 54: 1015-1022, 2016.

Published
2016

27. Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis

Author

Mitsuhiro Tsujihata, Yuriko Nagane, Masakatsu Motomura, Toshiro Yoshimura, Ruka Nakata, Kimiaki Utsugisawa, Masahiro Tokuda, Taku Fukuda, Atsushi Kawakami, and Tomoko Masuda

Subjects
monoclonal antibody 35, receptor binding, retrospective study, Receptors, Nicotinic, immunoprecipitation, Severity of Illness Index, antibody detection, Monoclonal, antigen binding, generalized myasthenia gravis, biology, adult, Antibody titer, antibody blood level, article, Antibodies, Monoclonal, thymoma, Middle Aged, unclassified drug, Psychiatry and Mental health, female, priority journal, main immunogenic region autoantibody, disease severity, Biological Markers, Antibody, Thymoma, medicine.drug_class, disease classification, Monoclonal antibody, antibody titer, bulbar paralysis, Antibodies, ocular myasthenia gravis, male, Myasthenia Gravis, medicine, Humans, Animals, controlled study, human, Acetylcholine receptor, Autoantibodies, Retrospective Studies, business.industry, Autoantibody, scoring system, prediction, medicine.disease, major clinical study, Myasthenia gravis, Rats, monoclonal antibody, Rats, Inbred Lew, Immunology, biology.protein, Surgery, Neurology (clinical), nicotinic receptor alpha, business, nicotinic receptor, Biomarkers, autoantibody
Abstract

Objective: We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) a subunit, and investigated its clinical relevance in myasthenia gravis (MG). Methods: In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35. Results: 11 of 23 (47.8%) ocular type and 66 of 72 (91.7%) generalised type MG patients were positive for the presence of MIR Abs, defined as a titre >16.8% (3 SDs above the mean for 70 healthy controls). A significantly higher MIR Ab titre (p, Journal of Neurology, Neurosurgery & Psychiatry, 83(9), pp.935-940; 2012

Published
2012

28. Autoimmunity to endoplasmic reticulum chaperone GRP94 in myasthenia gravis

Author

Yuriko Nagane, Hiroaki Yoshikawa, Kazuo Iwasa, Kimiaki Utsugisawa, Norihiro Suzuki, Shigeaki Suzuki, Takashi Satoh, and Masataka Kuwana

Subjects
Adult, Male, medicine.medical_specialty, Immunoprecipitation, Immunology, Endoplasmic Reticulum, medicine.disease_cause, Autoantigens, Autoimmunity, Pathogenesis, Young Adult, Immune system, Cell Line, Tumor, Internal medicine, Myasthenia Gravis, medicine, Humans, Immunology and Allergy, Aged, Autoantibodies, Retrospective Studies, Membrane Glycoproteins, Chemistry, Endoplasmic reticulum, Autoantibody, Middle Aged, medicine.disease, Myasthenia gravis, Endocrinology, Neurology, Unfolded protein response, Female, Neurology (clinical), Molecular Chaperones
Abstract

Immune responses to ER stress have been closely related to the pathogenesis of autoimmune diseases. Using an immunoprecipitation assay, 24 (7.1%) of 336 MG serum samples immunoprecipitated a 90-kDa protein from the muscle cellular extracts, but none of the disease or healthy control sera. The 90-kDa protein was affinity-purified and found to match to ER chaperon GRP94 by matrix-assisted laser desorption/ionization-time of flight mass spectroscopy analysis. The frequency of associated autoimmune diseases was much higher in the anti-GRP94-positive than the -negative patients (71% versus 11%, p0.001). Autoimmunity to ER chaperone GRP94 is associated with a subset of MG patients who have additional autoimmune diseases.

Published
2011
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29. Topical naphazoline in the treatment of myasthenic blepharoptosis

Author

Norihiro Suzuki, Shigeaki Suzuki, Yuriko Nagane, Shinichiro Uchiyama, Masayuki Masuda, Kimiaki Utsugisawa, Yuko Shimizu, and Hiroya Utsumi

Subjects
Adult, Male, genetic structures, Physiology, medicine.drug_class, Administration, Topical, Ocular myasthenia, Symptomatic treatment, Cellular and Molecular Neuroscience, Physiology (medical), Myasthenia Gravis, Blepharoptosis, Humans, Medicine, Aged, business.industry, Eyewash, Naphazoline, Middle Aged, medicine.disease, eye diseases, Myasthenia gravis, Clinical trial, Pharmaceutical Solutions, Treatment Outcome, Anesthesia, Corticosteroid, Female, Neurology (clinical), Open label, business, medicine.drug
Abstract

Introduction. When treating ocular myasthenia gravis (MG), the risk/benefit profile of corticosteroids is unclear, and acetylcholinesterase inhibitors are not very effective. We examined the efficacy of topical naphazoline in the treatment of myasthenic blepharoptosis. Methods. Sixty MG patients with blepharoptosis (32 with ocular symptoms only and 28 with mild generalized symptoms) were enrolled in a multicenter open trial of topical naphazoline. The effects were reported by patients via a questionnaire and were also confirmed for each patient at the clinic. Results. Among 70 eyes of 60 patients, 20 eyes (28.6%) of 17 patients (28.3%) exhibited a marked response (full eye opening), and 24 eyes (34.3%) of 20 patients (33.3%) showed a good response (adequate but incomplete eye opening). Topical naphazoline was evaluated as useful in the treatment of myasthenic blepharoptosis by >70% of the patients. Conclusions. Topical naphazoline was found to be an effective supplementary symptomatic treatment for myasthenic blepharoptosis. Muscle Nerve 44: 41–44, 2011.

Published
2011
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30. Three Types of Striational Antibodies in Myasthenia Gravis

Author

Yuriko Nagane, Kimiaki Utsugisawa, Norihiro Suzuki, and Shigeaki Suzuki

Subjects
lcsh:Immunologic diseases. Allergy, Pathology, medicine.medical_specialty, Thymoma, biology, business.industry, Ryanodine receptor, Immunology, Autoantibody, Review Article, medicine.disease, Neuromuscular junction, Myasthenia gravis, Epitope, medicine.anatomical_structure, Immunology and Microbiology (miscellaneous), biology.protein, Immunology and Allergy, Medicine, Antibody, lcsh:RC581-607, business, Acetylcholine receptor
Abstract

Myasthenia gravis (MG) is caused by antibodies that react mainly with the acetylcholine receptor on the postsynaptic site of the neuromuscular junction. A wide range of clinical presentations and associated features allow MG to be classified into subtypes based onautoantibodystatus. Striational antibodies, which react with epitopes on the muscle proteins titin, ryanodine receptor (RyR), and Kv1.4, are frequently found in MG patients with late-onset and thymoma. Antititin and anti-RyR antibodies are determined by enzyme-linked immunosorbent assay or immunoblot. More recently, a method for the detection of anti-Kv1.4 autoantibodies has become available, involving 12–15% of all MG patients. The presence of striational antibodies is associated with more severe disease in all MG subgroups. Anti-Kv1.4 antibody is a useful marker for the potential development of lethal autoimmune myocarditis and response to calcineurin inhibitors. Detection of striational antibodies provides more specific and useful clinical information in MG patients.

Published
2011
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31. Headache Associated with Myasthenia Gravis: The Impact of Mild Ocular Symptoms

Author

Mamoru Shibata, Yoshinori Nishimoto, Yuriko Nagane, Toshihiko Shimizu, Norihiro Suzuki, Shigeaki Suzuki, and Kimiaki Utsugisawa

Subjects
lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Article Subject, business.industry, Immunology, medicine.disease, Myasthenia gravis, Immunology and Microbiology (miscellaneous), Migraine, Internal medicine, Clinical Study, medicine, Physical therapy, Immunology and Allergy, Outpatient clinic, lcsh:RC581-607, business
Abstract

Myasthenia gravis (MG) patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG). We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6%) patients and 9 (4.9%) complained of migraine. Twenty-five (13.6%) complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients.

Published
2011
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32. Is Surgical Intervention Safe and Effective in the Treatment of Myasthenic Blepharoptosis? A Multicenter Survey in Japan

Author

Norihiro Suzuki, Shigeaki Suzuki, Tomohisa Nagasao, Emiko Tsuda, Kimiaki Utsugisawa, Hisao Ogata, Yusuke Shimizu, Tomihiro Imai, Kazuo Kishi, Hiroyuki Murai, Masaki Yazawa, and Yuriko Nagane

Subjects
Adult, Male, medicine.medical_specialty, Ocular myasthenia, Neuromuscular transmission, MEDLINE, Young Adult, Patient satisfaction, Japan, Surveys and Questionnaires, Intervention (counseling), Myasthenia Gravis, Blepharoptosis, Humans, Medicine, Young adult, Aged, business.industry, General surgery, Middle Aged, medicine.disease, Myasthenia gravis, Surgery, Treatment Outcome, medicine.anatomical_structure, Neurology, Patient Satisfaction, Female, Neurology (clinical), Eyelid, business
Abstract

neurological centers constituting the Japan MG Registry Study Group. All of the patients were interviewed about the clinical features of their MG and whether they had undergone blepharoptosis surgery. A total of 19 patients (2.8%; 7 men, 12 women; mean age: 65.7 years) had undergone blepharoptosis surgery, and were further evaluated by using a questionnaire. Questions regarding the timing of the surgery (relative to MG onset), the ease of eyelid opening [over both the short term ( ≤ 1 year) and long term (>1 year), postoperatively], aesthetic outcome (scarring), overall satisfaction with the surgery, and any noted complications. Three-point Likert scales were used to assess the ease of eyelid opening (much easier, easier, worse), scarring (very minimal, minimal, visible), and overall satisfaction with the surgery (very satisfied, satisfied, dissatisfied). To evaluate scarring, the patients answered the questionnaires with their attending neurologists in the out-patient clinics. The actual surgeons were not present to help in obtaining unbiased opinions from the patients. All clinical information was collected after the patients had provided written Dear Sir, Myasthenia gravis (MG) is an antibodymediated, neuromuscular transmission disorder. Its clinical manifestations range from ocular myasthenia, which can be visually disabling, to myasthenic crisis, with patients experiencing life-threatening respiratory insufficiencies [1] . Several effective medical treatments are available for the ocular symptoms of MG [2–6] ; however, physicians often struggle to treat patients with longstanding blepharoptosis [7–9] . Moreover, although blepharoptosis surgery is occasionally applied in such cases [10, 11] , the indications and clinical effectiveness of blepharoptosis surgery for MG patients remains unclear. In the present study, we retrospectively investigated the clinical features of blepharoptosis surgery by interviewing 19 Japanese patients with MG.

Published
2014
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33. Early Aggressive Treatment Strategy against Myasthenia Gravis

Author

Yuriko Nagane, Norihiro Suzuki, Shigeaki Suzuki, and Kimiaki Utsugisawa

Subjects
Pediatrics, medicine.medical_specialty, Prednisolone, medicine.medical_treatment, Treatment outcome, MEDLINE, Methylprednisolone, Myasthenia Gravis, medicine, Humans, Retrospective Studies, Dose-Response Relationship, Drug, business.industry, Retrospective cohort study, Plasmapheresis, medicine.disease, Myasthenia gravis, Surgery, Treatment Outcome, Neurology, Treatment strategy, Neurology (clinical), business, Immunosuppressive Agents, medicine.drug
Abstract

Background/Aims: In treating myasthenia gravis (MG), our aims were to achieve early minimal manifestations (MM) by performing early aggressive therapy (EAT) using plasmapheresis and high-dose intravenous methylprednisolone, and then to maintain the status with low-dose oral corticosteroids (EAT strategy). We examined the merits of the EAT strategy. Methods: We retrospectively analyzed long-term effects of the EAT strategy (duration of therapy: 4.1 years) for 49 de novo MG patients and compared the effects to those of high-dose oral prednisolone therapy for 22 patients. Results: The EAT group achieved marked early improve- ment with much lower doses of oral prednisolone compared to the high-dose prednisolone group. The patients who achieved MM with prednisolone ≤5 mg/day were more frequent in the EAT group at both 1 year (57.1 vs. 4.5%) and final observation (77.6 vs. 27.3%). Both new-onset diabetes and patients who had complained of moon face were less frequent in the EAT group. However, in the EAT group, due to a temporary inability to maintain MM, additional short-term hospitalizations to return to MM by EAT were required. Conclusions: The EAT strategy has advantages of early improvement with less frequent steroid-related complications. The labor and cost required are evident disadvantages.

Published
2010
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34. Two-Year Treatment with Cyclosporine Microemulsion for Responder Myasthenia Gravis Patients

Author

Yuriko Nagane, Kimiaki Utsugisawa, Norihiro Suzuki, and Shigeaki Suzuki

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, MEDLINE, Severity of Illness Index, Statistics, Nonparametric, Internal medicine, Myasthenia Gravis, Severity of illness, medicine, Humans, Longitudinal Studies, Aged, Chi-Square Distribution, integumentary system, business.industry, Cyclosporine microemulsion, Middle Aged, medicine.disease, Myasthenia gravis, Clinical trial, Neurology, Anesthesia, Cyclosporine, Emulsions, Female, Neurology (clinical), business, Chi-squared distribution, Immunosuppressive Agents
Abstract

Background: Cyclosporine (CsA) microemulsion pre-concentrate (MEPC) is a potential steroid-sparing agent for myasthenia gravis (MG) patients; however, there is a paucity of information on the long-term use of CsA MEPC in these patients. Objectives: We examined the efficacy and safety of CsA MEPC therapy administered to MG patients in a 2-year prospective open trial. Methods: From Hanamaki General Hospital and Keio University Hospital, 28 patients provided informed consent. They were enrolled in a prospective open study of CsA MEPC for the initial 6-month observation period; after this 9 were defined as poor responders and excluded from the long-term analysis. Results: The proportion of patients with minimal manifestations or pharmacologic remission status increased significantly. Among 18 patients taking oral prednisolone, 16 (88.9%) achieved a ≧50% reduction in prednisolone dose. Time to attain the minimal quantitative MG (QMG) score (4.2 ± 2.6) was 4.2 ± 4.2 months. Time to attain the minimal dose of prednisolone (2.9 ± 3.1 mg/day) was 9.3 ± 6.9 months. The dose of CsA MEPC was reduced to 2.6 mg/kg/day 2 years after starting the drug. Both total and ocular QMG scores were significantly decreased at 6 months and were generally maintained thereafter. The dose of prednisolone was significantly reduced at 1 year, and further reduced at 2 years. BMI decreased significantly, and 9 of 12 (75%) patients complaining of moon face reported that this had resolved on exit. All patients tolerated CsA MEPC without significant side effects. Conclusion: CsA MEPC therapy in responder MG patients suppressed disease severity, reduced steroid requirements, and alleviated steroid-related side effects. These findings should be confirmed by prospective controlled double-blind trials.

Published
2010
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35. Factors associated with response to calcineurin inhibitors in myasthenia gravis

Author

Yuriko Nagane, Kimiaki Utsugisawa, Norihiro Suzuki, and Shigeaki Suzuki

Subjects
medicine.medical_specialty, Thymoma, Physiology, business.industry, Autoantibody, Cancer, Odds ratio, medicine.disease, Gastroenterology, Tacrolimus, Myasthenia gravis, Calcineurin, Cellular and Molecular Neuroscience, Endocrinology, Physiology (medical), Internal medicine, Prednisolone, medicine, Neurology (clinical), business, medicine.drug
Abstract

The objective was to assess which clinical factors of patients with myasthenia gravis (MG) are associated with responsiveness to calcineurin inhibitors (CNIs, cyclosporine and tacrolimus). We retrospectively analyzed the 6-month effects of CNIs in 62 MG patients. We excluded the influence of other immune treatments and determined factors associated with response to CNIs. The frequency of patients who achieved neither a ≥3-point reduction in quantitative MG score nor a ≥25% reduction in daily dose of prednisolone (poor responders) reached 35.5% (22/62) and 64.5% (40/62), respectively, compared with patients who achieved at least one of these improvements (responders). Neither dose nor blood concentration of CNIs differed between groups. Multivariate logistic regression analysis revealed time since onset of disease [odds ratio (OR) = 0.85, P = 0.005] and presence of thymoma (OR = 5.56, P = 0.05) as clinical factors that predict response to CNIs. As for MG-related autoantibody status, an autoantibody against a voltage-gated potassium channel, Kv1.4, was associated with response (OR = 9.01, P = 0.04) and showed a correlation with the presence of thymoma (P < 0.01). In MG, the early stages of disease and thymoma-associated MG are responsive to treatment with CNIs. Muscle Nerve, 2010

Published
2009
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37. Association between Glucocorticoid-Induced Osteoporosis and Myasthenia Gravis: A Cross-Sectional Study

Author

Emiko Tsuda, Yuriko Nagane, Shingo Konno, Hiroyuki Murai, Tomihiro Imai, Kimiaki Utsugisawa, Toshiki Fujioka, Norihiro Suzuki, Shigeaki Suzuki, and Masayuki Masuda

Subjects
Adult, Male, medicine.medical_specialty, Bone density, Osteoporosis, lcsh:Medicine, Fractures, Bone, Quality of life, Bone Density, Internal medicine, Myasthenia Gravis, medicine, Humans, lcsh:Science, Glucocorticoids, Aged, Bone mineral, Multidisciplinary, business.industry, lcsh:R, Bone fracture, Middle Aged, medicine.disease, Myasthenia gravis, Surgery, Prednisolone, Quality of Life, lcsh:Q, Female, business, Glucocorticoid, medicine.drug, Research Article
Abstract

Purpose To investigate the association between glucocorticoid-induced osteoporosis and myasthenia gravis (MG) using a cross-sectional survey in Japan. Methods We studied 363 patients with MG (female 68%; mean age, 57 ± 16 years) who were followed at six Japanese centers between April and July 2012. We evaluated the clinical information of MG and fractures, bone markers, and radiological assessment. Quality of life was measured using an MG-specific battery, MG-QOL15. Results Glucocorticoids were administered in 283 (78%) of 363 MG patients. Eighteen (6%) of 283 MG patients treated with prednisolone had a history of osteoporotic fractures. The duration of glucocorticoid therapy, but not the dose of prednisolone, was associated with the osteoporotic fractures in MG patients. Bone mineral density was significantly decreased in the MG patients with fractures. The multivariate analyses showed that the total quantitative MG score was the only independent factor associated with osteoporotic fractures (OR = 1.30, 95% CI 1.02–1.67, p = 0.03). MG patients who had experienced fractures reported more severe difficulties in activities of daily living. Conclusion Glucocorticoid-induced osteoporosis aggravates quality of life in patients with MG.

Published
2015

38. Interleukin-2 Production by Peripheral Blood Mononuclear Cells from Patients with Myasthenia gravis

Author

Daiji Obara, Hideo Tohgi, Kimiaki Utsugisawa, Yuriko Nagane, Ryushi Kondoh, and Hisashi Yonezawa

Subjects
Adult, Male, Interleukin 2, medicine.medical_specialty, medicine.medical_treatment, chemical and pharmacologic phenomena, Peripheral blood mononuclear cell, Monocytes, Pathogenesis, Reference Values, Internal medicine, Myasthenia Gravis, medicine, Humans, Aged, Aged, 80 and over, biology, business.industry, fungi, Middle Aged, Hyperplasia, medicine.disease, Myasthenia gravis, Thymectomy, Endocrinology, Cytokine, Neurology, biology.protein, Interleukin-2, Female, Neurology (clinical), Antibody, business, medicine.drug
Abstract

We examined interleukin-2 (IL-2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMs) from 75 untreated myasthenia gravis (MG) patients and 48 control patients. Patients with MG consisted of those with elevated PBM IL-2 production (>1,250 pg/ml; mean + 2SD of the controls) (n = 29, 39%) and those with normal PBM IL-2 production (

Published
2003
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39. Taste disorders in myasthenia gravis: a multicenter cooperative study

Author

Chiaki Kabasawa, Yuriko Nagane, Y. Shimizu, Shinichiro Uchiyama, Hiroya Utsumi, Y. Suzuki, Kazuo Fujihara, Masayuki Masuda, Norihiro Suzuki, Shigeaki Suzuki, and Kimiaki Utsugisawa

Subjects
education.field_of_study, medicine.medical_specialty, Chemotherapy, Thymoma, business.industry, medicine.medical_treatment, Population, Clinical course, Sweet taste, medicine.disease, Gastroenterology, Myasthenia gravis, Surgery, Neurology, Multicenter study, Taste disorder, Internal medicine, medicine, Neurology (clinical), education, business
Abstract

Background and purpose: The purpose of the present study was to investigate the prevalence and clinical characteristics of taste disorders in patients with myasthenia gravis (MG). Methods: We studied 371 Japanese patients with MG (127 men and 244 women; mean age, 56.6 ± 16.9 years) consecutively evaluated between May and September 2010 in six neurological centers comprising the East Japan MG Study Group. Ninety-three patients (25%) had thymoma. We interviewed all patients to determine whether they had taste disorders during the clinical course of MG and then further evaluated the patients with MG, who reported having taste disorders, using a questionnaire. Results: Taste disorders were observed in 16 (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of patients with MG excluding other factors were associated with MG itself. All patients had thymoma with seropositivity for anti-acetylcholine receptor antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage IVa required radiation therapy or chemotherapy. Five patients noticed taste disorders 2–3 months before the onset of MG. Sweet taste loss was more common than salty, bitter, and sour taste loss. Conclusions: This was the first systematic survey of taste disorders in patients with MG by a multicenter study. Taste disorders were more common in the present sample of patients with MG than in the general population.

Published
2012
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40. Sex differences in prognosis and quality of life in myasthenia gravis

Author

Tetsuya Akaishi, Hiroyuki Murai, Hidekazu Suzuki, Tomihiro Imai, Kimiaki Utsugisawa, Yasushi Suzuki, Shingo Konno, Naoki Kawaguchi, Tetsuya Kanai, Yuriko Nagane, E. Tstuda, Masayuki Masuda, Toshiki Fujioka, N. Minami, and Akiyuki Uzawa

Subjects
Pediatrics, medicine.medical_specialty, Quality of life (healthcare), Neurology, business.industry, Medicine, Neurology (clinical), business, medicine.disease, Myasthenia gravis
Published
2017
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41. Social disadvantages associated with myasthenia gravis and its treatment: A multicenter cross-sectional study

Author

N. Minami, D. Yamamoto, Tetsuya Kanai, Yuriko Nagane, Naoki Kawaguchi, Tomihiro Imai, Shingo Konno, Emiko Tsuda, Kimiaki Utsugisawa, Masayuki Masuda, Hidekazu Suzuki, Yasushi Suzuki, Akiyuki Uzawa, Masashi Aoki, and Hiroyuki Murai

Subjects
Pediatrics, medicine.medical_specialty, Neurology, Cross-sectional study, business.industry, medicine, Neurology (clinical), medicine.disease, business, Myasthenia gravis
Published
2017
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42. Oral corticosteroid therapy and present disease status in myasthenia gravis

Author

Tomihiro, Imai, Shigeaki, Suzuki, Emiko, Tsuda, Yuriko, Nagane, Hiroyuki, Murai, Masayuki, Masuda, Shingo, Konno, Yasushi, Suzuki, Shunya, Nakane, Kazuo, Fujihara, Norihiro, Suzuki, and Kimiaki, Utsugisawa

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Dose-Response Relationship, Drug, Plasma Exchange, Prednisolone, Administration, Oral, Immunoglobulins, Intravenous, Middle Aged, Combined Modality Therapy, Severity of Illness Index, Young Adult, Cross-Sectional Studies, Treatment Outcome, Japan, Adrenal Cortex Hormones, Myasthenia Gravis, Humans, Regression Analysis, Female, Longitudinal Studies, Aged
Abstract

The aim of this study was to elucidate the effectiveness of oral prednisolone (PSL) according to dosing regimen in 472 patients with myasthenia gravis (MG).We compared the clinical characteristics and PSL treatment between 226 patients who achieved minimal manifestations (MM) or better and 246 patients who remained improved (I) or worsened, according to the MG Foundation of America postintervention status.Achievement of MM or better at peak PSL dose (odds ratio 12.25, P 0.0001) and combined use of plasma exchange/plasmapheresis (PE/PP) and/or intravenous immunoglobulin (IVIg) (odds ratio 1.92, P = 0.04) were associated positively, and total PSL dose during the past year (odds ratio 0.17, P = 0.03) was associated negatively with present MM or better status.Higher PSL dose and longer PSL treatment do not ensure better outcome. In the absence of a good response, the PSL dose should be decreased by combining with modalities such as PE/PP or IVIg.

Published
2014

43. Insights into the classification of myasthenia gravis

Author

Yuriko Nagane, Yasushi Suzuki, Kazuo Fujihara, Takuhiro Yamaguchi, Tetsuya Akaishi, Shigeaki Suzuki, Kimiaki Utsugisawa, Hiroyuki Murai, Masashi Aoki, Tomihiro Imai, and Masakatsu Motomura

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Thymoma, medicine.medical_treatment, Immunology, lcsh:Medicine, Young Adult, Myasthenia Gravis, medicine, Medicine and Health Sciences, Cluster Analysis, Humans, Age of Onset, lcsh:Science, Aged, Multidisciplinary, Models, Statistical, business.industry, lcsh:R, Biology and Life Sciences, Thymus Neoplasms, Neuromuscular Diseases, Middle Aged, medicine.disease, Myasthenia gravis, Thymectomy, Neurology, Age distribution, lcsh:Q, Female, Clinical Immunology, business, Research Article
Abstract

Background and Purpose Myasthenia gravis (MG) is often categorized into thymoma-associated MG, early-onset MG with onset age

Published
2014

44. NKT-associated markers and perforin in hyperplastic thymuses from patients with Myasthenia gravis

Author

Hideo Tohgi, Daiji Obara, Yuriko Nagane, and Kimiaki Utsugisawa

Subjects
Adult, Male, Pore Forming Cytotoxic Proteins, Pathology, medicine.medical_specialty, Adolescent, Physiology, Receptors, Antigen, T-Cell, alpha-beta, medicine.medical_treatment, Connective tissue, chemical and pharmacologic phenomena, Thymus Gland, Biology, Natural killer cell, Cellular and Molecular Neuroscience, Immune system, Physiology (medical), Myasthenia Gravis, Parenchyma, medicine, Humans, Membrane Glycoproteins, Perforin, hemic and immune systems, Natural killer T cell, medicine.disease, Immunohistochemistry, CD56 Antigen, Myasthenia gravis, Killer Cells, Natural, Thymectomy, Hyaluronan Receptors, medicine.anatomical_structure, Female, Thymus Hyperplasia, Neurology (clinical), Thymus hyperplasia, Biomarkers
Abstract

Immunohistochemical expression of natural killer T (NKT) cell-associated markers (Valpha24 and CD56) and perforin in relation to CD44-highly positive (CD44(high)) cells was studied in hyperplastic thymuses from patients with myasthenia gravis (MG) whose symptoms dramatically improved after thymectomy and compared with non-MG control thymuses. In the control thymuses, Valpha24-positive (Valpha24(+)) and CD56-positive (CD56(+)) cells were sparsely distributed in the medullary area only. In contrast, in hyperplastic MG thymus, Valpha24(+) and CD56(+) cells were more frequent in connective tissue, appeared to have penetrated the thymic parenchyma, and most coexpressed CD44(high). Perforin-positive cells were not present in the control thymus, but were in the connective tissue and perilobular cortical areas in the hyperplastic MG thymus. Most of these perforin-positive cells were CD44(high) and were located near blood vessels. They appeared to have migrated directly from the vascular system and penetrated the thymic parenchyma. Some perforin-positive cells coexpressed Valpha24, CD56, or both. These findings suggest that in this particular type of MG thymus, NKT-like cells may have increased via a CD44- and perforin-mediated mechanism, leading to an imbalance in the immune system that favored an antibody-mediated autoimmunity against the acetylcholine receptor.

Published
2001
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45. Perivascular infiltrate of memory lymphocytes and mature dendritic cells in MG thymomas

Author

Y Sato, Kimiaki Utsugisawa, Y Terayama, H Akutsu, and Yuriko Nagane

Subjects
Male, Pathology, medicine.medical_specialty, Thymoma, T-Lymphocytes, Lymphocyte, medicine.medical_treatment, Autoimmunity, chemical and pharmacologic phenomena, Thymus Gland, Lymphocyte Activation, medicine.disease_cause, Myasthenia Gravis, medicine, Humans, Receptors, Cholinergic, In patient, Lymphocytes, Receptor, Aged, business.industry, Dendritic Cells, Dendritic cell, Middle Aged, Thymectomy, medicine.disease, Myasthenia gravis, medicine.anatomical_structure, Immunology, Blood Vessels, Female, Neurology (clinical), business
Abstract

In thymomas associated with myasthenia gravis (MG), the authors found that perivascular infiltrates of memory lymphocytes and mature dendritic cells (DCs) were more frequent in patients with early improvement after thymectomy than in patients without response to thymectomy. Although these findings may be limited to particular types of thymoma, thymectomy may interrupt the recruitment of mature DCs in thymus and export of activated T cells to extra-thymic tissues, thereby improving the disease.

Published
2005
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46. [Clinical factors affecting quality of life and treatment targets in patients with myasthenia gravis]

Author

Yuriko Nagane

Subjects
Adult, Male, medicine.medical_specialty, Activities of daily living, Cross-sectional study, Prednisolone, Cushingoid, Cohort Studies, Quality of life, Internal medicine, Myasthenia Gravis, Medicine, Humans, Multicenter Studies as Topic, Cushing Syndrome, Aged, business.industry, Depression, Remission Induction, Middle Aged, medicine.disease, Myasthenia gravis, Cross-Sectional Studies, Total dose, Quality of Life, Female, Neurology (clinical), business, Cohort study, medicine.drug, Follow-Up Studies
Abstract

Presently, myasthenia gravis (MG) is seldom lethal. However, full remission without immune treatment is not common, and many patients still find it difficult to maintain daily activities. To both determine factors affecting health-related quality of life (QOL) and propose an appropriate treatment target for patients with MG, we evaluated 640 consecutive patients with MG seen at 11 neurological centers. Two-year follow-up data were obtained for 282 patients. Correlations between detailed clinical facotrs and the Japanese version of the 15-item MG-specific QOL scale were analyzed.In the cross-sectional analysis of 640 MG patients, multivariate regression revealed that disease severity as evaluated by MG Composite (p < 0.0001), but not quantitative MG score, total dose of oral prednisolone (p = 0.002), but not current dose, and Cushingoid appearance index (p = 0.0004) showed significant negative effects on QOL. Achieving status of Minimal Manifestations or better with prednisolone ≤ 5 mg/day was found to exert a major positive impact on QOL in both the cross-sectional and 2-year follow-up patient samples and can be recommended as a treatment target.

Published
2013

47. Health-related quality-of-life and treatment targets in myasthenia gravis

Author

Kimiaki, Utsugisawa, Shigeaki, Suzuki, Yuriko, Nagane, Masayuki, Masuda, Hiroyuki, Murai, Tomihiro, Imai, Emiko, Tsuda, Shingo, Konno, Shunya, Nakane, Yasushi, Suzuki, Kazuo, Fujihara, and Norihiro, Suzuki

Subjects
Adult, Male, Health Status, Statistics as Topic, Middle Aged, Severity of Illness Index, Self Concept, Cross-Sectional Studies, Japan, Myasthenia Gravis, Quality of Life, Humans, Female, Longitudinal Studies, Aged
Abstract

The aim of this study was to determine factors affecting health-related quality of life (HRQOL) and to propose appropriate treatment targets for patients with myasthenia gravis (MG).We evaluated 640 consecutive patients with MG seen at 11 neurological centers. Two-year follow-up data were obtained for 282 patients. Correlations between detailed clinical factors and the Japanese version of the 15-item MG-specific QOL scale score were analyzed.In a cross-sectional analysis of 640 MG patients, multivariate regression revealed that disease severity, as evaluated by the MG Composite (P0.0001), total dose of oral prednisolone during the last year (P=0.002), and Cushingoid appearance index (P=0.0004), showed significant negative effects on HRQOL, but the quantitative MG score and current prednisolone dose did not.Achieving minimal manifestations (MM) status or better with prednisolone ≤ 5 mg/day was found to exert a major positive impact on HRQOL in both the cross-sectional and 2-year follow-up patient samples and can be recommended as a treatment target.

Published
2013

48. [Therapeutic strategies against myasthenia gravis]

Author

Kimiaki, Utsugisawa and Yuriko, Nagane

Subjects
Adrenal Cortex Hormones, Prednisolone, Calcineurin Inhibitors, Myasthenia Gravis, Quality of Life, Humans, Immunosuppressive Agents
Abstract

Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients takingor = 5 mg prednisolne/day is identically good as that seen in CSR and is a target of treatment. In order to achieve early MM or better status with prednisolneor = 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors.

Published
2013

49. Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan.

Author

Tomihiro Imai, Kimiaki Utsugisawa, Hiroyuki Murai, Emiko Tsuda, Yuriko Nagane, Yasushi Suzuki, Naoya Minami, Akiyuki Uzawa, Naoki Kawaguchi, Masayuki Masuda, Shingo Konno, Hidekazu Suzuki, Tetsuya Akaishi, Masashi Aoki, Imai, Tomihiro, Utsugisawa, Kimiaki, Murai, Hiroyuki, Tsuda, Emiko, Nagane, Yuriko, and Suzuki, Yasushi

Subjects
MYASTHENIA gravis, PREDNISOLONE, CORTICOSTEROIDS, IMMUNOSUPPRESSION, THERAPEUTICS, PROGNOSIS
Abstract

Objective: We examined the correlation between the dosing regimen of oral prednisolone (PSL) and the achievement of minimal manifestation status or better on PSL ≤5 mg/day lasting >6 months (the treatment target) in patients with generalised myasthenia gravis (MG).Methods: We classified 590 patients with generalised MG into high-dose (n=237), intermediate-dose (n=187) and low-dose (n=166) groups based on the oral PSL dosing regimen, and compared the clinical characteristics, previous treatments other than PSL and prognosis between three groups. The effect of oral PSL dosing regimen on the achievement of the treatment target was followed for 3 years of treatment.Results: To achieve the treatment target, ORs for low-dose versus high-dose regimen were 10.4 (P<0.0001) after 1 year of treatment, 2.75 (P=0.007) after 2 years and 1.86 (P=0.15) after 3 years; and those for low-dose versus intermediate-dose regimen were 13.4 (P<0.0001) after 1 year, 3.99 (P=0.0003) after 2 years and 4.92 (P=0.0004) after 3 years. Early combined use of fast-acting treatment (OR: 2.19 after 2 years, P=0.02; OR: 2.11 after 3 years, P=0.04) or calcineurin inhibitors (OR: 2.09 after 2 years, P=0.03; OR: 2.36 after 3 years, P=0.02) was associated positively with achievement of treatment target.Conclusion: A low-dose PSL regimen with early combination of other treatment options may ensure earlier achievement of the treatment target in generalised MG. [ABSTRACT FROM AUTHOR]

Published
2018
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50. [The MG-QOL15 Japanese version: validation and associations with clinical factors]

Author

Chiaki Kabasawa, Yasushi Suzuki, Shinichiro Uchiyama, Kimiaki Utsugisawa, Norihiro Suzuki, Shigeaki Suzuki, Yuriko Nagane, Suguru Ito, Hiroya Utsumi, Masayuki Masuda, Kazuo Fujihara, and Yuko Shimizu

Subjects
medicine.medical_specialty, Multivariate analysis, business.industry, Cross-sectional study, Concurrent validity, Mg composite, humanities, Mg qol15, Disease severity, Quality of life, Internal medicine, Surveys and Questionnaires, Myasthenia Gravis, medicine, Quality of Life, Humans, Neurology (clinical), business, Depression (differential diagnoses)
Abstract

We produced a Japanese translation of the 15-item myasthenia gravis (MG)-specific quality of life (QOL) scale (MG-QOL15), assessed its reliability and validity, and examined clinical factors affecting the self-perceived QOL in MG. Consecutive 327 patients with MG seen at six neurological centers were evaluated. All patients completed an MG-QOL15 Japanese version (MG-QOL15-J), the Beck Depression Inventory-Second Edition (BDI-II), and a generic health-related QOL questionnaire, the SF-36. Disease severity was determined according to the MG Foundation of America (MGFA) quantitative MG score and the MG composite. The MG-QOL15-J exhibited adequate internal reliability, test-retest repeatability, and concurrent validity with SF-36, disease severity, and known-patient groups categorized by MGFA postintervention status. Multivariate analysis revealed severity, dose of oral corticosteroids, and BDI-II as independent factors negatively affecting QOL. The MG-QOL15-J is anticipated to be a valuable clinical measure of QOL in Japanese patients with MG.

Published
2012

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