12 results on '"Sazonov, Denis V"'
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2. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
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Bar-Or, Amit, Wiendl, Heinz, Montalban, Xavier, Alvarez, Enrique, Davydovskaya, Maria, Delgado, Silvia R., Evdoshenko, Evgeniy P., Giedraitiene, Natasa, Gross-Paju, Katrin, Haldre, Sulev, Herrman, Craig E., Izquierdo, Guillermo, Karelis, Guntis, Leutmezer, Fritz, Mares, Miroslav, Meca-Lallana, Jose Eustasio, Mickeviciene, Dalia, Nicholas, Jacqueline, Robertson, Derrick S., Sazonov, Denis V., Sharlin, Kenneth, Sundaram, Bharathy, Totolyan, Natalia, Vachova, Marta, Valis, Martin, Bagger, Morten, Häring, Dieter A., Ludwig, Inga, Willi, Roman, Zalesak, Martin, Su, Wendy, Merschhemke, Martin, Fox, Edward J., Universitat Autònoma de Barcelona, Institut Català de la Salut, [Bar-Or A] Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [Wiendl H] Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany. [Montalban X] Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Alvarez E] Department of Neurology, Rocky Mountain MS Center, University of Colorado, Aurora, CO, USA. [Davydovskaya M] Pirogov Russian National Research Medical University, Moscow, Russian Federation. [Delgado SR] MS Center and Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA, and Vall d'Hebron Barcelona Hospital Campus
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Multiple Sclerosis ,medicine.drug_class ,Injections, Subcutaneous ,Otros calificadores::Otros calificadores::/inducido químicamente [Otros calificadores] ,Phases of clinical research ,Esclerosi múltiple ,Pharmacology ,Bioequivalence ,Ofatumumab ,Monoclonal antibody ,Antibodies, Monoclonal, Humanized ,Multiple sclerosis ,chemistry.chemical_compound ,Pharmacokinetics ,autoinjector pen ,bioequivalence ,multiple sclerosis ,pharmacokinetics ,pre-filled syringe ,medicine ,Humans ,business.industry ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES] ,Antibodies, Monoclonal ,Injeccions hipodèrmiques ,medicine.disease ,Autoinjector pen ,B cell depletion ,Neurology ,chemistry ,Pre-filled syringe ,Other subheadings::Other subheadings::/chemically induced [Other subheadings] ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] ,Neurology (clinical) ,business ,Anticossos monoclonals - Abstract
Ofatumumab; Multiple sclerosis; Pharmacokinetics Ofatumumab; Esclerosis múltiple; Farmacocinética Ofatumumab; Esclerosi múltiple; Farmacocinètica Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the APLIOS trial was funded by Novartis Pharmaceuticals. Novartis Pharmaceuticals supported the development of this manuscript, provided data analyses according to the direction of the authors, and paid for medical writing support.
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- 2021
3. sj-docx-1-msj-10.1177_13524585211055934 ��� Supplemental material for Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study
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Kira, Jun-ichi, Nakahara, Jin, Sazonov, Denis V, Kurosawa, Takayoshi, Tsumiyama, Isao, Willi, Roman, Zalesak, Martin, Pingili, Ratnakar, H��ring, Dieter A, Ramanathan, Krishnan, Kieseier, Bernd C, Merschhemke, Martin, Su, Wendy, and Saida, Takahiko
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FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-msj-10.1177_13524585211055934 for Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study by Jun-ichi Kira, Jin Nakahara, Denis V Sazonov, Takayoshi Kurosawa, Isao Tsumiyama, Roman Willi, Martin Zalesak, Ratnakar Pingili, Dieter A H��ring, Krishnan Ramanathan, Bernd C Kieseier, Martin Merschhemke, Wendy Su and Takahiko Saida in Multiple Sclerosis Journal
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- 2021
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4. sj-docx-1-msj-10.1177_13524585211044479 – Supplemental material for Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
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Bar-Or, Amit, Wiendl, Heinz, Montalban, Xavier, Alvarez, Enrique, Davydovskaya, Maria, Delgado, Silvia R, Evdoshenko, Evgeniy P, Giedraitiene, Natasa, Gross-Paju, Katrin, Haldre, Sulev, Herrman, Craig E, Izquierdo, Guillermo, Karelis, Guntis, Leutmezer, Fritz, Mares, Miroslav, Meca-Lallana, Jose E, Mickeviciene, Dalia, Nicholas, Jacqueline, Robertson, Derrick S, Sazonov, Denis V, Sharlin, Kenneth, Sundaram, Bharathy, Totolyan, Natalia, Vachova, Marta, Valis, Martin, Bagger, Morten, Häring, Dieter A, Ludwig, Inga, Willi, Roman, Zalesak, Martin, Su, Wendy, Merschhemke, Martin, and Fox, Edward J
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FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-msj-10.1177_13524585211044479 for Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study by Amit Bar-Or, Heinz Wiendl, Xavier Montalban, Enrique Alvarez, Maria Davydovskaya, Silvia R Delgado, Evgeniy P Evdoshenko, Natasa Giedraitiene, Katrin Gross-Paju, Sulev Haldre, Craig E Herrman, Guillermo Izquierdo, Guntis Karelis, Fritz Leutmezer, Miroslav Mares, Jose E Meca-Lallana, Dalia Mickeviciene, Jacqueline Nicholas, Derrick S Robertson, Denis V Sazonov, Kenneth Sharlin, Bharathy Sundaram, Natalia Totolyan, Marta Vachova, Martin Valis, Morten Bagger, Dieter A Häring, Inga Ludwig, Roman Willi, Martin Zalesak, Wendy Su, Martin Merschhemke and Edward J Fox in Multiple Sclerosis Journal
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- 2021
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5. Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study.
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Kira, Jun-ichi, Nakahara, Jin, Sazonov, Denis V, Kurosawa, Takayoshi, Tsumiyama, Isao, Willi, Roman, Zalesak, Martin, Pingili, Ratnakar, Häring, Dieter A, Ramanathan, Krishnan, Kieseier, Bernd C, Merschhemke, Martin, Su, Wendy, and Saida, Takahiko
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MULTIPLE sclerosis ,PLACEBOS ,OPPORTUNISTIC infections ,MONOCLONAL antibodies ,AFRICAN swine fever - Abstract
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Sustained Efficacy of Ofatumumab in Relapsing Multiple Sclerosis Patients: Results from Extended Treatment in the Phase 2 APOLITOS Study (2032)
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Saida, Takahiko, primary, Nakahara, Jin, additional, Sazonov, Denis V., additional, Kurosawa, Takayoshi, additional, Tsumiyama, Isao, additional, Willi, Roman, additional, Zalesak, Martin, additional, Pingili, Ratnakar, additional, Häring, Dieter A., additional, Ramanathan, Krishnan, additional, Su, Wendy, additional, and Kira, Jun-ichi, additional
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- 2021
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7. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.
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Bar-Or, Amit, Wiendl, Heinz, Montalban, Xavier, Alvarez, Enrique, Davydovskaya, Maria, Delgado, Silvia R, Evdoshenko, Evgeniy P, Giedraitiene, Natasa, Gross-Paju, Katrin, Haldre, Sulev, Herrman, Craig E, Izquierdo, Guillermo, Karelis, Guntis, Leutmezer, Fritz, Mares, Miroslav, Meca-Lallana, Jose E, Mickeviciene, Dalia, Nicholas, Jacqueline, Robertson, Derrick S, and Sazonov, Denis V
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MULTIPLE sclerosis ,MONOCLONAL antibodies ,SYRINGES - Abstract
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC
τ ) and maximum plasma concentration (Cmax ) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ , 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax , 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion. [ABSTRACT FROM AUTHOR]- Published
- 2022
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8. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial
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Palace, Jacqueline, primary, Wingerchuk, Dean M., additional, Fujihara, Kazuo, additional, Berthele, Achim, additional, Oreja-Guevara, Celia, additional, Kim, Ho Jin, additional, Nakashima, Ichiro, additional, Levy, Michael, additional, Terzi, Murat, additional, Totolyan, Natalia, additional, Viswanathan, Shanthi, additional, Wang, Kai-Chen, additional, Pace, Amy, additional, Yountz, Marcus, additional, Miller, Larisa, additional, Armstrong, Róisín, additional, Pittock, Sean, additional, Muñoz, Daniel Julio, additional, Amor, Jorge David, additional, Bocchiardo, Carolina, additional, Danielle, Julieta Iourno, additional, Laffue, Alfredo, additional, Obregon, Carolina Daniela Diaz, additional, Paez, Maria Fernanda, additional, Perez, Roberto Martin, additional, Rocchi, Viviana Ana Maria, additional, Teijeiro, Loreley Deborah, additional, Gómez, Jesica, additional, Villa, Andres Maria, additional, Aguirre, Florencia, additional, Fernández, Victoria Carla, additional, Goicoechea, Ramon F., additional, Melamud, Luciana, additional, Stillman, Ana, additional, de Virgiliis, Mariana, additional, Cassara, Fatima Pagani, additional, Cordoba, Marta, additional, Gutierrez, Maria Teresa, additional, Ingolotti, Mariana, additional, Larripa, Natalia, additional, Lupinacci, Anahi, additional, Arroyo, Josefina, additional, Romano, Alejandra, additional, Torres, Mariana Foa, additional, Ballario, Carlos Héctor, additional, Chiesa, Ana Elisa, additional, Gómez, Hernán Gustavo, additional, Lattini, Hernán Gabriel, additional, Mainella, Carolina Natalia, additional, Bolner, Gisel Edith, additional, Eschoyez, María Soledad, additional, Broadley, Simon Andrew, additional, Heshmat, Saman, additional, Sabet, Arman, additional, Swayne, Andrew, additional, Freeman, Susan, additional, Sanchez, Sofia Jimenez, additional, Shuey, Neil, additional, Dalic, Linda, additional, French, Ann, additional, Kuma, Guru, additional, Laing, Joshua, additional, Law, Lai Yin, additional, MacIntyre, Jennifer, additional, Neal, Andrew, additional, Plummer, Christopher, additional, Ramachandran, Prashanth, additional, Sedal, Leslie, additional, Wilson, Ian, additional, Winkel, Antony, additional, Zhang, Wenwen, additional, Chen, Tina, additional, Watts, Rani, additional, Barnett, Michael, additional, Barton, Joshua, additional, Beadnall, Heidi, additional, Garber, Justin, additional, Hardy, Todd Andrew, additional, Trewin, Benjamin, additional, Taha, Marinda, additional, Walters, Deleni, additional, Sieger, Federico Arturo Silva, additional, Alfonso, Nhora Patricia Ruiz, additional, Camacho, Anna Maria Pinzon, additional, Moreno, Alexander Pabón, additional, Prad, Jorge Armando Castellanos, additional, Rueda, Adriana Paola Duarte, additional, Castillo, Tatiana, additional, Gonzalez, Karol Melissa Castillo, additional, Pico, Martha Yolanda Moreno, additional, Castill, Judith, additional, Habek, Mario, additional, Adamec, Ivan, additional, Barun, Barbara, additional, Crnosija, Luka, additional, Gabelic, Tereza, additional, Nytrova, Petra, additional, Krasulova, Eva, additional, Pavlickova, Jana, additional, Tyblova, Michaela, additional, Zubkova, Jana, additional, Petersen, Thor, additional, Dale, Gro Helen, additional, Rasmussen, Peter Vestergaard, additional, Stilund, Morten, additional, Svendsen, Kristina Bacher, additional, Brandt, Vivi, additional, Collongues, Nicolas, additional, Fleury, Marie-Celine, additional, Kremer, Laurent, additional, Bendele, Sandrine, additional, Neff, Valérie, additional, Diem, Ricarda, additional, Platten, Michael, additional, Berberich, Anne, additional, Jansen, Jonabelle, additional, Jaschoneck, Hannah, additional, Wildemann, Brigitte, additional, Aures, Ursula, additional, Brandenburger, Tanja, additional, Haut, Tanja, additional, Fernández, Maria-Lourdes Treceno, additional, Aly, Lilian, additional, Brinkhoff, Kirsten, additional, Buck, Dorothea, additional, Golkowski, Daniel, additional, Hermisson, Mirjam, additional, Hoshi, Muna-Miriam, additional, Kaminski, Miriam, additional, Kowarik, Markus Christian, additional, Kronsbein, Helena, additional, Lehmann-Horn, Klaus, additional, Pongratz, Viola Maria, additional, Schweiker, Andreas, additional, Leddy, Lisa-Ann, additional, Mueller, Silvia, additional, Obergfell, Kim, additional, Wanka, Marion, additional, Zettl, Uwe Klaus, additional, Klinke, Jan, additional, Loebermann, Micha, additional, Meister, Stefanie, additional, Rimmele, Florian, additional, Winkelmann, Alexander, additional, Schroeder, Ina, additional, Lau, Alexander Yuk-Lun, additional, Au, Lisa Wing-Chi, additional, Fan, Florence Sin-Ying, additional, Ip, Vincent Hing-Lung, additional, Ma, Karen Ka-Yan, additional, Ma, Sze-Ho, additional, Mok, Vincent Chung-Tong, additional, Au, Cheryl Chung-Kwan, additional, Kwan, Pauline Wing-Lam, additional, Patti, Francesco, additional, Caramma, Andrea Salvatore, additional, Chisari, Clara Grazia, additional, Fermo, Salvatore Lo, additional, Messina, Silvia, additional, Projetto, Maria, additional, Caserta, Cinzia, additional, Filla, Alessandro, additional, Costabile, Teresa, additional, Pane, Chiara, additional, Sacca, Francesco, additional, Marsili, Angela, additional, Puorro, Giorgia, additional, Bergamaschi, Roberto, additional, Berra, Eliana, additional, Mallucci, Giulia, additional, Fattore, Cinzia, additional, Gasperini, Claudio, additional, Galgani, Simonetta, additional, Haggiag, Shalom, additional, Ruggieri, Serena, additional, Vento, Claudio, additional, Quartuccio, Esmeralda Maria, additional, Pozzilli, Carlo, additional, Barletta, Valeria Teresa, additional, Borriello, Giovanna, additional, De Giglio, Laura, additional, Marinelli, Fabiana, additional, Tasillo, Miriam, additional, Amadori, Alessandra, additional, Fischetti, Mariano, additional, Gurreri, Flavia, additional, Mori, Masahiro, additional, Masuda, Hiroki, additional, Ohtani, Ryohei, additional, Sekiguchi, Yukari, additional, Uchida, Tomohiko, additional, Uzawa, Akiyuki, additional, Ito, Hiromi, additional, Kabasawa, Emi, additional, Kaneko, Yoko, additional, Matsushita, Takuya, additional, Matsuse, Dai, additional, Murai, Hiroyuki, additional, Hayashi, Shintaro, additional, Masak, Katsuhisa, additional, Ogata, Hidenori, additional, Shinoda, Koji, additional, Uehara, Taira, additional, Watanabe, Mitsuru, additional, Yamaguchi, Hiroo, additional, Yamasaki, Ryo, additional, Yonekawa, Tomomi, additional, Jingu, Maki, additional, Nagano, Makiko, additional, Nakamura, Yumiko, additional, Sano, Yoshiko, additional, Araki, Manabu, additional, Lin, Youwei, additional, Mori, Madoka, additional, Mukai, Yohei, additional, Sano, Terunori, additional, Sato, Wakiro, additional, Gogun, Naoya, additional, Maeda, Yuriko, additional, Nishimoto, Asami, additional, Tsukamoto, Sachiko, additional, Yanagi, Ritsuko, additional, Saida, Takahiko, additional, Nakamura, Shinichi, additional, Nasu, Tetsuya, additional, Saida, Kyoko, additional, Shikata, Yuko, additional, Kodani, Yoshimi, additional, Saeki, Megumi, additional, Sawada, Yukako, additional, Yoshikawa, Hiroo, additional, Kimura, Takashi, additional, Nishi, Masamitsu, additional, Sakamoto, Shun, additional, Ukon, Shinichiro, additional, Watanabe, Shohei, additional, Ebisuya, Saori, additional, Kimura, Nami, additional, Matsuura, Manami, additional, Morisaki, Yukie, additional, Muroi, Yoshiko, additional, Onishi, Kuniko, additional, Oshima, Ikuko, additional, Washino, Yuki, additional, Yamashita, Tomomi, additional, Misu, Tatsuro, additional, Kaneko, Kimihiko, additional, Kato, Masaaki, additional, Kuroda, Hiroshi, additional, Kurosawa, Kazuhiro, additional, Nishiyama, Shuhei, additional, Ono, Hirohiko, additional, Takai, Yoshiki, additional, Abe, Keiko, additional, Hoshi, Hitomi, additional, Jinushi, Mari, additional, Oyama, Azusa, additional, Sakuma, Motonari, additional, Sawada, Yuko, additional, Ishibashi, Satoru, additional, Yokota, Takanori, additional, Nishida, Yoichiro, additional, Ozaki, Kokoro, additional, Sanjo, Nobuo, additional, Sato, Nozomu, additional, Denno, Fuki, additional, Hiraki, Haruko, additional, Matsubara, Yumi, additional, Kanda, Takashi, additional, Abe, Masaaki, additional, Honda, Masaya, additional, Kawai, Motoharu, additional, Koga, Michiaki, additional, Maeda, Toshihiko, additional, Ogasawara, Junichi, additional, Omoto, Masatoshi, additional, Sano, Yasuteru, additional, Sato, Ryota, additional, Shimizu, Fumitaka, additional, Arima, Hideki, additional, Fukui, Sachie, additional, Ishikawa, Yoshiko, additional, Koyama, Tomoko, additional, Shimose, Shigemi, additional, Shinozaki, Hirokazu, additional, Watanabe, Masanori, additional, Yasuda, Sachi, additional, Yoshiwaka, Chieko, additional, Adenan, Suffian, additional, Aris, Mohd Azman M, additional, Mawardi, Ahmad Shahir bin, additional, Adnan, Muhammad Al Hafiz, additional, Munusamy, Nanthini, additional, Razali, Siti Nur Omaira, additional, Somasundram, Punitha, additional, Hyun, Jae Won, additional, Jeong, In Hye, additional, Kim, Su-Hyun, additional, Shin, Hyun-June, additional, Yoo, Ji Sung, additional, Jang, HyunMin, additional, Joung, AeRan, additional, Kim, Byung-Jo, additional, Baek, Seol-Hee, additional, Kim, Jung Bin, additional, Kim, Yoo Hwan, additional, Koo, Yong Seo, additional, Lee, Chan Nyoung, additional, Seok, Hung Youl, additional, Hwang, Jinhee, additional, Kim, Sung Min, additional, Ahn, So Hyun, additional, Choi, Kyomin, additional, Choi, Seok-Jin, additional, Kim, Jun-Soon, additional, Kwon, Young Nam, additional, Shin, Je-Young, additional, Kwon, Hyeonju, additional, Kim, Byoung Joon, additional, Cho, Eun Bin, additional, Cho, Hye-Jin, additional, Choi, Misong, additional, Kim, DongSun, additional, Kim, Ju Hyeon, additional, Ki, SeungJu, additional, Lee, Hye Lim, additional, Lee, Kwang-Ho, additional, Min, Ju-Hong, additional, Park, Ji-Hyung, additional, Seok, Jinmyoung, additional, Choi, Eunhwa, additional, Park, Sang Ae, additional, Kim, Seung Min, additional, Jeong, Ha-Neul, additional, Jeongbin, Bong, additional, Jung, Jin Woo, additional, Kim, Seung Woo, additional, Kim, Yool-hee, additional, Lee, Hyung Seok, additional, Shin, Ha Young, additional, Jung, Yeon, additional, Kim, Min Jung, additional, Lee, Nou Ri, additional, Shin, MiJu, additional, Khabirov, Farit A, additional, Averyanova, Lyudmila, additional, Babicheva, Natalya, additional, Granatov, Eugenii, additional, Kazarov, Sergey, additional, Khaybullin, Timur, additional, Rogozhin, Alexander, additional, Pokhabov, Dmitry V, additional, Abramov, Vladislav, additional, Amelina, Anastasia, additional, Nesteroca, Yulia, additional, Bozhenkina, Tatyana, additional, Boyko, Aleksey N, additional, Demyan, Elena G, additional, Khoroshilova, Inessa, additional, Melnikov, Mikhail, additional, Popova, Ekaterina V, additional, Sharanova, Svetlana N, additional, Shchur, Sergey G, additional, Sazonov, Denis V, additional, Babenko, Larisa, additional, Bayandina, Elena, additional, Yarmoschuk, Asya, additional, Baliazin, Victor A, additional, Baliazina, Elena, additional, Budaeva, Elena, additional, Chernikova, Irina, additional, Goncharova, Zoya, additional, Krasnov, Vladimir, additional, Myatleva, Marina, additional, Rodionova, Olga V., additional, Samulyzhko, Iuliana, additional, Timofeeva, Alla A., additional, Duran, Sabas Boyero, additional, Bilbao, Maria Mar Mendibe, additional, Cuervo, Irene Diaz, additional, Domingo, Jose Maria Losada, additional, Eizaguirre, Amaia Gonzalez, additional, Llona, Jose Eulalio Barcena, additional, Moyano, Roberto Valverde, additional, Bahamonde, Carmen, additional, Lopez, Fernando Sanchez, additional, Morales, Raquel Pinar, additional, Morales, Eduardo Agüera, additional, Roman, Carmen Bahamonde, additional, Sepulveda, Juan Jose Ochoa, additional, Valero, Maria del Carmen Blanco, additional, Viña, Nazaret Pelaez, additional, Gavilan, Cristina Conde, additional, Sanchez, Ana Maria Jover, additional, Bedmar, Sara Vila, additional, Garcia, Nuria Gonzalez, additional, Garcia, Aida Orviz, additional, Gonzalez-Suarez, Ines, additional, Guillamon, Elena Miñano, additional, Kawiorski, Miguel, additional, Schulz, Elena Guerra, additional, Alonso, Alba Garcia, additional, Perez, Francisco Jesus Lopez, additional, Sarmiento, Marta Palacios, additional, Ayuso, Guillermo Izquierdo, additional, Mascarell, Guillermo Navarro, additional, Camino, Cristina Paramo, additional, Garcia, Asuncion Varas, additional, Mendoza, Yaiza Montserrat, additional, Muñoz, Veronica Ines Vargas, additional, Tonda, Patricia Torres, additional, Tsai, Ching-Piao, additional, Yin, Jiu-Haw, additional, Chen, Mei-Jung, additional, Li, Shan-Ni, additional, Wang, Fei-Ti, additional, Srisuwannanukorn, Suwat, additional, Boonmongkol, Thanatat, additional, Borisutbuathip, Duangporn, additional, Singwicha, Duangkamol, additional, Siritanan, Krittika, additional, Thearapati, Chidchanoke, additional, Sornda, Kwanmuang, additional, Apiwattanakul, Metha, additional, Aungsumart, Saharat, additional, Suanprasert, Narupat, additional, Suksuchano, Kaona, additional, Parkinsee, Nittaya, additional, Kulkantrakorn, Kongkiat, additional, Lolekha, Praween, additional, Potigumjon, Artit, additional, Sukphulloprat, Puchit, additional, Suksasunee, Dararat, additional, Komaratat, Chankawee, additional, Luangtong, Sunattana, additional, Arayawichanont, Arkhom, additional, Konpan, Phanpaphon, additional, Riablershirun, Nathapol, additional, Wiroteurairuang, Thaddao, additional, Jantaweesirirat, Panadda, additional, Kurne, Aslı, additional, Erkent, Irem, additional, Kurt, Ebru Bekircan, additional, Saylam, Ezgi, additional, Caliskan, Yagmur, additional, Orsel, Gulsah, additional, Celik, Yahya, additional, Celebi, Canan, additional, Tekatas, Aslan, additional, Banbal, Tugce, additional, Demir, Gulsen Akman, additional, Altunrende, Burcu, additional, Matur, Zeliha, additional, Topcular, Baris, additional, Elmas, Tules, additional, Gulo, Aysenur, additional, Ozdemir, Selin, additional, Ozkoklesen, Cansu, additional, Ozturk, Mahinur, additional, Yanik, Mertkan, additional, Yildirim, Elif, additional, Tutuncu, Melih, additional, Altintas, Ayse, additional, Cam, Abdulsamet, additional, Elmali, Ayse Deniz, additional, Saip, Sabahattin, additional, Siva, Aksel, additional, Tanrıverdi, Uygur, additional, Uygunoglu, Ugur, additional, Caliskan, Sinem, additional, Gulo, Pinar, additional, Kozig, Esra, additional, Sakiz, Sakine, additional, Sengun, Ihsan Sukru, additional, Idiman, Egemen, additional, Ala, Rahmi Tumay, additional, Arslan, Duygu, additional, Bulut, Utku, additional, Karakaptan, Yasemin, additional, Kaya, Derya, additional, Mehdiyev, Zaur, additional, Balkan, Bengu, additional, Kuku, Berfu, additional, Ozhun, Mujgan, additional, Tuga, Celal, additional, Ugur, Muzeyyen, additional, Efendi, Husnu, additional, Bunul, Sena Destan, additional, Cavus, Hakan, additional, Gorke, Yunus Emre, additional, Kutlu, Ayse, additional, Ozturk, Seda, additional, Sarikaya, Cansu Egilmez, additional, Becerikli, Gulsah, additional, Semiz, Cansu, additional, Tun, Ozlem, additional, Ayer, Sehriban, additional, Onar, Musa Kazim, additional, Ozberk, Mehlika Berra, additional, Sen, Sedat, additional, Cavdar, Tugce Kirbas, additional, Veske, Adife, additional, Boz, Cavit, additional, Altiparmak, Didem, additional, Aydin, Cigdem Ozen, additional, Gazioglu, Sibel, additional, Bekircan, Duygu, additional, Jacob, Anu, additional, Arndt, Heike, additional, Elsone, Liene, additional, Hamid, Shahd Hassan Mahmoud, additional, Whittam, Daniel Hugh, additional, Wilson, Martin, additional, O'Brien, Imelda, additional, Leite, Maria Isabel da Silva, additional, Cruz, Pedro Maria Rodriguez, additional, Jenkins, Damian Robert, additional, Tackley, George, additional, Cavey, Ana, additional, Everett, Rosie, additional, Hodder, Joy, additional, Koelewyn, Abigail, additional, Mowry, Ellen, additional, Royal, Walter, additional, Shin, Robert, additional, Bever, Christopher, additional, Harrison, Daniel, additional, Rus, Horea, additional, Zheng, Wei, additional, Callison, Karen, additional, Naunton, Kerry, additional, Frishberg, Benjamin M, additional, Blumenfeld, Andrew M, additional, Inocelda, Andrew, additional, Korabathina, Kalyani, additional, Lobatz, Michael, additional, Mortin, Melissa M, additional, Oh, Irene J, additional, Rosenberg, Jay H, additional, Sadoff, Mark, additional, Sahagian, Gregory A, additional, Wang, Anchi, additional, Camberos, Yasmin, additional, Sanchez, Guadalupe, additional, Soto, Estela, additional, Nicholas, Jacqueline A, additional, Boster, Aaron, additional, Eubank, Geoffrey, additional, Groezinger, Katy, additional, Lauf, Meghan, additional, Okai, Annette F, additional, Hasan, Rashedul, additional, Khoury, Chaouki, additional, Stokes, Victoria, additional, Clardy, Stacey, additional, Cortez, Melissa, additional, Greenlee, John, additional, Rose, John, additional, Soldan, Mateo Paz, additional, Emett, Amanda, additional, Esquibel, Lawanda, additional, Fagatele, Lilly, additional, Wong, Ka-Ho, additional, Stevens, James C, additional, Banas, Thomas M, additional, Bultemeyer, Marlene C, additional, Haller, Andrea, additional, Manalo, Natalie, additional, Aeschliman, Keri, additional, Kocks, Debi, additional, Racke, Michael, additional, Boster, Aaron Lee, additional, Bowman, Michelle, additional, Imitola, Jaime, additional, Kisanuki, Yasushi, additional, Green, Misty, additional, Scarberry, Stephanie, additional, Lynch, Sharon G, additional, Anderson, Heather S, additional, Gronseth, Gary S, additional, Hammond, Nancy E, additional, Jassam, Yasir N, additional, Mittal, Manoj K, additional, Nashatizadeh, Muhammed M, additional, Levine, Nicholas, additional, Schmidt, Lisa, additional, Sibley, Jill, additional, Whitley, Vonda, additional, Winkley, James, additional, Coleman, Timothy, additional, Cooper, Gregory, additional, Sheffield, Stephanie, additional, Turner, Keri, additional, Galloway, Dana, additional, Tillett, Robert S, additional, Ganesh, Geeta A, additional, Plato, Brian M, additional, Seifert, Tad D, additional, Godwin, Diana, additional, Lockridge, Deborah, additional, Rammohan, Kottil W, additional, Sheremata, William A, additional, Delgado, Silvia, additional, Gonzalez, Jose, additional, Lizarraga, Alexis, additional, Maldonado, Janice, additional, Ortega, Melissa, additional, Tornes, Leticia, additional, Babcock, Yanet, additional, Cailam, Osmara, additional, Campos, Yesica, additional, Couvertier, Irlisse, additional, Daneri, Bettina, additional, Deni, Jeremy, additional, Hernandez, Jeffrey, additional, Jaramillo, Tatiana, additional, Morris, Tenita, additional, Nobel, Daniel, additional, Oliveira, Anjelis, additional, Richardson, Reshma, additional, Rodriguez, Gloria, additional, Romero, Ana, additional, Sandova, Carlos, additional, Sawant, Ruta, additional, Tueros, Lissett, additional, Zetka, Eric S, additional, Zheng, Chao, additional, Jacobs, Daniel H, additional, Easterling, Constance, additional, Fairbank, Jennifer, additional, Iyengar, Revathi, additional, Klafter, Mark, additional, Lindquist, Justin, additional, Sadek, Ahmed H, additional, Toro, Elizabeth Carmona, additional, Verma, Navin, additional, Castro, Brigith Patino, additional, Sukhraj-Singh, Nadia, additional, Berger, Joseph, additional, Williamson, Eric, additional, Chahin, Salim, additional, Jacobs, Dina, additional, Markowitz, Clyde, additional, Dobbins, Jessica, additional, Mace, Lauren, additional, Martin, Maria, additional, Pinckney, Ashley, additional, Roberts, Amber, additional, Zaydan, Islam, additional, Mitchell, Galen W, additional, Heyman, Rock A, additional, Orie, Ryan L, additional, Suski, Valerie R, additional, Oddis, Kerry, additional, Punjack, Darlene, additional, Flanagan, Eoin, additional, Gadoth, Avi, additional, McKeon, Andrew, additional, Tobin, W Oliver, additional, Zekeridou, Anastasia, additional, Dunlay, Katie, additional, Sagen, Jessica, additional, Carter, Jonathan L, additional, Estephan, Bachir, additional, Goodman, Brent P, additional, Snyder, Charlene R Hoffman, additional, Francone, Andrea, additional, Galasky, Irene, additional, Thomas, Martha, additional, Repovic, Pavle, additional, Bowen, James, additional, Mayadev, Angeli, additional, Qian, Peiqing, additional, Courtney, Yuriko, additional, Lennox, Lauren, additional, Naismith, Robert Thomas, additional, Cross, Anne Haney, additional, Evans, Emily, additional, Longbrake, Erin E, additional, Orchard, Megan E, additional, Wu, Gregory F, additional, Heinrich, Linda, additional, Sommers, Susan, additional, Amjad, Faria, additional, Mitchell, Erika, additional, Mora, Carlos, additional, Schreiber, Bethany, additional, Tornatore, Carlo, additional, Carlson, Alexis, additional, McCarthy, Sacha, additional, and Oliver, Alexandria, additional
- Published
- 2021
- Full Text
- View/download PDF
9. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- Author
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Kappos, Ludwig, primary, Bar-Or, Amit, additional, Cree, Bruce A C, additional, Fox, Robert J, additional, Giovannoni, Gavin, additional, Gold, Ralf, additional, Vermersch, Patrick, additional, Arnold, Douglas L, additional, Arnould, Sophie, additional, Scherz, Tatiana, additional, Wolf, Christian, additional, Wallström, Erik, additional, Dahlke, Frank, additional, Achiron, Anat, additional, Achtnichts, Lutz, additional, Agan, Kadriye, additional, Akman-Demir, Gulsen, additional, Allen, Alison B, additional, Antel, Jack P, additional, Antiguedad, Alfredo Rodriguez, additional, Apperson, Michelle, additional, Applebee, Angela M, additional, Ayuso, Guillermo Izquierdo, additional, Baba, Masayuki, additional, Bajenaru, Ovidiu, additional, Balasa, Rodica, additional, Balci, Belgin Petek, additional, Barnett, Michael, additional, Bass, Ann, additional, Becker, Veit U, additional, Bejinariu, Mihaela, additional, Bergh, Florian Then, additional, Bergmann, Arnfin, additional, Bernitsas, Evanthia, additional, Berthele, Achim, additional, Bhan, Virender, additional, Bischof, Felix, additional, Bjork, Randall John, additional, Blevins, Gregg, additional, Boehringer, Matthias, additional, Boerner, Thomas, additional, Bonek, Robert, additional, Bowen, James D, additional, Bowling, Allen, additional, Boyko, Alexey N, additional, Boz, Cavit, additional, Bracknies, Vera, additional, Braune, Stefan, additional, Brescia Morra, Vincenzo, additional, Brochet, Bruno, additional, Brola, Waldemar, additional, Brownstone, Paul Kenneth, additional, Brozman, Miroslav, additional, Brunet, Donald, additional, Buraga, Ioan, additional, Burnett, Margaret, additional, Buttmann, Mathias, additional, Butzkueven, Helmut, additional, Cahill, Jonathan, additional, Calkwood, Jonathan C, additional, Camu, William, additional, Cascione, Mark, additional, Castelnovo, Giovani, additional, Centonze, Diego, additional, Cerqueira, Joao, additional, Chan, Andrew, additional, Cimprichova, Andrea, additional, Cohan, Stanley, additional, Comi, Giancarlo, additional, Conway, Jill, additional, Cooper, Joanna A, additional, Corboy, John, additional, Correale, Jorge, additional, Costell, Brian, additional, Cottrell, David A, additional, Coyle, Patricia K, additional, Craner, Matthew, additional, Cui, Liying, additional, Cunha, Luis, additional, Czlonkowska, Anna, additional, da Silva, Ana Martins, additional, de Sa, Joao, additional, de Seze, Jérôme, additional, Debouverie, Marc, additional, Debruyne, Jan, additional, Decoo, Danny, additional, Defer, Gilles, additional, Derfuss, Tobias, additional, Deri, Norma H, additional, Dihenia, Bhupesh, additional, Dioszeghy, Peter, additional, Donath, Vladimir, additional, Dubois, Benedicte, additional, Duddy, Martin, additional, Duquette, Pierre, additional, Edan, Gilles, additional, Efendi, Husnu, additional, Elias, Stanton, additional, Emrich, Peter J, additional, Estruch, Bonaventura Casanova, additional, Evdoshenko, Evgeniy P, additional, Faiss, Juergen, additional, Fedyanin, Alexander S, additional, Feneberg, Wolfgang, additional, Fermont, Jiske, additional, Fernandez, Oscar Fernandez, additional, Ferrer, Francisco Coret, additional, Fink, Katharina, additional, Ford, Helen, additional, Ford, Corey, additional, Francia, Ada, additional, Freedman, Mark, additional, Frishberg, Benjamin, additional, Galgani, Simonetta, additional, Garmany, George P, additional, Gehring, Klaus, additional, Gitt, Jeffrey, additional, Gobbi, Claudio, additional, Goldstick, Lawrence P, additional, Gonzalez, Rafael Arroyo, additional, Grandmaison, Francois, additional, Grigoriadis, Nikolaos, additional, Grigorova, Olga, additional, Grimaldi, Luigi Maria Edoardo, additional, Gross, Jeffrey, additional, Gross-Paju, Katrin, additional, Gudesblatt, Mark, additional, Guillaume, Daniel, additional, Haas, Judith, additional, Hancinova, Viera, additional, Hancu, Anca, additional, Hardiman, Orla, additional, Harmjanz, Arndt, additional, Heidenreich, Fedor R, additional, Hengstman, G J D, additional, Herbert, Joseph, additional, Herring, Mark, additional, Hodgkinson, Suzanne, additional, Hoffmann, Olaf M, additional, Hofmann, Werner E, additional, Honeycutt, William D, additional, Hua, Le Hanh, additional, Huang, Dehui, additional, Huang, Yining, additional, Huang, DeRen, additional, Hupperts, Raymond, additional, Imre, Piroska, additional, Jacobs, Alan Keith, additional, Jakab, Gabor, additional, Jasinska, Elzbieta, additional, Kaida, Kenichi, additional, Kalnina, Jolanta, additional, Kaprelyan, Ara, additional, Karelis, Guntis, additional, Karussis, Dimitrios, additional, Katz, Amos, additional, Khabirov, Farit A, additional, Khatri, Bhupendra, additional, Kimura, Takashi, additional, Kister, Ilya, additional, Kizlaitiene, Rasa, additional, Klimova, Eleonora, additional, Koehler, Juergen, additional, Komatineni, Aparna, additional, Kornhuber, Anselm, additional, Kovacs, Krisztina, additional, Koves, Agnes, additional, Kozubski, Wojciech, additional, Krastev, Georgi, additional, Krupp, Lauren B, additional, Kurca, Egon, additional, Lassek, Christoph, additional, Laureys, Guy, additional, Lee, Liesly, additional, Lensch, Eckart, additional, Leutmezer, Fritz, additional, Li, Hongzeng, additional, Linker, Ralf A, additional, Linnebank, Michael, additional, Liskova, Petra, additional, Llanera, Cristina, additional, Lu, Jiahong, additional, Lutterotti, Andreas, additional, Lycke, Jan, additional, Macdonell, Richard, additional, Maciejowski, Maciej, additional, Maeurer, Mathias, additional, Magzhanov, Rim V, additional, Maida, Eva-Maria, additional, Malciene, Lina, additional, Mao-Draayer, Yang, additional, Marfia, Girolama Alessandra, additional, Markowitz, Clyde, additional, Mastorodimos, Vasileios, additional, Matyas, Klotild, additional, Meca-Lallana, Jose, additional, Merino, Juan Antonio Garcia, additional, Mihetiu, Ioan Gheorghe, additional, Milanov, Ivan, additional, Miller, Aaron E, additional, Millers, Andrejs, additional, Mirabella, Massimiliano, additional, Mizuno, Masanori, additional, Montalban, Xavier, additional, Montoya, Lilina, additional, Mori, Masahiro, additional, Mueller, Stefanie, additional, Nakahara, Jin, additional, Nakatsuji, Yuji, additional, Newsome, Scott, additional, Nicholas, Richard, additional, Nielsen, A Scott, additional, Nikfekr, Esmaeil, additional, Nocentini, Ugo, additional, Nohara, Chiyoko, additional, Nomura, Kyoichi, additional, Odinak, Miroslav M, additional, Olsson, Tomas, additional, van Oosten, B W, additional, Oreja-Guevara, Celia, additional, Oschmann, Patrick, additional, Overell, James, additional, Pachner, Andrew, additional, Panczel, Gyula, additional, Pandolfo, Massimo, additional, Papeix, Caroline, additional, Patrucco, Liliana, additional, Pelletier, Jean, additional, Piedrabuena, Raul, additional, Pless, Misha, additional, Polzer, Udo, additional, Pozsegovits, Krisztian, additional, Rastenyte, Daiva, additional, Rauer, Sebastian, additional, Reifschneider, Gerd, additional, Rey, Roberto, additional, Rizvi, Syed A, additional, Robertson, Derrick, additional, Rodriguez, Jose Martinez, additional, Rog, David, additional, Roshanisefat, Homayoun, additional, Rowe, Vernon, additional, Rozsa, Csilla, additional, Rubin, Susan, additional, Rusek, Stanislaw, additional, Saccà, Francesco, additional, Saida, Takahiko, additional, Salgado, Antonio Vasco, additional, Sanchez, Victoria Eugenia Fernandez, additional, Sanders, Kalina, additional, Satori, Maria, additional, Sazonov, Denis V, additional, Scarpini, Elio Angelo, additional, Schlegel, Eugen, additional, Schluep, Myriam, additional, Schmidt, Stephan, additional, Scholz, Erich, additional, Schrijver, H M, additional, Schwab, Matthias, additional, Schwartz, Raymond, additional, Scott, James, additional, Selmaj, Krzysztof, additional, Shafer, Stuart, additional, Sharrack, Basil, additional, Shchukin, Ivan A, additional, Shimizu, Yuko, additional, Shotekov, Penko, additional, Siever, Arno, additional, Sigel, Karl-Otto, additional, Silliman, Scott, additional, Simo, Magdolna, additional, Simu, Mihaela, additional, Sinay, Vladimiro, additional, Siquier, Antonio Escartin, additional, Siva, Aksel, additional, Skoda, Ondrej, additional, Solomon, Andrew, additional, Stangel, Martin, additional, Stefoski, Dusan, additional, Steingo, Brian, additional, Stolyarov, Igor D, additional, Stourac, Pavel, additional, Strassburger-Krogias, Katrin, additional, Strauss, Erik, additional, Stuve, Olaf, additional, Tarnev, Ivaylo, additional, Tavernarakis, Antonios, additional, Tello, Cristina Ramo, additional, Terzi, Murat, additional, Ticha, Veronika, additional, Ticmeanu, Marina, additional, Tiel-Wilck, Klaus, additional, Toomsoo, Toomas, additional, Tubridy, Niall, additional, Tullman, Mark J, additional, Tumani, Hayrettin, additional, Turcani, Peter, additional, Turner, Ben, additional, Uccelli, Antonio, additional, Urtaza, Francisco Javier Olascoaga, additional, Vachova, Marta, additional, Valikovics, Attila, additional, Walter, Silke, additional, Van Wijmeersch, Bart, additional, Vanopdenbosch, Ludo, additional, Weber, Joerg R, additional, Weiss, Sara, additional, Weissert, Robert, additional, West, Timothy, additional, Wiendl, Heinz, additional, Wiertlewski, Sandrine, additional, Wildemann, Brigitte, additional, Willekens, Barbara, additional, Visser, L H, additional, Vorobeychik, Galina, additional, Xu, Xianhao, additional, Yamamura, Takashi, additional, Yang, Yi N, additional, Yelamos, Sergio Martinez, additional, Yeung, Michael, additional, Zacharias, Alan, additional, Zelkowitz, Marvin, additional, Zettl, Uwe, additional, Zhang, Meini, additional, Zhou, Hongyu, additional, Zieman, Ulf, additional, and Ziemssen, Tjalf, additional
- Published
- 2018
- Full Text
- View/download PDF
10. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- Author
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Ludwig Kappos, Amit Bar-Or, Bruce A C Cree, Robert J Fox, Gavin Giovannoni, Ralf Gold, Patrick Vermersch, Douglas L Arnold, Sophie Arnould, Tatiana Scherz, Christian Wolf, Erik Wallström, Frank Dahlke, Anat Achiron, Lutz Achtnichts, Kadriye Agan, Gulsen Akman-Demir, Alison B Allen, Jack P Antel, Alfredo Rodriguez Antiguedad, Michelle Apperson, Angela M Applebee, Guillermo Izquierdo Ayuso, Masayuki Baba, Ovidiu Bajenaru, Rodica Balasa, Belgin Petek Balci, Michael Barnett, Ann Bass, Veit U Becker, Mihaela Bejinariu, Florian Then Bergh, Arnfin Bergmann, Evanthia Bernitsas, Achim Berthele, Virender Bhan, Felix Bischof, Randall John Bjork, Gregg Blevins, Matthias Boehringer, Thomas Boerner, Robert Bonek, James D Bowen, Allen Bowling, Alexey N Boyko, Cavit Boz, Vera Bracknies, Stefan Braune, Vincenzo Brescia Morra, Bruno Brochet, Waldemar Brola, Paul Kenneth Brownstone, Miroslav Brozman, Donald Brunet, Ioan Buraga, Margaret Burnett, Mathias Buttmann, Helmut Butzkueven, Jonathan Cahill, Jonathan C Calkwood, William Camu, Mark Cascione, Giovani Castelnovo, Diego Centonze, Joao Cerqueira, Andrew Chan, Andrea Cimprichova, Stanley Cohan, Giancarlo Comi, Jill Conway, Joanna A Cooper, John Corboy, Jorge Correale, Brian Costell, David A Cottrell, Patricia K Coyle, Matthew Craner, Liying Cui, Luis Cunha, Anna Czlonkowska, Ana Martins da Silva, Joao de Sa, Jérôme de Seze, Marc Debouverie, Jan Debruyne, Danny Decoo, Gilles Defer, Tobias Derfuss, Norma H Deri, Bhupesh Dihenia, Peter Dioszeghy, Vladimir Donath, Benedicte Dubois, Martin Duddy, Pierre Duquette, Gilles Edan, Husnu Efendi, Stanton Elias, Peter J Emrich, Bonaventura Casanova Estruch, Evgeniy P Evdoshenko, Juergen Faiss, Alexander S Fedyanin, Wolfgang Feneberg, Jiske Fermont, Oscar Fernandez Fernandez, Francisco Coret Ferrer, Katharina Fink, Helen Ford, Corey Ford, Ada Francia, Mark Freedman, Benjamin Frishberg, Simonetta Galgani, George P Garmany, Klaus Gehring, Jeffrey Gitt, Claudio Gobbi, Lawrence P Goldstick, Rafael Arroyo Gonzalez, Francois Grandmaison, Nikolaos Grigoriadis, Olga Grigorova, Luigi Maria Edoardo Grimaldi, Jeffrey Gross, Katrin Gross-Paju, Mark Gudesblatt, Daniel Guillaume, Judith Haas, Viera Hancinova, Anca Hancu, Orla Hardiman, Arndt Harmjanz, Fedor R Heidenreich, G J D Hengstman, Joseph Herbert, Mark Herring, Suzanne Hodgkinson, Olaf M Hoffmann, Werner E Hofmann, William D Honeycutt, Le Hanh Hua, Dehui Huang, Yining Huang, DeRen Huang, Raymond Hupperts, Piroska Imre, Alan Keith Jacobs, Gabor Jakab, Elzbieta Jasinska, Kenichi Kaida, Jolanta Kalnina, Ara Kaprelyan, Guntis Karelis, Dimitrios Karussis, Amos Katz, Farit A Khabirov, Bhupendra Khatri, Takashi Kimura, Ilya Kister, Rasa Kizlaitiene, Eleonora Klimova, Juergen Koehler, Aparna Komatineni, Anselm Kornhuber, Krisztina Kovacs, Agnes Koves, Wojciech Kozubski, Georgi Krastev, Lauren B Krupp, Egon Kurca, Christoph Lassek, Guy Laureys, Liesly Lee, Eckart Lensch, Fritz Leutmezer, Hongzeng Li, Ralf A Linker, Michael Linnebank, Petra Liskova, Cristina Llanera, Jiahong Lu, Andreas Lutterotti, Jan Lycke, Richard Macdonell, Maciej Maciejowski, Mathias Maeurer, Rim V Magzhanov, Eva-Maria Maida, Lina Malciene, Yang Mao-Draayer, Girolama Alessandra Marfia, Clyde Markowitz, Vasileios Mastorodimos, Klotild Matyas, Jose Meca-Lallana, Juan Antonio Garcia Merino, Ioan Gheorghe Mihetiu, Ivan Milanov, Aaron E Miller, Andrejs Millers, Massimiliano Mirabella, Masanori Mizuno, Xavier Montalban, Lilina Montoya, Masahiro Mori, Stefanie Mueller, Jin Nakahara, Yuji Nakatsuji, Scott Newsome, Richard Nicholas, A Scott Nielsen, Esmaeil Nikfekr, Ugo Nocentini, Chiyoko Nohara, Kyoichi Nomura, Miroslav M Odinak, Tomas Olsson, B W van Oosten, Celia Oreja-Guevara, Patrick Oschmann, James Overell, Andrew Pachner, Gyula Panczel, Massimo Pandolfo, Caroline Papeix, Liliana Patrucco, Jean Pelletier, Raul Piedrabuena, Misha Pless, Udo Polzer, Krisztian Pozsegovits, Daiva Rastenyte, Sebastian Rauer, Gerd Reifschneider, Roberto Rey, Syed A Rizvi, Derrick Robertson, Jose Martinez Rodriguez, David Rog, Homayoun Roshanisefat, Vernon Rowe, Csilla Rozsa, Susan Rubin, Stanislaw Rusek, Francesco Saccà, Takahiko Saida, Antonio Vasco Salgado, Victoria Eugenia Fernandez Sanchez, Kalina Sanders, Maria Satori, Denis V Sazonov, Elio Angelo Scarpini, Eugen Schlegel, Myriam Schluep, Stephan Schmidt, Erich Scholz, H M Schrijver, Matthias Schwab, Raymond Schwartz, James Scott, Krzysztof Selmaj, Stuart Shafer, Basil Sharrack, Ivan A Shchukin, Yuko Shimizu, Penko Shotekov, Arno Siever, Karl-Otto Sigel, Scott Silliman, Magdolna Simo, Mihaela Simu, Vladimiro Sinay, Antonio Escartin Siquier, Aksel Siva, Ondrej Skoda, Andrew Solomon, Martin Stangel, Dusan Stefoski, Brian Steingo, Igor D Stolyarov, Pavel Stourac, Katrin Strassburger-Krogias, Erik Strauss, Olaf Stuve, Ivaylo Tarnev, Antonios Tavernarakis, Cristina Ramo Tello, Murat Terzi, Veronika Ticha, Marina Ticmeanu, Klaus Tiel-Wilck, Toomas Toomsoo, Niall Tubridy, Mark J Tullman, Hayrettin Tumani, Peter Turcani, Ben Turner, Antonio Uccelli, Francisco Javier Olascoaga Urtaza, Marta Vachova, Attila Valikovics, Silke Walter, Bart Van Wijmeersch, Ludo Vanopdenbosch, Joerg R Weber, Sara Weiss, Robert Weissert, Timothy West, Heinz Wiendl, Sandrine Wiertlewski, Brigitte Wildemann, Barbara Willekens, L H Visser, Galina Vorobeychik, Xianhao Xu, Takashi Yamamura, Yi N Yang, Sergio Martinez Yelamos, Michael Yeung, Alan Zacharias, Marvin Zelkowitz, Uwe Zettl, Meini Zhang, Hongyu Zhou, Ulf Zieman, Tjalf Ziemssen, Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel, Basel, Center for Neuroinflammation and Neurotherapeutics, and Multiple Sclerosis Division, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, Mellen Centre for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Montreal Neurological Institute, McGill University, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, Novartis Pharma AG, Lycalis, Brussels, AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Vermersch, Patrick, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, Dahlke, Frank, Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthia, Boerner, Thoma, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathia, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Lui, Czlonkowska, Anna, da Silva, Ana Martin, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gille, Derfuss, Tobia, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gille, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klau, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francoi, Grigoriadis, Nikolao, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, Deren, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Gunti, Karussis, Dimitrio, Katz, Amo, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agne, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andrea, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathia, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileio, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrej, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Toma, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, Jame, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthia, Schwartz, Raymond, Scott, Jame, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonio, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klau, Toomsoo, Tooma, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, and EXPAND Clinical Investigators
- Subjects
Adult ,Male ,0301 basic medicine ,Relative risk reduction ,medicine.medical_specialty ,Adolescent ,Placebo ,law.invention ,Cohort Studies ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Multiple Sclerosis, Chronic Progressive / drug therapy ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Benzyl Compounds ,Clinical endpoint ,Humans ,Medicine ,ComputingMilieux_MISCELLANEOUS ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,Expanded Disability Status Scale ,Dose-Response Relationship, Drug ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,Fingolimod ,Treatment Outcome ,Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITÀ MOTORIE ,030104 developmental biology ,Siponimod ,chemistry ,Disease Progression ,Azetidines ,Female ,Settore MED/26 - Neurologia ,Human medicine ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.
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- 2018
11. Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study.
- Author
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Kira JI, Nakahara J, Sazonov DV, Kurosawa T, Tsumiyama I, Willi R, Zalesak M, Pingili R, Häring DA, Ramanathan K, Kieseier BC, Merschhemke M, Su W, and Saida T
- Subjects
- Antibodies, Monoclonal, Humanized adverse effects, Double-Blind Method, Humans, Japan, Recurrence, Treatment Outcome, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting pathology
- Abstract
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home., Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia., Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks., Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported., Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.
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- 2022
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12. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.
- Author
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Bar-Or A, Wiendl H, Montalban X, Alvarez E, Davydovskaya M, Delgado SR, Evdoshenko EP, Giedraitiene N, Gross-Paju K, Haldre S, Herrman CE, Izquierdo G, Karelis G, Leutmezer F, Mares M, Meca-Lallana JE, Mickeviciene D, Nicholas J, Robertson DS, Sazonov DV, Sharlin K, Sundaram B, Totolyan N, Vachova M, Valis M, Bagger M, Häring DA, Ludwig I, Willi R, Zalesak M, Su W, Merschhemke M, and Fox EJ
- Subjects
- Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized adverse effects, Humans, Injections, Subcutaneous, Multiple Sclerosis chemically induced
- Abstract
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS)., Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion., Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC
τ ) and maximum plasma concentration ( Cmax ) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed., Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ , 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax , 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated., Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.- Published
- 2022
- Full Text
- View/download PDF
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