Author: "Yuriko Nagane" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Yuriko Nagane"' showing total 119 results

Start Over Author "Yuriko Nagane"

119 results on '"Yuriko Nagane"'

1. Real‐world experience with eculizumab and switching to ravulizumab for generalized myasthenia gravis

Author: Daiki Tokuyasu, Shigeaki Suzuki, Akiyuki Uzawa, Yuriko Nagane, Masayuki Masuda, Shingo Konno, Tomoya Kubota, Makoto Samukawa, Takamichi Sugimoto, Kei Ishizuchi, Munenori Oyama, Manato Yasuda, Hiroyuki Akamine, Yosuke Onishi, Yasushi Suzuki, Naoki Kawaguchi, Naoya Minami, Takashi Kimura, Masanori P. Takahashi, Hiroyuki Murai, and Kimiaki Utsugisawa
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Objective Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti‐acetylcholine receptor‐positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real‐world experience. Methods Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG‐ADL. We performed a questionnaire of preference between eculizumab and ravulizumab. Results Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG‐ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab. Interpretation Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings.
Published: 2024
Full Text: View/download PDF

2. Taste disorders and alopecia in myasthenia gravis

Author: Akiyuki Uzawa, Shigeaki Suzuki, Satoshi Kuwabara, Hiroyuki Akamine, Yosuke Onishi, Manato Yasuda, Yukiko Ozawa, Naoki Kawaguchi, Tomoya Kubota, Masanori P. Takahashi, Yasushi Suzuki, Genya Watanabe, Takashi Kimura, Takamichi Sugimoto, Makoto Samukawa, Naoya Minami, Masayuki Masuda, Shingo Konno, Yuriko Nagane, and Kimiaki Utsugisawa
Subjects: Alopecia, Non-motor symptoms, Refractory, Taste disorders, Thymoma, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. Methods We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. Results Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. Conclusion Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.
Published: 2024
Full Text: View/download PDF

3. 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
Full Text: View/download PDF

4. 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, Maki Terakawa, Satoshi Muneoka, Kazuhiro Nagahira, Yuriko Nagane, Jyoji Yamate, Masakatsu Motomura, and Kimiaki Utsugisawa
Subjects: Medicine, Science
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
Full Text: View/download PDF

5. Association between Glucocorticoid-Induced Osteoporosis and Myasthenia Gravis: A Cross-Sectional Study.

Author: Shingo Konno, Shigeaki Suzuki, Masayuki Masuda, Yuriko Nagane, Emiko Tsuda, Hiroyuki Murai, Tomihiro Imai, Toshiki Fujioka, Norihiro Suzuki, and Kimiaki Utsugisawa
Subjects: Medicine, Science
Abstract: To investigate the association between glucocorticoid-induced osteoporosis and myasthenia gravis (MG) using a cross-sectional survey in Japan.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.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.Glucocorticoid-induced osteoporosis aggravates quality of life in patients with MG.
Published: 2015
Full Text: View/download PDF

6. Insights into the classification of myasthenia gravis.

Author: Tetsuya Akaishi, Takuhiro Yamaguchi, Yasushi Suzuki, Yuriko Nagane, Shigeaki Suzuki, Hiroyuki Murai, Tomihiro Imai, Masakatsu Motomura, Kazuo Fujihara, Masashi Aoki, and Kimiaki Utsugisawa
Subjects: Medicine, Science
Abstract: Myasthenia gravis (MG) is often categorized into thymoma-associated MG, early-onset MG with onset age
Published: 2014
Full Text: View/download PDF

7. Three Types of Striational Antibodies in Myasthenia Gravis

Author: Shigeaki Suzuki, Kimiaki Utsugisawa, Yuriko Nagane, and Norihiro Suzuki
Subjects: Immunologic diseases. Allergy, RC581-607
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 on autoantibody status. 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
Full Text: View/download PDF

8. Headache Associated with Myasthenia Gravis: The Impact of Mild Ocular Symptoms

Author: Yoshinori Nishimoto, Shigeaki Suzuki, Kimiaki Utsugisawa, Yuriko Nagane, Mamoru Shibata, Toshihiko Shimizu, and Norihiro Suzuki
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2011
Full Text: View/download PDF

9. Therapeutic Responses to Efgartigimod for Generalized Myasthenia Gravis in Japan.

Author: Shigeaki Suzuki, Akiyuki Uzawa, Yuriko Nagane, Masayuki Masuda, Shingo Konno, Tomoya Kubota, Makoto Samukawa, Kei Ishizuchi, Daiki Tokuyasu, Hideo Handa, Manato Yasuda, Naoki Kawaguchi, Takashi Kimura, Yasushi Suzuki, Takamichi Sugimoto, Naoya Minami, Takahashi, Masanori P., Hiroyuki Murai, and Kimiaki Utsugisawa
Published: 2024
Full Text: View/download PDF

10. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study

Author: James F Howard, Saskia Bresch, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Kumaraswamy Sivakumar, Marek Śmiłowski, Kimiaki Utsugisawa, Tuan Vu, Michael D Weiss, Małgorzata Zajda, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W Duda, Romana Lowcock, Mark Vanderkelen, M Isabel Leite, Dylan Sembinelli, Jeanne Teitelbaum, Michael Nicolle, Emilien Bernard, Juliette Svahn, Marco Spinazzi, Tanya Stojkovic, Sophie Demeret, Nicolas Weiss, Loïc Le Guennec, Sihame Messai, Christine Tranchant, Aleksandra Nadaj-Pakleza, Jean-Baptiste Chanson, Muhtadi Suliman, Leila Zaidi, Celine Tard, Peggy Lecointe, Jana Zschüntzsch, Jens Schmidt, Stefanie Glaubitz, Rachel Zeng, Matthias Scholl, Markus Kowarik, Ulf Ziemann, Markus Krumbholz, Pascal Martin, Christoph Ruschil, Jutta Dünschede, Roswitha Kemmner, Natalie Rumpel, Benjamin Berger, Andreas Totzeck, Tim Hagenacker, Benjamin Stolte, Raffaele Iorio, Amelia Evoli, Silvia Falso, Carlo Antozzi, Rita Frangiamore, Fiammetta Vanoli, Elena Rinaldi, Kazushi Deguchi, Naoya Minami, Yuriko Nagane, Yasushi Suzuki, Sayaka Ishida, Shigeaki Suzuki, Jin Nakahara, Astushi Nagaoka, Shunsuke Yoshimura, Shingo Konno, Youko Tsuya, Akiyuki Uzawa, Tomoya Kubota, Masanori Takahashi, Tatsusada Okuno, Hiroyuki Murai, Nils Erik Gilhus, Marion Boldingh, Tone Hakvåg Rønning, Urszula Chyrchel-Paszkiewicz, Klaudiusz Kumor, Tomasz Zielinski, Krzysztof Banaszkiewicz, Michał Błaż, Agata Kłósek, Mariola Świderek-Matysiak, Andrzej Szczudlik, Aneta Paśko, Lech Szczechowski, Marta Banach, Jan Ilkowski, Solange Kapetanovic Garcia, Patricia Ortiz Bagan, Ana Belén Cánovas Segura, Joana Turon Sans, Nuria Vidal Fernandez, Elena Cortes Vicente, Patricia Rodrigo Armenteros, Mohammad Ashraghi, Ana Cavey, Liam Haslam, Anna Emery, Kore Liow, Sharon Yegiaian, Alexandru Barboi, Rosa Maria Vazquez, Joshua Lennon, Robert M Pascuzzi, Cynthia Bodkin, Sandra Guingrich, Adam Comer, Mark Bromberg, Teresa Janecki, Sami Saba, Marco Tellez, Bakri Elsheikh, Miriam Freimer, Sarah Heintzman, Raghav Govindarajan, Jeffrey Guptill, Janice M Massey, Vern Juel, Natalia Gonzalez, Ali A Habib, Tahseen Mozaffar, Manisha Korb, Namita Goyal, Hannah Machemehl, Georgios Manousakis, Jeffrey Allen, Emily Harper, Constantine Farmakidis, Lilli Saavedra, Mazen Dimachkie, Mamatha Pasnoor, Salma Akhter, Said Beydoun, Courtney McIlduff, Joan Nye, Bhaskar Roy, Bailey Munro Sheldon, Richard Nowak, Benjamin Barnes, Michael Rivner, Niraja Suresh, Jessica Shaw, Brittany Harvey, Lucy Lam, Nikki Thomas, Manisha Chopra, Rebecca E Traub, Sarah Jones, Mary Wagoner, Sejla Smajic, Radwa Aly, Jonathan Katz, Henry Chen, Robert G Miller, Liberty Jenkins, Shaida Khan, Bhupendra Khatri, Lisa Sershon, Pantelis Pavlakis, Shara Holzberg, Yuebing Li, Irys B Caristo, Robert Marquardt, Debbie Hastings, Jacob Rube, Robert P Lisak, Aparna Choudhury, Katherine Ruzhansky, Amit Sachdev, Susan Shin, Joan Bratton, Mary Fetter, Naya McKinnon, Jonathan McKinnon, Laura Sissons-Ross, Amos Sahu, and B Jane Distad
Subjects: Neurology (clinical)
Published: 2023
Full Text: View/download PDF

11. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study

Author: Vera Bril, Artur Drużdż, Julian Grosskreutz, Ali A Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, John Vissing, Tuan Vu, Marion Boehnlein, Ali Bozorg, Maryam Gayfieva, Bernhard Greve, Franz Woltering, Henry J Kaminski, Angela Genge, Rami Massie, Maxime Berube, Lubna Daniyal, Shabber Mannan, Eduardo Ng, Ritesh Rohan Raghu Raman, Evelyn Sarpong, Monica Alcantara, Annie Dionne, Zaeem Siddiqi, Derrick Blackmore, Faraz Hussain, Genevieve Matte, Stephan Botez, Michaela Tyblova, Michala Jakubikova, Jana Junkerova, Nanna Witting, Sonja Holm-Yildiz, Mads Stemmerik, Henning Andersen, Izabella Obál, Guilhem Solé, Stéphane Mathis, Marie-Hélène Violleau, Christine Tranchant, Sihame Messai, Jean-Baptiste Chanson, Aleksandra Nadaj-Pakleza, Arnaud Verloes, Leila Zaidi, Manuela Gambella, Michele Cavalli, Tanya Stojkovic, Sophie Demeret, Loic Le Guennec, Giorgia Querin, Nicolas Weiss, Marion Masingue, Laurent Magy, Karima Ghorab, Ia Rukhadze, Alexander Tsiskaridze, Marina Janelidze, Temur Margania, Florian Then Bergh, Eike Hänsel, Andrea Kalb, Bianca Meilick, Mandy Reuschel, Lars-Malte Teußer, Astrid Unterlauft, Clemens Goedel, Tim Hagenacker, Andreas Totzeck, Benjamin Stolte, Franz Blaes, Christine Bindler, Vasilios Tsoutsikas, Annekathrin Roediger, Christian Geis, Jens Schmidt, Jana Zschüntzsch, Margret Schwarz, Stefanie Meyer, Karsten Kummer, Stefanie Glaubitz, Rachel Zeng, Heinz Wiendl, Luisa Klotz, Anna Lammerskitten, Jan Lünemann, Péter Diószeghy, Lorenzo Maggi, Elena Rinaldi, Matteo Gastaldi, Federico Mazzacane, Pietro Businaro, Raffaele Iorio, Giovanni Antonini, Laura Fionda, Rita Rinaldi, Simone Rossi, Francesco Habetswallner, Francesco Tuccillo, Haruna Umehara, Eiko Uenaka, Masanori Takahashi, Keiko Higashi, Makoto Kinoshita, Emika Yoneda, Noriko Nakamura, Saeka Fujita, Tomoya Kubota, Masami Ono, Sana Yamamoto, Taku Hatano, Kazuki Oikoshi, Kazumasa Yokoyama, Yutaka Oji, Yuji Tomizawa, Akiyuki Uzawa, Manato Yasuda, Sachiko Akita, Yukiko Ozawa, Yosuke Onishi, Miki Takaki, Hiromi Yamada, Kanako Minemoto, Miki Sanko, Nanae Izawa, Mayumi Nakayama, Masayuki Masuda, Rune Tsuji, Nobuhiro Ido, Yumi Hyodo, Yoshihiko Okubo, Akiko Minohara, Nana Haraguchi, Makiko Naito, Seiko Yoshida, Yuri Fukushige, Akira Tsujino, Atsushi Nagaoka, Teiichiro Miyazaki, Shunsuke Yoshimura, Takuro Hirayama, Tomoaki Shima, Naoko Okamoto, Riki Matsumoto, Kenji Sekiguchi, Takehiro Ueda, Norio Chihara, Mari Kirimura, Emi Sunagawa, Ayaka Suzuki, Shigeaki Suzuki, Aozora Wada, Kei Ishizuchi, Yasushi Suzuki, Mitsuo Yata, Yuka Komatsu, Kenichi Tsukita, Genya Watanabe, Kazuki Sato, Emiko Kawasaki, Naoki Yamamoto, Hirohiko Ono, Tomoko Tsuda, Shigeki Ohashi, Yuka Fujisawa, Yumiko Yokota, Yuriko Nagane, Kameda Ayumi, Yuka Takematsu, Hiroyuki Naito, Kumiko Kuwada, Konrad Rejdak, Sebastian Szklener, Monika Kitowska, Kandyda Derkacz, Tomasz Berkowicz, Paulina Budzinska, Marek Halas, Leonid Zaslavskiy, Evgeniya Skornyakova, Sergey Kotov, Ekaterina Novikova, Olga Sidorova, Vitalii Goldobin, Tatiana Alekseeva, Patimat Isabekova, Nadezhda Malkova, Denis Korobko, Gordana Djordjevic, Aleksandar Stojanov, Stojan Peric, Dragana Lavrnic, Ivo Bozovic, Aleksa Palibrk, Carlos Casasnovas, Velina Nedkova-Hristova, Nuria Vidal Fernández, Elena Cortés Vicente, Luis Querol Gutiérrez, Maria Salvadó Figueras, Anna Canovas Segura, Raúl Juntas Morales, Daniel Sanchez Tejerina, Albert Saiz, Yolanda Blanco Morgado, Sara Llufriú Durán, María Sepúlveda Gázquez, Eugenia María Martínez Hernández, Gerardo Gutiérrez Gutiérrez, Paqui Iniesta, José Meca Lallana, Yuh-Cherng Guo, Hou-Chang Chiu, Jiann-Horng Yeh, Ya Hui Chen, Mei Fen Lee, Yi-Chung Lee, Kuan Lin Lai, Said Beydoun, Salma Akhter, Lucy Lam, Alisha Thomas, Michael Rivner, Brandy Quarles, Dale Lange, Shara Holzberg, Pantelis Pavlakis, Ashwathy Goutham, Henry Kaminski, Radwa Aly, Lisa Ashworth, Kathryn Bender, Karie Bond, Joanne Buckner, Sara Byerly, James Caress, Jessyca Clemons, Asha Farmer, Catherine Franklin, Summer Harris, Meredith Hiatt, Rachana Gandhi Mehta, Gina Miller, Lynn Smith, Rose Smith, Brian Strittmatter, Tahseen Mozaffar, Isela Hernandez, Kelsey Moulton, Chafic Karam, Pranali Ravikumar, Catherine Lomen-Hoerth, Laura Rosow, Hannah George, Viktoriya Irodenko, Carol Denny, Bart Hanson, Sara Klein, Jennifer Martinez-Thompson, Elie Naddaf, Denny Padgett, Eric Sorenson, Jane L Sultze, Delena Weis, Kourosh Rezania, Jason Thonhoff, Sheetal Shroff, Robert Pascuzzi, Angela Micheels, Cynthia Bodkin, Adam Comer, Gelasio Baras, Renee Wagner, Zabeen Mahuwala, Stephen Ryan, Kai Su, Khema Sharma, Andrew Brown, and Kore Liow
Subjects: Neurology (clinical)
Published: 2023
Full Text: View/download PDF

12. 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 Takahashi, Yasushi Suzuki, Genya Watanabe, Takashi Kimura, Takamichi Sugimoto, Makoto Samukawa, Naoya Minami, Masayuki Masuda, Shingo Konno, Yuriko Nagane, and Kimiaki Utsugisawa
Subjects: Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract: BackgroundEarly fast-acting treatment (EFT) is the aggressive use of fast-acting therapies such as plasmapheresis, intravenous immunoglobulin and/or intravenous high-dose methylprednisolone (IVMP) from the early phases of treatment. EFT is reportedly beneficial for early achievement of minimal manifestations (MM) or better status with ≤5 mg/day prednisolone (MM5mg), a practical therapeutic target for myasthenia gravis (MG).ObjectiveThe current study aimed to clarify which specific EFT regimen is efficacious and the patient characteristics that confer sensitivity to EFT.MethodsWe recruited a total of 1710 consecutive patients with MG who enrolled in the Japan MG Registry for this large-cohort study. Among them, 1066 with generalised MG who had received immunotherapy were analysed. Prognostic background factors were matched in a 1:1 ratio using propensity score matching analysis between patients treated with EFT (n=350) and those treated without EFT (n=350). The clinical course and time to first achieve MM5mg after starting immunotherapy was analysed in relation to treatment combinations and patient characteristics.ResultsKaplan-Meier analyses showed that EFT had a significant effect on the achievement of MM5mg (pConclusionEarly cycles of intervention with EFT and early use of calcineurin inhibitors provides long-term benefits in terms of achieving therapeutic targets for generalised MG, regardless of clinical subtype.
Published: 2023
Full Text: View/download PDF

13. Impact of Early Treatment with Intravenous High-Dose Methylprednisolone for Ocular Myasthenia Gravis

Author: Akiyuki Uzawa, Shigeaki Suzuki, Satoshi Kuwabara, Hiroyuki Akamine, Yosuke Onishi, Manato Yasuda, Yukiko Ozawa, Naoki Kawaguchi, Tomoya Kubota, Masanori P. Takahashi, Yasushi Suzuki, Genya Watanabe, Takashi Kimura, Takamichi Sugimoto, Makoto Samukawa, Naoya Minami, Masayuki Masuda, Shingo Konno, Yuriko Nagane, and Kimiaki Utsugisawa
Subjects: Pharmacology, Pharmacology (medical), Neurology (clinical)
Abstract: The efficacy of intravenous high-dose methylprednisolone (IVMP) in ocular myasthenia gravis (MG) has not been fully established. This study aimed to elucidate the effects of early intervention with IVMP for achieving the therapeutic targets (minimal manifestations [MM] or MM or better status with prednisolone ≤ 5 mg/day [MM5mg]) in ocular MG. In this observational study, we included a total of 1710 consecutive patients with MG enrolled in the Japan MG Registry in 2021. Of these, 204 patients with ocular MG who received immunotherapy were analyzed. The clinical course and time to first achieve MM or MM5mg after starting immunotherapy were compared between the early IVMP group (treated with IVMP within 3 months of treatment initiation) and the non-early IVMP group. Despite having greater clinical severity before immunotherapy and lower oral prednisolone doses throughout the course, the early IVMP group (n = 55) showed a higher rate of achievement of MM (P = 0.0040, log-rank test; hazard ratio 1.58, 95% confidence interval [CI] 1.13-2.20, P 0.0001) and MM5mg (P = 0.0005, log-rank test; hazard ratio 1.78, 95% CI 1.27-2.51, P 0.0001) compared with the non-early IVMP group (n = 149). In conclusion, an early intervention with IVMP is likely to increase the probability of achieving a better long-term outcome and reducing the total dose of corticosteroids in ocular MG.
Published: 2023
Full Text: View/download PDF

14. Japan <scp>MG</scp> registry: Chronological surveys over 10 years

Author: Shigeaki Suzuki, Masayuki Masuda, Akiyuki Uzawa, Yuriko Nagane, Shingo Konno, Yasushi Suzuki, Tomoya Kubota, Takamichi Sugimoto, Makoto Samukawa, Genya Watanabe, Kei Ishizuchi, Hiroyuki Akamine, Yosuke Onishi, Kazuki Yoshizumi, Takafumi Uchi, Itaru Amino, Yuki Ueta, Naoya Minami, Naoki Kawaguchi, Takashi Kimura, Masanori P. Takahashi, Hiroyuki Murai, and Kimiaki Utsugisawa
Subjects: Immunology and Microbiology (miscellaneous), Immunology, Neuroscience (miscellaneous), Neurology (clinical)
Published: 2022
Full Text: View/download PDF

15. 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
Full Text: View/download PDF

16. 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
Full Text: View/download PDF

17. 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
Full Text: View/download PDF

18. 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

19. 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
Full Text: View/download PDF

20. 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

21. 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
Full Text: View/download PDF

22. 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
Full Text: View/download PDF

23. 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: Kazumi Takada, Vladislav Abramov, Seiko Yoshida, Pinar Ozcelik, Carolina Miranda, Jennifer Kane, Kaitlyn McKenna, Natasha Campbell, Sharon P. Nations, Shitiz Kumar Sriwastava, Yuko Fujii, Mayumi Murata, Linda Wagemaekers, Angela Andoin, Mollie Vanderhook, Yoshinori Okubo, Martin Bilsker, Taira Uehara, Vera Bril, Julia Wanschitz, Stanislava Toncrova, Mariela Bettini, Kazumi Futono, Shachie Aranke, Yool-hee Kim, Hiroyuki Murai, Anne Nyrhinen, Vinay Chaudhry, Raffaele Iorio, Takashi Kanda, Brittany Harvey, Francisco Javier Rodriguez de Rivera, Henning Andersen, Marianne de Visser, Miwako Sato, Yasuhiro Maeda, Fabienne Deruelle, Marina Pozo, Adam Hart, Masaki Saitoh, Wladimir Bocca Vieira de Rezende Pinto, Said R. Beydoun, Lindsay Zilliox, Akihiro Mukaino, Cinzia Caserta, Mahi Jasinarachchi, Andrea M. Corse, Nikoletta Papadopoulou, JuYoung Kwon, Fernanda Carrara, Juliet Saba, Masayuki Makamori, Vittorio Frasca, Luciana Souza Duca, Hoo Nam Kang, C. Trebst, Celile Phan, Muzeyyen Ugur, Eduardo Ng, Jonathan McKinnon, Hila Bali Kuperman, David Feder, Judit Matolcsi, Jiri Pitha, Martin Stangel, Kate Beck, Gabriel Paiva, Diego Lopergolo, Katrien De Mey, Hidenori Matsuo, Lucas Eduardo Pazetto, Eugene Lai, Amanda Anderson, Ann D'Hondt, Tetsuya Akiyama, Beverly Fyfe, Bella Gross, Elisabet Arribas-Ibar, Kathy de Koning, Gulmohor Roy, Dmitry Pokhabov, Maria Johanna Keijzers, Nicholas Ventura, Tessa Marburger, John Loor, Ji Eun Lee, Alessandro Filla, Celal Tuga, Stephanie Scala, Rudy Mercelis, Marc H. De Baets, Hisako Kobayashi, Stanislav Vohanka, Ana Paula Macagnan, Ana Carolina Amaral de Andrade, Heike Arndt, Giovanni Antonini, Yumi Yamashita, Gwendal Le Masson, Sonia Garcia, Sarah Verjans, James F. Howard, Zaeem A. Siddiqi, Yuen T. So, Megumi Koga, Exuperio Diez Tejedor, Teresa Costabile, Mihoko Takada Takada, Steve Hopkins, Jonathan S. Katz, Charlene Hafer-Macko, Erica Nogueira Coelho, Hung Youl Seok, Carol Herbert, Yuriko Nagane, Didem Altiparmak, Sachiko Kamakura, Mohammad Sanjak, Caroline Moreau, Jordi Díaz-Manera, Sivakumar Sathasivam, Michael Vytopil, Amelia Evoli, Masakatsu Motomura, Ester Reggio, Guy Van den Abeele, Hélène Zéphir, Asya Yarmoschuk, Jasmine Hewlett, Amy Wilson, Sachie Fukui, Cavit Boz, Iandra Souza, Morgane Gaboreau, Ivana Jurajdova, Sonia Decressac, Yong Seo Koo, Valentina Pegoraro, Seung Min Kim, Benison Keung, Rosana Rocha, Nanna Witting, John Vissing, Elaine Weiner, Ali Malekniazi, Larisa Babenko, Amanda C. Guidon, Gal Maier, Charlotte Smetcoren, Robert M. Pascuzzi, Domenico Marco Bonifati, Yumiko Nakamura, Tamires Cristina Gomes da Silva, Takashi Murahara, Sarah Plevka, Tomoko Tsuda, John C. Kincaid, Arnaud Lacour, Ibrez Bandukwala, Alan R. Berger, Chang Nyoung Lee, Jae-Sung Lim, Vern C. Juel, Tulio E. Bertorini, Valeria Cavalcante Lino, Namie Taichi, Ju-Hong Min, Josep Gamez, Nelly Greenbereg, William S. David, Srikanth Muppidi, Husnu Efendi, Pedro Lopez Ruiz, Baki Dogan, Cansu Semiz, Natalia Julia Palacios, Sharon Downing, Paola Cudia, Daniel Jacobs, Can Ebru Bekircan-Kurt, Takayasu Fukudome, Kristen Roe, Lena Bjarbo, Nicole Kassebaum, Makoto Samukawa, Shizuka Asada, Christina Dheel, Fatima Maqsood, Eun Bi Hwang, Kevin Daniels, Sevim Erdem-Ozdamar, Olivier Stevens, Claudio Mazia, Karan Alcon, Sibel Gazioglu, Keiko Kikutake, Luis Lay, Petra Tilkin, Corrado Angelini, Derrick Blackmore, Kimiaki Utsugisawa, Despoina Charalambous, Tuula Harrison, Kristin Huynh, Huned S. Patwa, Laura Echevarria, Henrique Mohr, Christian Homedes-Pedret, Richard J. Barohn, Byung Jo Kim, Daniel DiCapua, Terry McClain, Debora Dada Martineli Torres, Maria Salvado Figueras, Ana Paula Melo, Riley Snook, Miki Ogawa, Marcelo Annes, Yuka Saito, Isabel Illa, Evanthia Bernitsas, Nicole Smalley, Molly Lindsay, Robert G. Miller, Olga Azrilin, Silvia Bonanno, Evgeniya Kosykh, Marcela Wolfova, Olivier Outteryck, Shirli Toska, Anna Kostera-Pruszczyk, HyeJin Ra, Rup Tandan, Sotirios Papagiannopoulos, Natasha Willlems, Anne Mette Ostergaard Autzen, Meinoshin Okumura, Patrick Vermersch, Sarada Sakamuri, Maria Antonia Alberti Aguilo, Shigemi Shimose, Cynthia Carter, Ira Blount, Lisa Thompson, Maurer Pereira Martins, Richard Nowak, Hyung Seok Lee, Anna Kaminska, Joan Bratton, Nazire Pinar Acar, Junichi Ogasawara, Mohamed Mahdi-Rogers, Teiichiro Mitazaki, Marek Čierny, Craig Donahue, Jaya Trivedi, Neelam Goyal, Gonzalo Vidal, Brandy Quarles, Akiko Kanzaki, Yasuko Ikeda, Tomomi Kobashikawa, Morris Brown, Daisuke Yamamoto, Michel Deneve, Denis Korobko, Beth DiSanzo, Benedikt Schoser, Heidi Boterhoven, Eri Kobayashi, Maoko Shirane, Cristiani Fernanda Butinhao, Eriko Higuchi, Takashi Hayashi, Masanori Takahashi, Anne-Cécile Wielanek-Bachelet, Benjamin Rix Brooks, Emanuela Onesti, Tahseen Mozaffar, Liang Lu, Sevasti Bostantzopoulou, Christophe Vial, Shawn J. Bird, Sandi Mumfrey-Thomas, Julie Khoury, Kara Patrick, Kenichi Tsukita, Yoshiko Sano, Hiroshi Nakazora, David P. Richman, Gavin Brown, Yoon-Ho Hong, Tomohiro Kawamura, Igor Dias Brockhausen, Ye Liu, Acary Souza Bulle Oliveira, Soichiro Funaka, Tomoya Hasuike, Frank Lin, Luis Antonio Querol Gutierrez, Namita Goyal, Elena Pinzan, Michelle Mellion, Silvia Messina, Christopher Lindberg, Csilla Rozsa, J. Chad Hoyle, Yoko Kaneko, Gustavo Duran, Francesco Patti, Arshira Seddigh, Ele Kim Perez, Jayashri Srinivasan, Michael Benatar, Philip Van Damme, Salma Akhter, Daniel Ambrosio, Maria Salvado, Floyd Jones, Mark Sivak, Anneke J. van der Kooi, Karen Callison, Catherine Nigro, Rebekah Garcia, Thomas Arnold, Hideki Arima, Brigid Crabtree, Mary Varghese, Aditya Kumar, Miri Kim, Fanny O'Brien, Naya McKinnon, Lauren Wheeler, Hong Vu, Shunsuke Yoshimura, Masatoshi Omoto, Jeffrey T. Guptill, Maria Gabriele, Francoise Bouhour, Veena Mathew, Ritsu Nakayama, Rosa Hasan, Francesco Saccà, Mohammed Salajegheh, Diana Dimitrova, Alzira Alves de Siqueira Carvalho, Maurizio Inghilleri, George Sachs, Rekha Pillai, Enrico Marano, Monika Konyane, Anh Tran, Seda Aydinlik, Kendrick Henderson, Fumie Meguro, Alexandre Guerreiro, Amaiak Chilingaryan, Tiyonnoh Cash, Jun Kawamata, Julie Steele, Helene Gervais-Bernard, Thomas Harbo, Alejandra Dalila Garcia, Musa Kazim Onar, Sabrina Sacconi, Carlos Casasnovas Pons, Nadezhda Malkova, Denis Sazonov, Mireya Fernandez-Fournier, Karin Fricke, Laurie Gutmann, Amy Saklad, Clara Schommer, Sandra Taber, Fiona Norwood, Tugce Kirbas Cavdar, Monique Miesen, Fernanda Troili, Masanori Watanabe, Ratna Bhavaraju-Sanka, Ted M. Burns, Sari Atula, Faisal Sohail, Barbora Kurkova, Brigitta Szabadosne, Luciana Renata Cubas Volpe, Jane Pedersen, Jing Jing Wang, Masashi Inoue, Antonella Di Pasquale, Megan Kramer, Magda Chmelikova, Mehran Soltani, Tuan Vu, Laura Fionda, Eliz Agopian, Susan Shin, Anthony A. Amato, Lotte Vinge, Hakan Cavus, Gil I. Wolfe, Joan Nye, Delphine Mahieu, Miguel Wilken, Markus Färkkilä, Catherine Faber, Erin Manning, Emiko Tsuda, Rami Massie, Paolo Emilio Alboini, Yasmeen Shabbir, Angela Campanella, Aikaterini Dimitriou, Marcelo Rugiero, Cynthia Bodkin, Gyorgyi Szabo, Sharon Halton, Akshay Shah, Yasuko Maeda, Hans D. Katzberg, Yagmur Caliskan, Jaimin Shah, Katsuhisa Masaki, Valentina Damato, Blanka Andersson, Aline de Cassia Santos, Masahiro Mori, Renato Mantegazza, Misa Shimpo, Joanne Nemeth, Livia Dezsi, Anna De Rosa, Doreen Ho, Julie Moutarde, Efstathia Mitropoulou, Amy Woodall, Angela Micheels, László Vécsei, Byoung Joon Kim, Lisa Smith, Tomihiro Imai, Harpreet Kaur, Lorenzo Maggi, Jane Distad, Anita Mogensen, Ericka Simpson, Anne Cooley, Eliana Reyes, Ha Young Shin, Da Yoon Koh, Stefan Gingele, Susan Strom, Ezgi Yilmaz, Manisha Chopra, Anna Melnikova, Edouard Millois, Ludwig Gutmann, Miriam Freimer, Hirokazu Shinozaki, Heena Olalde, Kerry Naunton, Shunya Nakane, Ihsan Sengun, Dimos-Dimitrios Mitsikostas, Edina Varga, Juha-Pekka Erälinna, Wolfgang Löscher, Jan De Bleecker, Elena Bravver, Ana Lazaro, Eun Bin Cho, Thomas Cochrane, Jonathan Goldstein, Lisa D. Hobson-Webb, Michaela Tyblova, Angela Marsil, J. Edward Hartmann, Miyuki Morikawa, Karen Zakalik, Claude Desnuelle, Iveta Novakova, Michiaki Koga, Melinda Horvath, Luiz Otavio Maia Gonçalves, Elena Cortes Vicente, Alejandro Tobon Gonzalez, Stanley H. Appel, Brian Minton, Daniele Orrico, Brian Droker, Jacob Kaufman, Erica Coelho, Chafic Karam, Mikko Laaksonen, Katherine Amato, Jinmyoung Seok, Natalia Prando, Pauline Lahaut, Kaori Osakada, Phillipa Lamont, Alexandros Tselis, Daiane da Cruz Pacheco, Joan Højgaard, Hirokazu Shiraishi, Josef Bednarik, Stefania Morino, Mark Levine-Weinberg, Sara-Claude Michon, Yusuke Fukuda, Michael Pulley, Koichi Narikawa, Ricardo Rojas Garcia, Betsy Mosmiller, James Gilchrist, Maria da Penha Morita Ananias, Maryanne Burdette, Shingo Konno, Janelle Butters, Stephan Wenninger, Debbie Davies, Thomas Skripuletz, Mohammad Alsharabati, Katarina Reguliova, Gabor Lovas, Yuichiro Gondo, Miju Shin, HyeLim Lee, Bruno Bezerra Rosa, Michael D. Weiss, Martha Zampaki, Andrea Caramma, Jeffrey V. Rosenfeld, Cigdem Ozen Aydin, Shara Holzberg, Hélène Merle, Olga Zapletalova, Kurt-Wolfram Suehs, Robert P. Lisak, Dale J. Lange, Albert Hietala, Sedat Sen, Elena Giacomelli, Akiyuki Uzawa, Tomás Augusto Suriane Fialho, Matteo Garibaldi, Nadia Sattar, Wai-Kuen Leong, Lindsay Kaplan, Tetsuya Kanai, Jaana Eriksson, Akiko Nagaishi, Khema Sharma, Tamar Gibson, Mohamed Kazamel, Yulia Nesterova, Sascha Alvermann, Murat Terzi, Taylor Darnell, Donna Carnes, Victor Balyazin, John T. Kissel, Waqar Waheed, Jana Junkerova, Kimberly Robeson, Nicholas Vlaikidis, Nicholas Silvestri, Fredrik Piehl, Maurício André Gheller Friedrich, Shun Shimohama, Nuria Vidal, Eleni Kasioti, H. James Jones, Michael K. Hehir, Luiz Augusto da Silva, Dave Watling, Leslie Roberts, Casey Faigle, Caroline Hourquin, Olli Oksaranta, Tomomi Imamura, Shin Hisahara, Dennis Jeffery, Marie-Hélène Soriani, M. Kawai, Chieko Yoshikawa, Roseann Keo, Angela Genge, Michelangelo Maestri Tassoni, Milvia Pleitez, Michael H. Rivner, Maki Jingu, Giorgia Puorro, Andrea Swenson, Saiju Jacob, Carolina Ortea, Shuichiro Suzuki, Marguerite Engel, Ikuko Kamegamori, SangAe Park, Guilhem Sole, Lesly Welsh, Nichole Gallatti, Jakit Gollogly, Daniel Jons, Yasuteru Sano, Takuya Matsushita, Omar Khan, Maria Cristina Gori, Thabata Veiga, Julie Agriesti, Jos Maessen, Sandra Guinrich, Francesca Bevilacqua, Laura Haar, Jordana Gonçalves Geraldo, Justin Y. Kwan, Hidekazu Suzuki, Dai Matsuse, Kelly Jia, Ozlem Tun, Lara Katzin, Yasushi Suzuki, Shannon Lucy, Carlo Antozzi, ANS - Neuroinfection & -inflammation, Neurology, Howard, James F, Utsugisawa, Kimiaki, Benatar, Michael, Murai, Hiroyuki, Barohn, Richard J, Illa, Isabel, Jacob, Saiju, Vissing, John, Burns, Ted M, Kissel, John T, Muppidi, Srikanth, Nowak, Richard J, O'Brien, Fanny, Wang, Jing-Jing, Mantegazza, Renato, Mazia, Claudio Gabriel, Wilken, Miguel, Ortea, Carolina, Saba, Juliet, Rugiero, Marcelo, Bettini, Mariela, Vidal, Gonzalo, Garcia, Alejandra Dalila, Lamont, Phillipa, Leong, Wai-Kuen, Boterhoven, Heidi, Fyfe, Beverly, Roberts, Leslie, Jasinarachchi, Mahi, Willlems, Natasha, Wanschitz, Julia, Löscher, Wolfgang, De Bleecker, Jan, Van den Abeele, Guy, de Koning, Kathy, De Mey, Katrien, Mercelis, Rudy, Wagemaekers, Linda, Mahieu, Delphine, Van Damme, Philip, Smetcoren, Charlotte, Stevens, Olivier, Verjans, Sarah, D'Hondt, Ann, Tilkin, Petra, Alves de Siqueira Carvalho, Alzira, Hasan, Rosa, Dias Brockhausen, Igor, Feder, David, Ambrosio, Daniel, Melo, Ana Paula, Rocha, Rosana, Rosa, Bruno, Veiga, Thabata, Augusto da Silva, Luiz, Gonçalves Geraldo, Jordana, da Penha Morita Ananias, Maria, Nogueira Coelho, Erica, Paiva, Gabriel, Pozo, Marina, Prando, Natalia, Dada Martineli Torres, Debora, Fernanda Butinhao, Cristiani, Coelho, Erica, Renata Cubas Volpe, Luciana, Duran, Gustavo, Gomes da Silva, Tamires Cristina, Otavio Maia Gonçalves, Luiz, Pazetto, Lucas Eduardo, Souza Duca, Luciana, Suriane Fialho, Tomás Augusto, Gheller Friedrich, Maurício André, Guerreiro, Alexandre, Mohr, Henrique, Pereira Martins, Maurer, da Cruz Pacheco, Daiane, Macagnan, Ana Paula, de Cassia Santos, Aline, Bulle Oliveira, Acary Souza, Amaral de Andrade, Ana Carolina, Annes, Marcelo, Cavalcante Lino, Valeria, Pinto, Wladimir, Miranda, Carolina, Carrara, Fernanda, Souza, Iandra, Genge, Angela, Massie, Rami, Campbell, Natasha, Bril, Vera, Katzberg, Han, Soltani, Mehran, Ng, Eduardo, Siddiqi, Zaeem, Phan, Celile, Blackmore, Derrick, Vohanka, Stanislav, Bednarik, Josef, Chmelikova, Magda, Cierny, Marek, Toncrova, Stanislava, Junkerova, Jana, Kurkova, Barbora, Reguliova, Katarina, Zapletalova, Olga, Pitha, Jiri, Novakova, Iveta, Tyblova, Michaela, Wolfova, Marcela, Jurajdova, Ivana, Andersen, Henning, Harbo, Thoma, Vinge, Lotte, Mogensen, Anita, Højgaard, Joan, Witting, Nanna, Autzen, Anne Mette, Pedersen, Jane, Färkkilä, Marku, Atula, Sari, Nyrhinen, Anne, Erälinna, Juha-Pekka, Laaksonen, Mikko, Oksaranta, Olli, Eriksson, Jaana, Harrison, Tuula, Desnuelle, Claude, Sacconi, Sabrina, Soriani, Marie-Hélène, Decressac, Sonia, Moutarde, Julie, Lahaut, Pauline, Solé, Guilhem, Le Masson, Gwendal, Wielanek-Bachelet, Anne-Cécile, Gaboreau, Morgane, Moreau, Caroline, Wilson, Amy, Vial, Christophe, Bouhour, Françoise, Gervais-Bernard, Helene, Merle, Hélène, Hourquin, Caroline, Lacour, Arnaud, Outteryck, Olivier, Vermersch, Patrick, Zephir, Hélène, Millois, Edouard, Deneve, Michel, Deruelle, Fabienne, Schoser, Benedikt, Wenninger, Stephan, Stangel, Martin, Alvermann, Sascha, Gingele, Stefan, Skripuletz, Thoma, Suehs, Kurt-Wolfram, Trebst, Corinna, Fricke, Karin, Papagiannopoulos, Sotirio, Bostantzopoulou, Sevasti, Vlaikidis, Nichola, Zampaki, Martha, Papadopoulou, Nikoletta, Mitsikostas, Dimos-Dimitrio, Kasioti, Eleni, Mitropoulou, Efstathia, Charalambous, Despoina, Rozsa, Csilla, Horvath, Melinda, Lovas, Gabor, Matolcsi, Judit, Szabo, Gyorgyi, Szabadosne, Brigitta, Vecsei, Laszlo, Dezsi, Livia, Varga, Edina, Konyane, Monika, Gross, Bella, Azrilin, Olga, Greenbereg, Nelly, Bali Kuperman, Hila, Antonini, Giovanni, Garibaldi, Matteo, Morino, Stefania, Troili, Fernanda, Di Pasquale, Antonella, Filla, Alessandro, Costabile, Teresa, Marano, Enrico, Sacca, Francesco, Marsili, Angela, Puorro, Giorgia, Maestri Tassoni, Michelangelo, De Rosa, Anna, Bonanno, Silvia, Antozzi, Carlo, Maggi, Lorenzo, Campanella, Angela, Angelini, Corrado, Cudia, Paola, Pegoraro, Valentina, Pinzan, Elena, Bevilacqua, Francesca, Orrico, Daniele, Bonifati, Domenico Marco, Evoli, Amelia, Alboini, Paolo Emilio, D'Amato, Valentina, Iorio, Raffaele, Inghilleri, Maurizio, Fionda, Laura, Frasca, Vittorio, Giacomelli, Elena, Gori, Maria, Lopergolo, Diego, Onesti, Emanuela, Gabriele, Maria, Patti, Francesco, Salvatore Caramma, Andrea, Messina, Silvia, Reggio, Ester, Caserta, Cinzia, Uzawa, Akiyuki, Kanai, Tetsuya, Mori, Masahiro, Kaneko, Yoko, Kanzaki, Akiko, Kobayashi, Eri, Masaki, Katsuhisa, Matsuse, Dai, Matsushita, Takuya, Uehara, Taira, Shimpo, Misa, Jingu, Maki, Kikutake, Keiko, Nakamura, Yumiko, Sano, Yoshiko, Nagane, Yuriko, Kamegamori, Ikuko, Fujii, Yuko, Futono, Kazumi, Tsuda, Tomoko, Saito, Yuka, Suzuki, Hidekazu, Morikawa, Miyuki, Samukawa, Makoto, Kamakura, Sachiko, Shiraishi, Hirokazu, Mitazaki, Teiichiro, Motomura, Masakatsu, Mukaino, Akihiro, Yoshimura, Shunsuke, Asada, Shizuka, Kobashikawa, Tomomi, Koga, Megumi, Maeda, Yasuko, Takada, Kazumi, Takada, 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 Kooi, Anneke, de Visser, Marianne, Gibson, Tamar, Maessen, Jo, de Baets, Marc, Faber, Catherine, Keijzers, Maria Johanna, Miesen, Monique, Kostera-Pruszczyk, Anna, Kaminska, Anna, Kim, Byung-Jo, Lee, Chang Nyoung, Koo, Yong Seo, Seok, Hung Youl, Kang, Hoo Nam, Ra, Hyejin, Kim, Byoung Joon, Cho, Eun Bin, Lee, Hyelim, Min, Ju-Hong, Seok, Jinmyoung, Koh, Da Yoon, Kwon, Juyoung, Lee, Jieun, Park, Sangae, Hong, Yoon-Ho, Lim, Jae-Sung, Kim, Miri, Kim, Seung Min, Kim, Yool-hee, Lee, Hyung Seok, Shin, Ha Young, Hwang, Eun Bi, Shin, Miju, Sazonov, Deni, Yarmoschuk, Asya, Babenko, Larisa, Malkova, Nadezhda, Melnikova, Anna, Korobko, Deni, Kosykh, Evgeniya, Pokhabov, Dmitry, Nesterova, Yulia, Abramov, Vladislav, Balyazin, Victor, Casasnovas Pons, Carlo, Alberti Aguilo, Maria, Homedes-Pedret, Christian, Palacios, Natalia Julia, Lazaro, Ana, Diez Tejedor, Exuperio, Fernandez-Fournier, Mireya, Lopez Ruiz, Pedro, Rodriguez de Rivera, Francisco Javier, Salvado Figueras, Maria, Gamez, Josep, Salvado, Maria, Cortes Vicente, Elena, Diaz-Manera, Jordi, Querol Gutierrez, Lui, Rojas Garcia, Ricardo, Vidal, Nuria, Arribas-Ibar, Elisabet, Piehl, Fredrik, Hietala, Albert, Bjarbo, Lena, Lindberg, Christopher, Jons, Daniel, Andersson, Blanka, Sengun, Ihsan, Ozcelik, Pinar, Tuga, Celal, Ugur, Muzeyyen, Boz, Cavit, Altiparmak, Didem, Gazioglu, Sibel, Ozen Aydin, Cigdem, Erdem-Ozdamar, Sevim, Bekircan-Kurt, Can Ebru, Yilmaz, Ezgi, Acar, Nazire Pinar, Caliskan, Yagmur, Efendi, Husnu, Aydinlik, Seda, Cavus, Hakan, Semiz, Cansu, Tun, Ozlem, Terzi, Murat, Dogan, Baki, Onar, Musa Kazim, Sen, Sedat, Cavdar, Tugce Kirba, Norwood, Fiona, Dimitriou, Aikaterini, Gollogly, Jakit, Mahdi-Rogers, Mohamed, Seddigh, Arshira, Maier, Gal, Sohail, Faisal, Sathasivam, Sivakumar, Arndt, Heike, Davies, Debbie, Watling, Dave, Rivner, Michael, Hartmann, J. 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
Full Text: View/download PDF

24. 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

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

Author: Gil I. Wolfe, Reza Sadjadi, Kelly G. Gwathmey, Kimiaki Utsugisawa, Changyi Ou, Shahriar Nafissi, Vera Bril, Karissa L. Gable, Masayuki Masuda, Amruta Joshi, Carolina Barnett, Jean-Yves Hogrel, Vern C. Juel, Caroline Carmichael, Hiroyuki Murai, Donald B. Sanders, Nicholas Silvestri, Janice M. Massey, Gary Cutter, Sarah M. Jones, Weibin Liu, Maria Elena Farrugia, Yuriko Nagane, Simone Birnbaum, Mark R. Conaway, Lisa D. Hobson-Webb, Farzad Fatehi, Jeffrey T. Guptill, and Ted M. Burns
Subjects: 0301 basic medicine, medicine.medical_specialty, Rasch model, Psychometrics, Physiology, business.industry, Person location, Quality of life scale, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mg qol15, 030104 developmental biology, 0302 clinical medicine, Physical medicine and rehabilitation, Disease severity, Quality of life, Physiology (medical), medicine, Physical therapy, Neurology (clinical), Hrqol instrument, business, 030217 neurology & neurosurgery
Abstract: Introduction 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. Methods We first performed Rasch analysis on >1,300 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 on >1,300 MG-QOL15r scales. Results 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. Conclusions 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
Full Text: View/download PDF

26. 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

27. 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
Full Text: View/download PDF

28. 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

29. 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

30. 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

31. 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
Full Text: View/download PDF

32. 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

33. Contents Vol. 71, 2014

Author: Masaki Yazawa, Yukiko Hata, Hideyuki Tomita, Zhaolu Wang, Giancarlo Di Battista, Claudio Gasperini, Jill Abrigo, Lulu Zhou, Chiara Rosa Mancinelli, Xinfeng Liu, Hisao Ogata, Maria Grazia Grasso, Luca Prosperini, Hussien Heshmat Kassem, Laurent Tatu, Gelin Xu, Heejin Kim, Ding Bang Chen, Agnès Jacquin, Ka Sing Wong, Yuriko Nagane, Wenshan Sun, Tomohisa Nagasao, Reham Shamloul, Joëlle Hamblin, Xiu Ling Liang, Yang Kun Chen, Suk Jae Kim, M. Hervieu, Maurice Giroud, Renato P. Munhoz, Shu Yang Lu, Vincent Mok, Yan Guo, Sara Collorone, A. Jacquin, Diego Centonze, Giovanni Frisullo, Naoki Nishida, Thierry Ettlin, Francisco Cardoso, Lanlan Wang, Wusheng Zhu, Tatiana Koudriavtseva, Gabor S. Ungvari, Yannick Béjot, O. Rouaud, Koshi Kinoshita, Liang Ge, George Liu, Magali Laidet, Claude Touzery, Hélio A.G. Teive, Oh Young Bang, Yun Liao, Yunfei An, Dong Hoon Shin, Stéphane Armand, Hua Li, M.-E. Virat-Brassaud, Yunyun Xiong, Minmin Ma, M. Ménassa, Pasquale Calabrese, Ryota Tamura, Qiankun Cai, Patrice H. Lalive, Norihiro Suzuki, Yeonsil Moon, Shigeaki Suzuki, M. Giroud, Tomihiro Imai, Ada Francia, C. Aboa-Eboulé, Michel Chofflon, Yongkun Li, Satz Mengensatzproduktion, Seol-Heui Han, Yun Li, Xun Hua Li, Gilles Allali, Druckerei Stückle, Assem Hashad, Hans J. Markowitsch, Marianne Zeller, Qin Yin, Xiaobing Fan, Hiroyuki Murai, Fabio Buttari, Veronica Villani, Shunichi Shimizu, Hirotaka Katoh, Min Li, Mitsuru Kawamura, Emiko Tsuda, Adel Zaki, Katsuhiro Mizutani, Maud Maza, Foad Abd-Allah, Xiao-pei Sun, Xiang Xin Liu, Xuan Liu, Carlo Pozzilli, F. Ricolfi, Antonio Carota, Won-Jin Moon, Li Feng, Winnie C.W. Chu, Lixin Li, Vanessa Fernandez, Wai Kwong Tang, Yui Takeuchi, Yi Li, Yves Cottin, Tomoru Miwa, Simona Pontecorvo, Qizhang Wang, Yan-wei Miao, Jung Seok Lee, Jung-Kook Song, Maurizio Paciaroni, Ji Man Hong, Benoit Daubail, Xiaomeng Wang, Yusuke Shimizu, Le Hou, Maho Takagi, Dezhi Liu, Masakazu Ishii, Peter Flachenecker, Young Ook Noh, Wen Sun, Rezanejad Nasim, G.-V. Osseby, Simonetta Galgani, Lin Huan Huang, Frédéric Assal, Kimiaki Utsugisawa, Zhaoyao Chen, Sung Il Sohn, Jin Soo Lee, Ming Li, Kazuo Kishi, Alessandro Clemenzi, Uwe K. Zettl, Xinying Fan, Xiao-fei Ji, Jiangtao Tang, and Thomas Henze
Subjects: Neurology, Neurology (clinical)
Published: 2014
Full Text: View/download PDF

34. 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
Full Text: View/download PDF

35. 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
Full Text: View/download PDF

36. 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
Full Text: View/download PDF

37. 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

38. 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

39. [Japan MG Registry Study: A Sophisti- cated Multi-center Study of Myasthe- nia Gravis A sophisticated multi-center Study of Myasthenia Gravis]

Author: Hiroyuki, Murai, Kimiaki, Utsugisawa, Shigeaki, Suzuki, Yuriko, Nagane, Tomihiro, Imai, Masakatsu, Motomura, and Jun-ichi, Kira
Subjects: Japan, Early Medical Intervention, Myasthenia Gravis, Practice Guidelines as Topic, Quality of Life, Humans, Multicenter Studies as Topic, Registries
Published: 2016

40. 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

41. 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
Full Text: View/download PDF

42. 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
Full Text: View/download PDF

43. 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
Full Text: View/download PDF

44. 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
Full Text: View/download PDF

45. 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
Full Text: View/download PDF

46. 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
Full Text: View/download PDF

47. 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
Full Text: View/download PDF

48. 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
Full Text: View/download PDF

49. [Quality of life and advice for lifestyle in myasthenia gravis]

Author: Yuriko, Nagane and Kimiaki, Utsugisawa
Subjects: Sleep Wake Disorders, Depression, Myasthenia Gravis, Disease Progression, Quality of Life, Humans, Life Style
Published: 2015

50. 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

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

119 results on '"Yuriko Nagane"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources