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1. The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021

Author

Dominika Stastna, Jiri Drahota, Michal Lauer, Aneta Mazouchova, Ingrid Menkyova, Jana Adamkova, Radek Ampapa, Michal Dufek, Marketa Grunermelova, Pavel Hradilek, Eva Kubala Havrdova, Jan Mares, Alena Martinkova, Zbysek Pavelek, Marek Peterka, Eva Recmanova, Petra Rockova, Ivana Stetkarova, Pavel Stourac, Marta Vachova, and Dana Horakova

Subjects
multiple sclerosis, disease-modifying therapy, high-efficacy therapy, platform therapy, treatment initiation, real-world data, registry, epidemiology, Medicine
Abstract

Aims. Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). Methods. First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. Results. Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. Conclusion. Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

Published
2024
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2. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials

Author

Carra, Adriana Josefa, Deri, Norma Haydee, Jose, Jorge Gustavo, del Valle Liwacki, Susana, Mainella, Carolina Natalia, Pagani, Fatima, Povedano, Guillermo, Alfici, Alberto Rodriguez, Tavolini, Dario Raul, Buonanotte, Carlos Federico, Burgos, Marcos, Giugni, Juan Carlos, Artesi, Juan Jose Martin, Rojas, Juan Ignacio, Zuin, Daniel Raul, Videla, Hugo Osvaldo, Correale, Jorge Daniel, Luetic, Geraldine G., Hodgkinson, Suzanne, Lechner-Scott, Jeannette, Parratt, John, Saines, Noel, Reddel, Stephen, Wijeratne, Tissa, Taylor, Bruce, Deisenhammer, Florian, Traxler, Gerhard, Leutmezer, Fritz, Wipfler, Peter, Weber, Joerg R., Lampl, Christian, Bartholome, Emmanuel, Dive, Dominique, Glibert, Nele, Perrotta, Gaetano, Pesch, Vincent, Buyle, Maarten, Wijmeersch, Bart, Willekens, Barbara, Basagic, Edin, Mehmedika Suljic, Enra, Klupka-Sarić, Inge, Danovska, Maya, Dimitrova, Maria, Genov, Krasimir, Izmaylov, Alim, Mavrov, Radoslav, Milanov, Ivan, Naydenov, Valcho, Shotekov, Penko, Tarnev, Ivaylo, Traykov, Latchezar, Emond, Francois, Selchen, Daniel, Rivest, Donald, Sabella, Lisa, Witkowski, Ludivine, Saveriano, Alexander, Bolano Solano, Addinson Rene, Ruiz, Cesar Augusto Franco, Nassar Tobon, Andrea Catalina, Cardozo, Carlos Alberto Navas, Schlesenger, Antonio, Triana, Javier Dario, Sarabia, Osvaldo Elias Lara, Montero, Luis Alfonso Zarco, Arango, Jorge Andres Jimenez, Basic, Silvio, Pasic, Marija Bosnjak, Soldo, Silva Butkovic, Habek, Mario, Kidjemet-Piskac, Spomenka, Matijaca, Meri, Vuletic, Vladimira, Ampapa, Radek, Dufek, Michal, Grunermelova, Marketa, Mares, Jan, Martinkova, Alena, Peterka, Marek, Stetkarova, Ivana, Stourac, Pavel, Talab, Radomir, Tyblova, Michaela, Marta, Vachova, Valis, Martin, Hradilek, Pavel, Rockova, Petra, Gross-Paju, Katrin, Haldre, Sulev, Airas, Laura, Karppa, Mikko, Bourre, Bertrand, Casez, Olivier, Ciron, Jonathan, Kwitakowski, Arnaud, Labauge, Pierre, Lebrun Frenay, Christine, Michel, Laure, Derache, Nathalie, Vukusic, Sandra, Laplaud, David-Axel, Beridze, Maia, Chakhava, George, Gauarashvili, Ann, Giorgadze, Gvantsa, Guldedava, Nana, Janelidze, Marina, Kiziria, Marina, Shakarishvili, Roman, Tsiskaridze, Alexander, Chkhikvishvili, Shalva, Albert, Christian, Berthele, Achim, Yalachkov, Yavor, Pitarokoili, Kalliopi, Kallmann, Boris-Alexander, Klotz, Luisa, Oschmann, Patrick, Pul, Refik, Rau, Daniela, Skripuletz, Thomas, Chan, Koon Ho, Lau, Alexander Yuk Lun, Li, Jessica Tsz Ching, Wong, Wa Tai, Maria, Biro Zita, Bokor, Magdolna, Dobos, Eniko, Janszky, Jozsef, Kovacs, Krisztina, Lazarcsik, Ildiko, Piros, Palma, Rozsa, Csilla, Satori, Maria, Simo, Magdolna, Nagy, Ferenc, Behari, Madhuri, Kulkarni, Rahul, Kumar, Radhakrishanan Suresh, Dwivedee, Shamsher, Iype, Thomas, Baviskar, Rahul, Mathukumalli, Neeharika L., Gilad, Ronit, Karussis, Dimitrios, Milo, Ron, Shahien, Radi, Vaknin, Adi, Weller, Boaz, Wilf-Yarkoni, Adi, Achiron, Anat, Aguglia, Umberto, Di Gregorio, Maria, Calabrese, Massimiliano, Cordioli, Cinzia, Sessa, Edoardo, Tomassini, Valentina, Inglese, Matilde, Castro Farfan, Freddy Guillermo, Roldan, Giovana Femat, Gonzalez Guardado, Antonio, Lopez Meza, Elmer, Maldonado, Jair Fernando, Boschetti, Laura Ordonez, Partida Medina, Luis Roberto, Frequin, Stephan, Hupperts, Raymond, Schrijver, Hans, Smolders, Joost, Diaz, Cesar Abel Castaneda, Pretell, Edwin, Boczarska-Jedynak, Magdalena, Bonek, Robert, Brola, Waldemar, Darda-Ledzion, Lidia, Fryze, Waldemar, Maciejowski, Maciej, Rejdak, Konrad, Rosciszewska-Zukowska, Iwona, Selmaj, Krzysztof, Szymanska, Malgorzata, Zajda, Małgorzata, Zielinski, Tomasz, Beata, Zakrzewska-Pniewska, Adam, Stepien, Swiat, Maciej, Kim, Byoung Joon, Kim, Ho-Jin, Kim, Kwang-Kuk, Shin, Ha Young, Kim, Sung Min, Kim, Woojun, Oh, Jeeyoung, Bakhtiyarova, Klara Z., Belova, Anna N., Davydovskaya, Maria V., Dudin, Viacheslav A., Erina, Olesya V., Evdoshenko, Evgeny P., Greshnova, Irina V., Khabirov, Farit A., Kotov, Sergey V., Makarov, Nikolay S., Maslova, Natalia, Mishin, Gennadiy N., Pokhabov, Dmitry V., Smagina, Inna V., Spirin, Nikolay N., Trushnikova, Tatiana N., Volkova, Larisa I., Zaslavskiy, Leonid G., Zhukova, Natalia G., Ceranic, Mirjana, Cvijanovic, Vera, Drulovic, Jelena, Gavric Kezic, Mira, Jovanovic, Dragoslava, Milicevic, Svetlana K., Raicevic, Ranko, Suknjaja, Vesna, Boskovic Matic, Tatjana, Vojinovic, Slobodan, Ruiz, Luis Brieva, Castillo Trivino, Tamara, Costa-Frossard Franca, Lucienne, Eichau Madueno, Sara, Forero Diaz, Lucia, Martinez, Jose Enrique, Martinez Yelamos, Sergio, Meca Lallana, Virginia, Oreja Guevara, Celia, Ramio i Torrenta, Lluis, Arroyo Gonzalez, Rafael, Guo, Yuh-Cherng, Ro, Long-Sun, Tsai, Nai-Wen, Wang, Kai-Chen, Yang, Fu-Chi, Cherkez, Alla, Deineka, Natalia, Delva, Mykhaylo, Goloborodko, Alla, Hovbakh, Iryna, Khavunka, Marta, Kmyta, Oleksii, Kozyolkin, Olexandr, Lekomtseva, Yevgeniya, Litovchenko, Tetyana, Moskovko, Sergii, Pashkovskyy, Valeriy, Riabichenko, Tetiana, Tovazhnyanska, Olena, Voloshyna, Nataliya, Hrebeniuk, Hanna, Sokolova, Larysa, Arun, Tarunya, Constantinescu, Cris, Harrower, Timothy, Mattoscio, Miriam, Paling, David, Pearson, Owen, Robertson, Neil, Webb, Stewart, Cottrell, David, Nicholas, Richard, Duddy, Martin, Anadani, Nidhiben, Belkin, Martin, Bernitsas, Evanthia, Borazanci, Aimee, Clark, David, Costell, Brian, Delgado, Silvia, Fox, Edward, Gudesblatt, Mark, Gupta, Vipan, Harel, Asaff, Harrison, Daniel, Herrman, Craig, Honeycutt, William David, Hua, Le, Hunter, Samuel, Katsamakis, George, Kilgo, William, Koffman, Boyd, Lindsey, William, Lynch, Sharon G., Mateen, Farrah J., McAllister, Peter, Farahmand, Arya, Morales, Idanis Berrios, Rahmlow, Megan, Naismith, Robert, Napoli, Salvatore, Newman, Stephen, Pardo, Gabriel, Patel, Nirav, Scott, James, Purino, Lorraine, Vasquez, Alberto B., Weisman, David, Wray, Sibyl, Wynn, Daniel, Dihenia, Bhupesh, Obeidat, Ahmed, Ayala, Ricardo, Erwin, April, Betz, Michelle, DeAngelis, Teresa, Osborne Dusan Stefoski, Benjamin, Giang, Daniel, Hendin, Barry, Nagaraj, Arun, Saltis, Lawrence, Singer, Barry, Balabanov, Roumen, Bromley, Steven Michael, Puente, John, Tran, Duc, Kojan, Suleiman, Graves, Jennifer, Fishman, Simon, Maher, Leo, Londono, Diana, Sadiq, Mohamed, Alekseenko, Yuri, Fedulau, Aliaksandr, Kulesh, Sergey, Mikhailova, Elena, Navumava, Halina, Aragon deVecino, Maria Cecilia, Callegaro, Dagoberto, Daccach Marques, Vanessa, Finkelsztejn, Alessandro, Guerreiro, Alexandre, Kleinpaul, Rodrigo, Koiti Sato, Henry, Luiz Longo, Alexandre, Papais Alvarenga, Regina Maria, Pereira Damasceno, Benito, Pereira Gomes Neto, Antonio, Diniz Carneiro, Denise S., Tauil, Carlos Bernardo, Maciel Dias, Ronaldo, Olival, Guilherme, Zago Melo Dias, Paula, de Jesus Carvalho, Margarete, Sato, Douglas Kazutoshi, Forcelini, Cassiano Mateus, Pelov, Plamen, Haralanov, Lyubomir, Ikonomov, Rosen, Ivanov, Ivan, Kastrev, Sasho, Kirilov, Krasimir, Lilovski, Hristo, Maslarov, Dimitar, Staikov, Ivan, Zhelyazkov, Petko, Freedman, Mark, MacLean, Gregg, Marriott, James, McKelvey, John Roger, Girard, Jean-Marc, Vorobeychik, Galina, Morrow, Sarah, Clavelou, Pierre, de Seze, Jerome, Louapre, Celine, Maurousset, Aude, Ruet, Aurelie, Thouvenot, Eric, Morel, Nathalie, Montcuquet, Alexis, Rouhart, Francois, Angstwurm, Klemens, Bayas, Antonios, Bittner, Stefan, Heesen, Christoph, Kowarik, Markus, Marckmann-Boenke, Silke, Muller, Thomas, Zimmermann, Julian, Nelles, Gereon, Paul, Friedemann, Then Bergh, Florian, Wildemann, Brigitte, Zettl, Uwe Klaus, Ziemssen, Tjalf, Doerr, Jan-Marcus, Chroni, Elisabeth, Dardiotis, Efthymios, Doskas, Triantafyllos, Gatzonis, Stylianos, Grigoriadis, Nikolaos, Karageorgiou, Klimentini, Kouremenos, Evangelos, Mitsias, Panayiotis, Spengos, Konstantinos, Kimiskidis, Vasilios, Evangelopoulos, Maria E., Fakas, Nikolaos, Karanasios, Panagiotis, Kyritsis, Athanasios, Maltezou, Maria, Sotirli, Stefania, Tsolaki, Magda, Rohtagi, Anshu, Mukherjee, Joy, Nellikunja, Shankara, Srinivasa, Rangashetty, Sharma, Arvind, Chowdhury, Debashish, Kalita, Jayantee, Brescia Morra, Vincenzo, Centonze, Diego, Gasperini, Claudio, Grimaldi, Luigi, Maniscalco, Giorgia Teresa, Patti, Francesco, Salemi, Giuseppe, Trojano, Maria, Amato, Maria Pia, Malucchi, Simona, Brambilla, Laura, Pozzilli, Carlo, Al Roughani, Raed, Karelis, Guntis, Kalnina, Jolanta, Millers, Andrejs, Mickeviciene, Dalia, Giedraitiene, Natasa, Kazlauskas, Andrius, Malciene, Lina, Joseph, Joyce Pauline, Chung, Law Wan, Looi, Irene, Remli, Rabani, Binti Sapuan, Sapiah, Abdullah, Suhailah, Carbajal Ramirez, Angelica, Espino Ojeda, Alba, Silvestre Bejar Medina, Jesus, Quinones Aguilar, Sandra, Rivas Alonso, Veronica, de la Rosa, Rogelio Francisco, San Juan Orta, Daniel, Misic, Octavian, Odainic, Olesea, Torkildsen, Oivind, Schuler, Stephan, Broch, Line, Canete, Ma. Teresa, Hiyadan, John Harold, Hormillosa, Mary Pauline, Rosales, Raymond L., Adamczyk Sowa, Monika, Bartosik-Psujek, Halina, Berkowicz, Tomasz, Czarnecki, Maciej, Kłodowska, Gabriela, Klosek, Agata, Koscielniak, Jozef, Lisewski, Pawel, Mielcarek, Bartlomiej, Piasecka-Stryczynska, Karolina, Potemkowski, Andrzej, Stasiołek, Mariusz, Krzystanek, Ewa, Lasek-Bal, Anetta, Sikorska, Swietlana, Szczudlik, Andrzej, Gospodarczyk-Szot, Krystyna, Wierzchowska-Cioch, Ewa, K. Jastrzebska, Iwona, Capela, Carlos, Cerqueira, Joao, Correia, Ana Sofia, Correia, Filipe, Ferreira, Joaquim J., Gouveia, Raquel, Mendes, Irene, Nunes, Carla Cecilia, Timoteo, Angela, Veira, Carlos, Martins da Silva, Ana, Domingues, Joana, Chinea, Angel R, Tiu, Cristina, Balasa, Rodica, Chiru, Mirela, Dulamea, Adriana Octaviana, Silviu Manescu, Emilian, Mitrea, Dan, Mitu, Cristina, Nicolae, Silvia Maria, Filip, Carmen Corina Roman, Sabau, Monica, Vanghelie, Doinita, Varga, Ioana, Nunkoo, Vharoon, Agafina, Alina S., Gennadevna, Arefeva Elena, Alexeeva, Tatiana M., Bogdanov, Enver, Dorogov, Nikolay, Doronina, Olga, Goncharova, Zoya, Khasanova, Dina, Korobko, Denis, Pankratov, Evgeny V., Parshina, Elena, Poverennova, Irina, Prokopenko, Semyion V., Sazonov, Denis V., Shkilnyuk, Galina, Sivertseva, Stella, Stolyarov, Igor, Totolyan, Natalia A., Tsukurova, Larisa A., Vorobyeva, Olga V., Voznyuk, Igor A., Zakharova, Maria, Ardashev, Igor V., Boyko, Alexey, Alshehri, Ebtesam, Alkhawajah, Nuha M, Alfugham, Nora, Quek, Amy, Kevin, Tan, Dupejova, Beata, Feketova, Sona, Hancinova, Viera, Jurcaga, Frantisek, Turcani, Peter, Krastev, Georgi, Cimprichova, Andrea, Perichtova, Magdalena, Hojs-Fabjan, Tanja, Horvat Ledinek, Alenka, Savsek, Lina, Bateman, Kathleen, Frost, Andrew Charles, Henning, Franclo, Retief, Chris Francois, Aguado Valcarcel, Marta, Morales, Eduardo Aguera, Alonso Torres, Ana Maria, Borrega Canelo, Laura, Casanova Estruch, Bonaventura, Gascon Gimenez, Francisco, Ayuso, Guillermo I, Martinez Gines, Maria Luisa, Eustasio Meca Lallana, Jose, Rodriguez Antiguedad, Alfredo, Blasco Quilez, Rosario, Brieva Ruiz, Luis, Piehl, Fredrik, Lycke, Jan, Katsarogiannis, Evangelos, Nilsson, Christer, Hoepner, Robert, Zecca, Chiara, Findling, Oliver, Asawavichienjinda, Thanin, Kasemsap, Narongrit, Prayoonwiwat, Naraporn, Mhiri, Chokri, Ağan Yıldırım, Kadriye, Boz, Cavit, Efendi, Husnu, Soysal, Aysun, Terzi, Murat, Uygunoglu, Ugur, Gümüş, Haluk, Mungan, Semra, Ozakbas, Serkan, Serhan Sevim, Mustafa, Tamam, Yusuf, Kale, Nilufer, Karabudak, Rana, Bachinskaya, Natalia, Buchakchyiska, Nataliia, Chmyr, Galyna, Dzyak, Ludmyla, Ivashchenko, Svitlana, Kalbus, Oleksandr, Kareta, Serhiy, Korolova, Oksana, Kostiuchenko, Andrii, Kruchkevych, Zhanna, Larysa, Kadina, Mishchenko, Tamara, Moroz, Olena, Neryanova, Yuliya, Pasiura, Ihor, Pohrebnyak, Oleksandr, Pryshchepa, Volodymyr, Sanotskyy, Yanosh, Shkrobot, Svitlana, Shulga, Olga, Smolanka, Volodymyr, Tomakh, Nataliya, Zhuravlyova, Natalia, Allen, Alison B., Armstrong, Robert, Antezana, Ariel, Baker, Matthew, Bass, Ann, Benenati, Diana, Benson, Dalton, Beretich, Biljana, Burke, Deborah, Calkwood, Jonathan, Carpenter, Adam, Drake, Ryan, Dujmovic Basuroski, Irena, Gupta, Ajay, Hentati, Afif, Kaplan, Jeffrey, Katsafanas, Constance, Keegan, Andrew, Khatri, Bhupendra, Luzzio, Christopher, Malik, Maheen, Bennette, Myers, Miravalle, Augusto, Montoya, Liliana, Nash, Marshall, Poole Pharr, Emily, Sater, Richard A., Scagnelli, John, Schulman, Alan, Shafer, Stuart, Stein, Lee, Vandersluis, Joel, Williams, Armistead, Winkley, James, Berkovich, Regina, Cerghet, Mirela, Horton, Lindsay, Jacobs, Daniel H., Laurin, Nida, Liow, Kore, Robertson, Derrick, Mattson, David, Cabrera, Alicia V., Leist, Thomas, Negroski, Donald, Royter, Vladimir, LaGanke, Christopher, Winner, Paul, Sweeney, Michael, Weinberg, Lawrence A., Smith, Andrew, Rivas-Rodriguez, Erica, Wagner, Kimberly, Montalban, Xavier, Vermersch, Patrick, Arnold, Douglas L, Bar-Or, Amit, Cree, Bruce A C, Cross, Anne H, Kubala Havrdova, Eva, Kappos, Ludwig, Stuve, Olaf, Wiendl, Heinz, Wolinsky, Jerry S, Dahlke, Frank, Le Bolay, Claire, Shen Loo, Li, Gopalakrishnan, Sathej, Hyvert, Yann, Javor, Andrija, Guehring, Hans, Tenenbaum, Nadia, and Tomic, Davorka

Published
2024
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3. Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry

Author

Pavel Potuznik, Jiri Drahota, Dana Horakova, Marek Peterka, Aneta Mazouchova, David Matyas, Zbysek Pavelek, Marta Vachova, Eva Recmanova, Ivana Stetkarova, Jana Libertinova, Jan Mares, Pavel Stourac, Marketa Grunermelova, Alena Martinkova, Jana Adamkova, Pavel Hradilek, Radek Ampapa, Michal Dufek, Eva Kubala Havrdova, and Dominika Stastna

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). Objectives Provide experience with cladribine therapy in a real-world setting. Methods This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. Results In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. Conclusion This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.

Published
2024
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4. Daclizumab high-yield process in the treatment of relapsing–remitting multiple sclerosis

Author

Jana Lizrova Preiningerova and Marta Vachova

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Daclizumab is a humanized monoclonal antibody that binds to the α subunit (CD25) of the interleukin-2 receptor and favorably modulates the immune environment in multiple sclerosis (MS). Blockage of CD25, among other effects, causes expansion and enhanced function of regulatory CD56 bright natural killer cells, which seems to be the leading mechanism of action in MS. Phase II and III clinical trials have demonstrated that monthly subcutaneous injections of daclizumab high yield process (DAC HYP) 150 mg in patients with relapsing MS led to a significant reduction of annualized relapse rate and decreased number of contrast-enhanced lesions on brain magnetic resonance imaging. Treatment with DAC HYP had efficacy superior to treatment with weekly injections of interferon β1a. This review summarizes the development of and clinical experience with daclizumab in MS.

Published
2017
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5. To be or not to be vaccinated: The risk of MS or NMOSD relapse after COVID-19 vaccination and infection

Author

Dominika Stastna, Ingrid Menkyova, Jiri Drahota, Tereza Hrnciarova, Eva Kubala Havrdova, Marta Vachova, Michaela Andelova, Pavlina Kleinova, Ivana Kovarova, Eva Krasulova, Jana Lizrova Preiningerova, Iveta Novakova, Klara Novotna, Martina Novotna, Petra Nytrova, Jana Pavlickova, Barbora Srpova, Katerina Storey, Veronika Ticha, Michaela Tyblova, Tomas Uher, Karolina Vodehnalova, and Dana Horakova

Subjects
COVID-19 Vaccines, Multiple Sclerosis, Neurology, Recurrence, Neuromyelitis Optica, Vaccination, COVID-19, Humans, Neurology (clinical), General Medicine, BNT162 Vaccine, Czech Republic, Retrospective Studies
Abstract

COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors.Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made.We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS.There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.

Published
2022

6. Corrigendum to ’To be or not to be vaccinated: The risk of MS or NMOSD relapse after COVID-19 vaccination and infection’[Multiple sclerosis and related disorders vol. 65 (2022) 104014]

Author

Dominika Stastna, Ingrid Menkyova, Jiri Drahota, Tereza Hrnciarova, Eva Kubala Havrdova, Marta Vachova, Michaela Andelova, Pavlina Kleinova, Ivana Kovarova, Eva Krasulova, Jana Lizrova Preiningerova, Iveta Novakova, Klara Novotna, Martina Novotna, Petra Nytrova, Jana Pavlickova, Barbora Srpova, Katerina Storey, Veronika Ticha, Michaela Tyblova, Tomas Uher, Karolina Vodehnalova, and Dana Horakova

Subjects
Neurology, Neurology (clinical), General Medicine
Published
2023
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7. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author

Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, Stangel, Martin, Boehringer, Matthia, Martin Hoffmann, Olaf, Oschmann, Patrick, Hohlfeld, Reinhard, Walter, Silke, Menck, Sylvia, Sprenger, Till, Ziemssen, Tjalf, Ulrich Becker, Veit, Straeten, Vera, Kilidireas, Konstantino, Voumvourakis, Konstantino, Fakas, Nikolao, Grigoriadis, Nikolao, Koves, Agne, Rozsa, Csilla, Kovacs, Krisztina, Vecsei, Laszlo, Maria, Satori, Biro, Zita, Rohatgi, Anshu, Khurana, Dheeraj, Durai Pandian, Jeyaraj, Dev Mukherji, Joy, Pandit, Lekha, Angamuthu Kanikannan, Meena, Ghosh, Pahari, Chakor, Rahul, Kulkarni, Rahul, Gursahani, Roopkumar, Ravat, Sangeeta, Rangasetty, Srinivasa, Kumar, Suresh, Shifrin, Alla, Karni, Arnon, Shahien, Radi, Milo, Ron, Uccelli, Antonio, Pozzilli, Carlo, Sacca, Francesco, Lus, Giacomo, Alessandra Marfia, Girolama, Brambilla, Laura, Salvetti, Marco, Filippi, Massimo, Zaffaroni, Mauro, Gallo, Paolo, Rossi, Silvia, Bonavita, Simona, Studer, Valeria, Millers, Andrej, Karelis, Gunti, Kalnina, Jolanta, Mickeviciene, Dalia, Kizlaitiene, Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Published
2020
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8. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY)

Author

Diego Cadavid, Michelle Mellion, Raymond Hupperts, Keith R Edwards, Peter A Calabresi, Jelena Drulović, Gavin Giovannoni, Hans-Peter Hartung, Douglas L Arnold, Elizabeth Fisher, Richard Rudick, Sha Mi, Yi Chai, Jie Li, Yiwei Zhang, Wenting Cheng, Lei Xu, Bing Zhu, Susan M Green, Ih Chang, Aaron Deykin, Sarah I Sheikh, Eduardo Agüera Morales, Abdullatif Al Khedr, Radek Ampapa, Rafael Arroyo, Martin Belkin, Robert Bonek, Alexey Boyko, Ruggero Capra, Diego Centonze, Pierre Clavelou, Marc Debouverie, Jelena Drulovic, Keith Edwards, Nikos Evangelou, Evgeniy Evdoshenko, Oscar Fernández, Victoria Fernández Sánchez, Mark Freedman, Steven Freedman, Waldemar Fryze, Antonio Garcia-Merino, Mira Gavric-Kezic, Angel Ghezzi, Olivier Gout, Luigi Grimaldi, Barry Hendin, Hanka Hertmanowska, Rogier Hintzen, Pavel Hradilek, Jan Ilkowski, Evelina Ivashinenkova, Guillermo Izquierdo, Francois Jacques, Gabor Jakab, Farit Khabirov, Gabriela Klodowska-Duda, Samuel Komoly, Smiljana Kostic, Ivana Kovarova, Marcelo Kremenchuzky, Christopher Laganke, Yves LaPierre, Maciej Maciejowski, Francois Grand Maison, Girolama Alessandra Marfia, Sergio Martínez Yélamos, Eva Meluzinova, Xavier Montalban, Ronald Murray, Robert Naismith, Scott Newsome, Viet Nguyen, Delia Oreja, Gabriel Pardo, Elena Pasechnik, Francesco Patti, Andrzej Potemkowski, Semen Prokopenko, Peiqing Qian, Alfredo Rodríguez-Antigüedad, Howard Rossman, Csilla Rozsa, Fernando Sánchez López, Krzysztof Selmaj, Eli Silber, Adam Stepien, Anna Stepniewska, Maciej Swiat, Gordana Toncev, Ayman Tourbah, Tatyana Trushnikova, Antonio Uccelli, Marta Vachova, Martin Valis, Laszlo Vecsei, Sandrine Wiertlewski, Mauro Zaffaroni, Tomasz Zielinski, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
0301 basic medicine, EXPRESSION, medicine.medical_specialty, Paced Auditory Serial Addition Test, Phases of clinical research, Placebo, Settore MED/26, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, SPINAL-CORD REMYELINATION, 10. No inequality, Adverse effect, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, CENTRAL-NERVOUS-SYSTEM, Oligodendrocyte differentiation, medicine.disease, 3. Good health, 030104 developmental biology, Neurology (clinical), CNS, business, OLIGODENDROCYTE DIFFERENTIATION, 030217 neurology & neurosurgery, LINGO-1
Abstract

Summary Background Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. Methods We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18–58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov , number NCT01864148 . Findings Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. Interpretation Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. Funding Biogen.

Published
2019
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9. Multiple sclerosis, neuromyelitis optica spectrum disorder and COVID-19: A pandemic year in the Czech Republic

Author

Ivana Stetkarova, Martin Vališ, Radek Ampapa, J. Adamkova, Marek Peterka, Ivana Woznicova, Ingrid Menkyova, Eva Recmanova, Dominika Stastna, Aneta Mazouchova, Petra Rockova, Markéta Grünermelová, Jiri Drahota, Dana Horakova, Matous Rous, and Marta Vachova

Subjects
medicine.medical_specialty, B-cell depleting therapies, Population, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Disease-modifying therapies, 030212 general & internal medicine, Original Research Article, education, Pandemics, Aged, Czech Republic, education.field_of_study, Neuromyelitis optica, SARS-CoV-2, business.industry, Mortality rate, Incidence (epidemiology), Neuromyelitis Optica, Infant, COVID-19, General Medicine, medicine.disease, Comorbidity, Pneumonia, Neuromyelitis optica spectrum disorder, Neurology, Cohort, Neurology (clinical), business, Body mass index, 030217 neurology & neurosurgery
Abstract

Background: When the novel coronavirus disease 2019 (COVID-19) appeared, concerns about its course in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) arose. This study aimed to evaluate the incidence, severity and risk factors of the more severe COVID-19 course among MS and NMOSD patients. Methods: From March 1, 2020, to February 28, 2021, 12 MS centres, representing 70% of the Czech MS and NMOSD population, reported laboratory-confirmed COVID-19 cases via the Czech nationwide register of MS and NMOSD patients (ReMuS). The main outcome was COVID-19 severity assessed on an 8-point scale with a cut-off at 4 (radiologically confirmed pneumonia) according to the World Health Organisation´s (WHO) COVID-19 severity assessment. Results: We identified 958 MS and 13 NMOSD patients, 50 MS and 4 NMOSD patients had pneumonia, 3 MS and 2 NMOSD patients died. The incidence of COVID-19 among patients with MS seems to be similar to the general Czech population. A multivariate logistic regression determined that higher body mass index (BMI [OR 1.07, 95% CI, 1.00-1.14]), older age (OR per 10 years 2.01, 95% CI, 1.41-2.91), high-dose glucocorticoid treatment during the 2 months before COVID-19 onset (OR 2.83, 95% CI, 0.10-7.48) and anti-CD20 therapy (OR 7.04, 95% CI, 3.10-15.87) were independent variables associated with pneumonia in MS patients. Increase odds of pneumonia in anti-CD20 treated MS patients compared to patients with other disease-modifying therapy (same age, sex, BMI, high-dose glucocorticoid treatment during the 2 months before COVID-19 onset, presence of pulmonary comorbidity) were confirmed by propensity score matching (OR 8.90, 95% CI, 3.04-33.24). Reports on COVID-19 infection in patients with NMOSD are scarce, however, data available up to now suggest a high risk of a more severe COVID-19 course as well as a higher mortality rate among NMOSD patients. In our cohort, 4 NMOSD patients (30.77%) had the more severe COVID-19 course and 2 patients (15.39%) died. Conclusion: The majority of MS patients had a mild COVID-19 course contrary to NMOSD patients, however, higher BMI and age, anti-CD20 therapy and high-dose glucocorticoid treatment during the 2 months before COVID-19 onset were associated with pneumonia. Based on this study, we have already started an early administration of anti-SARS-CoV-2 monoclonal antibodies and preferential vaccination in the risk group of patients., Graphical abstract Image, graphical abstract

Published
2021

10. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

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.

Published
2018
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11. Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2) : a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Jennifer Graves, Adrian Pace, Maria Pia Sormani, Devon S. Conway, Bianca Weinstock-Guttman, Frederick E. Munschauer, Corey C. Ford, Vernon Rowe, Jana Lizrova Preiningerova, Shiv Saidha, Radek Ampapa, Jens Kuhle, Harold L. Moses, Claire S Riley, Tobias Derfuss, Lilyana Amezcua, Joshua Barton, Kottil Rammohan, Pierre Duquette, Thomas Leist, Alexander Rae-Grant, Evanthia Bernitsas, Myla D. Goldman, R. Talab, Jerry S. Wolinsky, Nina De Klippel, Guillermo Izquierdo Ayuso, Bridget Bagert, Virginia Devonshire, Mariko Kita, Hayrettin Tumani, Bhatia Perminder, Scott D. Newsome, Paul S. Giacomini, Frédéric Sedel, Jan Lycke, M. S. Freedman, Stewart Webb, Sanjay Yathiraj, Agata Klosek, Stephen Krieger, Edward Fox, Malgorzata Zajda, Eva Meluzinova, Valerie J Block, Lluís Ramió-Torrentà, John R. Corboy, Aaron E. Miller, Xavier Montalban, Mark A. Agius, Michelle L Apperson, Patricia K. Coyle, Giancarlo Comi, Jose Enrique Martinez Rodriguez, Daniela Rau, Derrick Robertson, Elias Hamp Birte, Douglas L. Arnold, Fred D. Lublin, Galina Vorobeychik, Benjamin Greenberg, Mathias Buttmann, Daniel Bandari, Ludivine Witkowski, Sharon G. Lynch, Victoria Fernandez Sanchez, Jonathan Calkwood, Maria Satori, Tania Kuempfel, Rana K. Zabad, J. Marc Girard, Bruce A.C. Cree, Ahmed T. Toosy, Don J. Mahad, Bruce A. Cohen, Jozef Koscielniak, Jonathan Carter, Daniel Selchen, Paul Friedemann, Sharon Stoll, Fryze Waldemar, Gerd Reifschneider, Mark S. Freedman, Gary Cutter, Franz Fazekas, Robert T. Naismith, Marta Vachova, Richard MacDonell, Mary Ann Picone, Gavin Giovannoni, Randall Trudell, Barbara Willekens, Orhan Aktas, Mark Marriott, Roger McKelvey, Bruce C.A. Cree, Christopher Severson, Rafael Arroyo Gonzalez, Kyle Smoot, Murat Terzi, Joanna Cooper, Lou Brundin, Hans-Peter Hartung, Piotr Sokolowski, Joe Guadagno, Stephen C. Reingold, Klaus Schmierer, Guy Laureys, Robert P. Lisak, Lawrence Samkoff, Carlo Pozzilli, Celia Oreja Guevara, Mitchel Freedman, Anthony T. Reder, and SPI2 investigative teams

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Biotin, Placebo, Severity of Illness Index, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Outcome Assessment, Health Care, Severity of illness, Aged, Disease Progression, Female, Humans, Middle Aged, Multiple Sclerosis, Chronic Progressive, Vitamin B Complex, Walking Speed, Clinical endpoint, Medicine, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Clinical trial, 030104 developmental biology, Cohort, Neurology (clinical), Human medicine, business, 030217 neurology & neurosurgery
Abstract

Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18-65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5-6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15-27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81-2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (

Published
2020

12. Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting

Author

Maria Trojano, Helmut Butzkueven, Ludwig Kappos, Heinz Wiendl, Tim Spelman, Fabio Pellegrini, Yi Chen, Qunming Dong, Harold Koendgen, Shibeshih Belachew, Jorge Correale, Alejandro Caride, Norma H. Deri, Carlos Ballario, Simon Broadley, Chris Kneebone, Michael Barnett, John Pollard, Suzanne Hodgkinson, Allan Kermode, Richard Macdonell, John King, Jeannette Lechner-Scott, Noel Saines, Mark Slee, Chris Plummer, Barbara Willekens, Ludo Vanopdenbosch, Rémy Phan-Ba, Valérie Delvaux, Veronique Bissay, Jan Debruyne, Danny Decoo, Roeland Crols, Anoek Symons, Guy Nagels, Vincent Van Pesch, Christian Sindic, Benedicte Dubois, Robert Medaer, Marie D'Hooghe, Daniel Guillaume, Eric De Smet, Pierrette Seeldrayers, Andreas Lysandropoulos, Mathieu Vokaer, Karine Geens, Christina Willems, Pierre Denayer, Michel Bureau, Cecile Retif, Michel Dupuis, Olivier Bouquiaux, Patrick Vanderdonckt, William van Landegem, Jo Caekebeke, Erwin Van Ingelghem, Katelijne Peeters, Pascale Gerard, Alain Maertens de Noordhout, Philippe Desfontaines, Etienne Urbain, Inge Declercq, Bart Van Wijmeersch, Erwin Vanroose, Alain Wibail, Emmanuel Barthomolé, Melanie Ursell, Margaret Elizabeth Sweet, David Howse, Draga Jichici, Melad Shawush, Mike Namaka, Anthony Traboulsee, Stan Hashimoto, Raymond Lo, Paul Marchetti, Yves Lapierre, Francois Jacques, Gregg MacLean, Virender Bhan, Pierre Duquette, Bradley Stewart, John Paulseth, Marcelo Kremenchutzky, Galina Vorobeychik, Paul O'Connor, François Grand'Maison, Eva Havrdova, Eva Meluzinová, Martin Valis, Radomír Talab, Pavel Stourac, Olga Zapletalová, Michal Dufek, Vladimíra Sládková, Alena Novotna, Romana Vancurová, Libuse Lhotaková, Jiri Fiedler, Marta Vachova, David Dolezil, Ivana Stetkarova, Adela Rehankova, Petr Psenica, Veronika Ulehlova, Sona Feketova, Ondrej Skoda, Markus Färkkilä, Sarasoja Taneli, Keijo Koivisto, Juha Matti Seppä, Laura Airas, Irina Elovaara, Päivi Hartikainen, Tuula Pirttila, Pierre Louchart, Olivier Ille, Jean philippe Thenint, Etienne Godet, Marcel Maillet Vioud, Renato Colamarino, Michel Gugenheim, Jerome Grimaud, Audrey Kopf, Christophe Billy, Bernard Huttin, Jean paul Borsotti, Philippe Devos, Jean bertin N Kendjuo, Albert Verier, Stephane Chapuis, Nathalie Daluzeau, Gilles Angibaud, Marie-Sylvie Artaud Uriot, François Ziegler, François Sellal, Antoine Moulignier, Isabelle Lavenu, Samir Ismail, Richard Devy, Manuel Suceveanu, Marc Wagner, Sebastien Marcel, Faycal Derouiche, Sohrab Mostoufizadehghalamfarsa, Sophie Delalande, Irene Ruggieri, Catherine Bossu Van Nieuwenhuyse, Chantal Nifle, Basile Ondze, Carmen Gurau Vasilescu, Cyrille Vongsouthi, Marc Coustans, Olivier Anne, Josephine Amevigbe, Jerome Servan, Marc Merienne, Philippe Eck, Stephane Berroir, Philippe Busson, Bruno Barroso, Jean-Marc Larrieu, Catherine Louvet Giendaj, Imad Malkoun, Patrick Hautecoeur, Arnaud Kwiatkowski, Andre Pouliquen, Guillaume Garrigues, Olivier Delerue, Pierric Giraud, Julien Gere, Jean Vaunaize, Olivier Dereeper, Nicolas Seiller, Roger Alsassa, Mihaela Vlaicu, Veronique Neuville, Jean Marc Faucheux, Patricia Bernady, Guy Fanjaud, François Viallet, Michael Schroeter, Sylke Schlemilch-Paschen, Thomas Lange, Kin-Arno Bohr, Klaus Jendroska, Elisabeth Rehkopf, Arnfin Bergmann, Christoph Kleinschnitz, Thomas Postert, Peter Scholz, Uwe Mauz, Hubert Stratmann, Veneta Siefjediers, Martin Prantl, Klaus Gehring, Ruth Zellner, Kathrin Junge, Anton Zellner, Valerina Bacay, Eugen Schlegel, Udo Polzer, Erik Strauss, Andreas Link, Christoph Stenzel, Matthias Freidel, Joachim Drews, Christian Neudert, Frank Schmitz, Joachim Jaeger, Said Masri, Wolfgang Heuberger, Beate Trausch, Oliver Ruhnke, Serena Scarel, Kathlen Bach, Michael Ernst, Harald Landefeld, Nils Richter, Stephan Schmidt, Michaela Krause, Alezander Dressel, Roland Ruth, Kerstin Anvari, Jens Gossling, Christoph Schenk, Oliver Tiedge, Lutz Bode, Hans-Thomas Eder, Oliver Pfeffer, Reinhard Krug, Christoph Lassek, Eberhard Fleischer, Sven Meuth, Luisa Hildegard Klotz, Ines Peglau, Borries Kukowski, Birgit Herting, Kersten Guthke, Jurgen Schierenbeck, Bernd Brockmeier, Holger Albrecht, Matthias Wuttke, Regine Augspach-Hofmann, Stefan Gunther, Martin Redbrake, Christian Franke, Klaus Buchner, Thomas Gratz, Rolf Horn, Frank Doemges, Martin Schreiber, Thomas Brosch, Markus Horn, Matthias Kittlitz, Gabriele Vulturius, Paul Hinse, Rolf Malessa, Stephan Wiehler, Zaza Katsarava, Oliver Kastrup, Ulrich Kausch, Martin Gullekes, Markus Fickinger, Wilhelm Wenzel, Ingolf C. Botefur, Gerd Reifschneider, Sebastian Rauer, Michael Lang, Lutz Harms, Ulrich Eckhardt, Simone Cursiefen, Ralf Linker, Klemens Angstwurm, Judith Haas, Ivo Schuetze, Eva Rohm, H. Stienker-Fisse, Michael Sailer, Johannes Bohringer, Mathias Maurer, Eberhard Bause, Ronald Wersching, Reinhardt Dachsel, Sylke Domke, Frank Hoffman, Bjorn Tackenberg, Kerstin Roch, Uwe Ziebold, Boris Kallmann, Bernhard Buehler, Judith Faiss, Juergen Faiss, Sebastian Schimrigk, Christian Menges, Karl Christian Knop, Wolfgang Koehler, Arno Siever, Johannes Bufler, Georg Gramsl, Benedicta Kuhnler, Matthias Maschke, Florian Stogbauer, Lisa Staude, Florian Bethke, Andreas Bitsch, Arndt D. Harmjanz, Jorg Windsheimer, Bernd C. Kieseier, Ralf Berkenfeld, Hayrettin Tumani, Michael Kirsch, Brigitte Wildemann, Regina Daniels, Klaus Gottwald, Wolfgang-Gerhard Elias, Olaf Hoffmann, Matthias Schwab, Christopher Pilz, Fabian Klostermann, Kerstin Hellwig, Achim Berthele, Antonios Bayas, Daniel Molitor, Christoph Grothe, Bert Wagner, Klimentini Karageorgiou, Dimosthenis Mitsikostas, Antonios Kodounis, Andreas Plaitakis, Alexandros Papadimitriou, Nikolaos Grigoriadis, Nikolaos Vlaikidis, Evaggelos Koutlas, Athanassios Kyritsis, Panagiotis Papathanassopoulos, Nikolaos Makris, Antonios Tavernarakis, Elio Scarpini, Enrico Montanari, Maria Giovanna Marrosu, Maria Pia Amato, Mariarosa Rottoli, Alessandra Lugaresi, Ciro Florio, Claudio Gasperini, Luigi Grimaldi, Enrico Millefiorini, Tatiana Koudriavtseva, Franco Perla, Renato Mantegazza, Antonio Bertolotto, Angelo Ghezzi, Sandra Quinones Aguilar, Eli Skromne Eisenberg, Leondardo Llamas Lopez, Rocio Marquez Estudillo, H.M. Schrijver, M.C. Wittebol, J.C. Baart, A.E.L. van Golde, G.J.D. Hengstman, P.H.M. Pop, M. Bos (Geldrop), R. Medaer, Angelique Schyns-Soeterboek, A. van der Zwart, A.J.H. van Diepen, G.A.M. Verheul, W.I.M. Verhagen, M. Bos (Helmond), R.J.G.M. Witjes, L.G.F. Sinnige, E.Th.L. van Munster, E.A.C.M. Sanders, Ron van Dijl, R.M.M. Hupperts, S.T.F.M. Frequin, L.H. Visser, J.M.L. Henselmans, J.W.B. Moll, Rune Midgard, Kjell Morten Myhr, Astrid Edland, Wenche Telstad, Tone Hognestad, Christian Lund, Harald Hovdal, Kaur Kamaljit, Jan Schepel, Roelfien Ida Hogenesch, Stephan Schüler, Francis Odeh, Karl B. Alstadhaug, Olav Korsgaard, Elisabeth Farbu, Teis Barclay Ingvaldsen, Diana Soares (SCO), José Rente, José Manuel Costa Guerra, Armando Morganho, António Leitão, João de Sá, Maria José Sá, Pinto Marques, Mário Veloso, Miguel Viana Baptista, Jarmila Szilasiová, Daniela Copikova-Cudrakova, Lubica Prochazkova, Eleonóra Klimová, Vladimir Donath, Miroslav Brozman, Cristina Ramo, Domingo Pérez Ruiz, Carmen Calles Hernández, María Eugenia Marzo Sola, Roberto Suarez Moro, Jose Antonio Vidal, Ana Belén Caminero Rodríguez, Gisela Martin Ozaeta, Jordi Batlle Nadal, Amaya Alvarez de Arcaya Esquide, Javier Olascoaga Urtaza, Sergio Martínez-Yélamos, Txomin Arbizu, Lluis Ramio i Torrenta, Mike Boggild, Martin Wilson, Adnan Al-Araji, Richard Nicholas, Timothy Harrower, Ian Redmond, Tilo Wolf, Michael Osei-Bonsu, Gordon Mazibrada, David Rog, David Cottrell, Cris Constantinescu, Orla Gray, Mohamed Belhag, Abdullah Shehu, Waqar Rashid, Martin Duddy, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Clinical sciences, Neurology, and UCL - (SLuc) Service de neurologie

Subjects
Adult, Male, medicine.medical_specialty, Disability worsening, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, immune system diseases, Internal medicine, Medicine, Humans, Immunologic Factors, In patient, Disability progression, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Medicine(all), Natalizumab/therapeutic use, Expanded Disability Status Scale, business.industry, Multiple sclerosis, General Medicine, Multiple Sclerosis, Relapsing-Remitting/drug therapy, medicine.disease, Immunologic Factors/therapeutic use, Clinical Practice, Treatment Outcome, Neurology, Disease Progression, Observational study, Female, Relapsing-remitting multiple sclerosis, Neurology (clinical), business, EDSS milestones, 030217 neurology & neurosurgery, medicine.drug, Follow-Up Studies
Abstract

Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance.

Published
2018

13. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial

Author

Coles, Alasdair J., Twyman, Cary L., Arnold, Douglas L., Cohen, Jeffrey A., Christian, Confavreux, Fox, Edward J., Hans Peter Hartung, Eva, Havrdova, Selmaj, Krzysztof W., Weiner, Howard L., Tamara, Miller, Elizabeth, Fisher, Rupert, Sandbrink, Lake, Stephen L., Margolin, David H., Pedro, Oyuela, Panzara, Michael A., Compston, D Alastair S., Gupta, the CARE MS II investigators: Ajay S., Edward, Fox, Glyman, Steven A., Thoits, Timothy K., Sullivan, Herman C., Cascione, Mark C., Rammohan, Kottil W., Gazda, Suzanne K., Wynn, Daniel R., Wray, Sibyl E., Stanton, Elias, Ford, Corey C., Andrew, Goodman, Hughes, Bruce L., Omar Azhar Khan, Vaishnav, Anand G., Stephen, Kirzinger, Lynch, Sharon G., Mattson, David H., Braley, Tiffany J., Mikol, Daniel D., Stephen, Krieger, Tamara Ann Miller, Riskind, Peter N., Roberto, Bomprezzi, Wingerchuk, Dean M., Brian, Steingo, Jeffrey Alan Cohen, Crayton, Heidi J., Cooper, Joanna A., Weiner, Leslie P., Harold Moses, J. r., Agius, Mark A., Ann Doan Do Bass, Lallana, Enrico C., Mitchell, Galen W., Krolczyk, Stanley J., Alireza, Minagar, Burk, Jubelt, Evans, Bradley K., Hunter, Samuel F., Rizvi, Syed A., Sheppard, Christopher A., David Honeycutt, W. M., Joseph, Herbert, Lathi, Ellen S., Gabriel, Pardo, Lily Jung Ilenson, Rothstein, Ted L., Thrower, Ben W., Mary Ann Picone, Mariko, Kita, Grazioli, Erica M., Silliman, Scott L., Thomas, Giancarlo, Gottesman, Malcolm H., Abou Zeid, Nuhad E., Rowe, Vernon D., Boutwell, Christine M., Schaeffer, John D., Riley, Claire S., Edwards, Keith R., Wendt, Jeanette K., G. Kim Bigley J. r., Shubin, Richard A., Silva Markovic Plese, Jones, Davis E., Gary, Clauser, Freedman, Mark S., Francois, Grand’Maison, Jacques, Francois H., Traboulsee, Anthony L., Brunet, Donald G., Marcelo, Kremenchutzky, Charles, Ayotte, Lava, Neil S., Waldman, Stephen R., Janus, Todd J., Stephen Gerard Vincent, Mark, Gudesblatt, Michael, Rossen, Stein, Lee S., Bennett Irving Machanic, Timothy, Vollmer, Gitt, Jeffrey S., Jeffrey, Dunn, Donald, Negroski, Fletcher, Mark H., Adil, Javed, Frohman, Elliot M., Richard, Macdonell, John Owen King, Paine, Mark A., Karyn, Boundy, Simon, Broadley, Steve, Vucic, Stephen, Reddel, Dreyer, Michael D., Raymond, Schwartz, Pamela Ann McCombe, Suzanne, Hodgkinson, Charles, Tilbery, Ferreira, Maria Lucia B., Dagoberto, Callegaro, Marcio Mena Barreto Martins, Jesus Arturo Violante Villanueva, Noemi Santos Caballero, Claudia Venzor Mendoza, Norma Haydee Deri, Alasdair, Coles, Neil James Scolding, Gavin, Giovannoni, Basil, Sharrack, Rog, David J., Giancarlo, Comi, Angelo, Ghezzi, Mancardi, Giovanni L., Durelli, Luca, Antonio, Bertolotto, Ruggero, Capra, Carlo, Pozzilli, Maria Giovanna Marrosu, Hupperts, Raymond M. M., Erik van Munster, Xavier, Montalbán, Rafael Arroyo González, Guillermo Izquierdo Ayuso, Óscar Fernández Fernández, Patrick, Vermersch, Jerome de Seze, Thibault, Moreau, Pierre, Clavelou, Catherine, Lubetzki, Michel, Clanet, Marc, Debouverie, Gilles, Edan, Judith, Haas, Martin, Stangel, Tjalf, Ziemssen, Bernhard, Hemmer, Karl, Baum, Klaus Zettl, U., Herrlinger, U., Wolfgang, Köhler, Gunter, Ochs, Patrick, Oschmann, Klaus Tiel Wilck, Hayrettin, Tumani, Urban, Peter P., Jan, Lycke, Anders, Svenningsson, Ivana, Kovarova, Marta, Vachova, Ivan, Rektor, Radomir, Talab, Krzysztof, Selmaj, Zbigniew, Stelmasiak, Wojciech, Kozubski, Dubois, Benedicte D. P., Dominique, Dive, Christian, Sindic, Karl, Vass, Per Soelberg Sørensen, Thor, Petersen, Mads, Ravnborg, Anat, Achiron, Adi Vaknin Dembinsky, Arnon, Karni, Gusev, Evgeny I., Stolyarov, Igor D., Zavalishin, Igor A., Skoromets, Alexander A., Boyko, Alexei N., Belova, Anna N., Malkova, Nadezhda A., Barantsevich, Evgeniy R., Yakupov, Eduard Z., Perfiliev, Semen V., Poverennova, Irina E., Voloshyna, Natalia P., Nehrych, Tetyana I., Kobys, Tetyana O., Mario, Habek, Vesna, Brinar, Zlatko, Trkanjec, Anton, Vladić, Spomenka Kidemet Piskać, Licia, Antonelli, Jelena, Drulović, Čongor, Nadj, Evica, Dinčić, Gordana, Tončev, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs School for Mental Health and Neuroscience, Radiology and nuclear medicine, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases

Subjects
Male, Adult, medicine.medical_specialty, Adolescent, CD52, multiple sclerosis, Administration, Cutaneous, Antibodies, Monoclonal, Humanized, law.invention, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Randomized controlled trial, Recurrence, law, Internal medicine, Humans, Medicine, Glatiramer acetate, Infusions, Intravenous, Adverse effect, Alemtuzumab, disease, business.industry, Multiple sclerosis, Interferon beta-1a, Glatiramer Acetate, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Immunology, Female, Ocrelizumab, Peptides, business, Immunosuppressive Agents, medicine.drug
Abstract

The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 [95% CI 0·39-0·65]; p0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 [95% CI 0·38-0·87]; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%] of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia.For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity.Genzyme (Sanofi) and Bayer Schering Pharma.

Published
2012
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14. Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry.

Author

Potuznik, Pavel, Drahota, Jiri, Horakova, Dana, Peterka, Marek, Mazouchova, Aneta, Matyas, David, Pavelek, Zbysek, Vachova, Marta, Recmanova, Eva, Stetkarova, Ivana, Libertinova, Jana, Mares, Jan, Stourac, Pavel, Grunermelova, Marketa, Martinkova, Alena, Adamkova, Jana, Hradilek, Pavel, Ampapa, Radek, Dufek, Michal, and Kubala Havrdova, Eva

Abstract

Background: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). Objectives: Provide experience with cladribine therapy in a real-world setting. Methods: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. Results: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was.67. Following cladribine initiation, the ARR decreased to.28 in the first year and.22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was.25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. Conclusion: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Reports from Charles University Highlight Recent Research in Multiple Sclerosis (Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry).

Subjects
CENTRAL nervous system diseases, DRUG therapy, MULTIPLE sclerosis, PATIENT compliance
Abstract

A recent study conducted by Charles University in the Czech Republic examined the real-world effectiveness of cladribine as a treatment for multiple sclerosis (MS). The study analyzed data from the Czech nationwide registry ReMuS and found that cladribine therapy was effective in reducing relapse rates and maintaining stable disability status in patients with MS. The study also highlighted the high adherence rate to cladribine treatment. These findings confirm the efficacy of cladribine in real-world settings, particularly in patients who have previously received other treatments. The study emphasizes the importance of registry-based studies in capturing real-world clinical practice. [Extracted from the article]

Published
2024

16. Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder.

Author

Aktas, Orhan, Hartung, Hans-Peter, Smith, Michael A., Rees, William A., Kazuo Fujihara, Paul, Friedemann, Marignier, Romain, Bennett, Jeffrey L., Ho Jin Kim, Weinshenker, Brian G., Pittock, Sean J., Wingerchuk, Dean M., Cutter, Gary, Dewei She, Gunsior, Michele, Cimbora, Daniel, Katz, Eliezer, and Cree, Bruce A.

Subjects
NEUROMYELITIS optica, COLUMBIA-Suicide Severity Rating Scale, MEDICAL personnel, HEALTH Insurance Portability & Accountability Act, MEDICAL terminology
Published
2023
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17. Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide.

Author

Štrosová, Daniela, Tužil, Jan, Turková, Barbora Velacková, Pilnáčková, Barbora Filková, de Souza, Lada Lžičařová, Doležalová, Helena, Rašková, Michaela, Dufek, Michal, and Doležal, Tomáš

Subjects
FINGOLIMOD, PATIENT preferences, QUALITY of life, ORAL drug administration, PATIENT compliance, ATTITUDE (Psychology)
Abstract

Background: A poor patient adherence often limits the real-world effectiveness of an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). In the present study, we aimed to map patient preferences, attitudes toward treatment, and quality of life to identify the predictors of non-adherence to teriflunomide. Methods: This was a single-arm, non-interventional, multicenter study (Czech Act 378/2007 Coll.) consisting of three visits: the first at treatment initiation (teriflunomide 14 mg), and then after 3 and 9 months of therapy. We enrolled both DMT-naïve and patients who had undergone a DMT diagnosed with a clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). The functional status and MS activity were estimated using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR); the quality of life via the Multiple Sclerosis Impact Scale (MSIS-29); the medication adherence with the Morisky Medication Adherence Scale (MMAS-8); the confidence in the ability to take medications by the Self-Efficacy for Appropriate Medication Score (SEAMS); and the attitude to the therapy via the Beliefs about Medicines Questionnaire (BMQ). After nine months of therapy, we predicted the adherence to teriflunomide (MMAS-8) by fitting a multivariate ordinal logistic model with EDSS changes, gender, previous DMT, MSIS-29, BMQ, and SEAMS as the explanatory variables. Results: Between 2018 and 2019, 114 patients were enrolled at 10 sites in the Czech Republic. The mean age was 41.2 years, 64.8% were diagnosed with a CIS, 52.4% were DMT-naïve, and 98.1% of patients preferred an oral administration at the baseline. The mean EDSS baseline was 1.97 and remained constant during the 9 months of therapy. The ARR baseline was 0.72 and dropped to 0.19 and 0.15 after 3 and 9 months, respectively. Despite a more than 4-fold higher ARR baseline, the treatment-naïve patients achieved an ARR at 9 months comparable with those previously treated. There were ten non-serious adverse reactions. After nine months of teriflunomide therapy, 63.3%, 21.2%, and 15.4% of patients had a high, medium, and low adherence, respectively, as per the MMAS-8; 100% of patients preferred an oral administration. The SEAMS score (odds ratio (OR) = 0.91; p = 0.013) and previous DMT (OR = 4.28; p = 0.005) were the only significant predictors of non-adherence. The disability, the quality of life, and beliefs about medicines had no measurable effect on adherence. Conclusion: After nine months of teriflunomide therapy, both the disability and quality of life remained stable; the relapse rate significantly decreased, 63.3% of patients had a high adherence, and 100% of patients preferred an oral administration. A low adherence was associated with previous DMT experiences and a low self-efficacy for the appropriate medication (i.e., the confidence in one's ability to take medication correctly). [ABSTRACT FROM AUTHOR]

Published
2022
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18. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

Author

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

Subjects
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 (C max) 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 AUC τ , 487.7 vs 474.1 h × µg/mL (ratio 1.03); C max, 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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19. Clinical outcomes in patients who discontinue natalizumab therapy after 2 years in the Tysabri ® Observational Program (TOP).

Author

Butzkueven, Helmut, Trojano, Maria, Kappos, Ludwig, Spelman, Tim, Wiendl, Heinz, Rosales, Karen, Su, Ray, Licata, Stephanie, Ho, Pei-Ran, and Campbell, Nolan

Subjects
NATALIZUMAB, TREATMENT effectiveness, DISEASE risk factors, MULTIPLE sclerosis
Abstract

Background: Natalizumab is a highly efficacious therapy for relapsing–remitting multiple sclerosis (RRMS). Patients who discontinue natalizumab may experience return of MS disease activity. Objective: The aim of this study was to analyze predictors of post-natalizumab disease activity return. Methods: The Tysabri® Observational Program (TOP) is an ongoing observational study of natalizumab-treated RRMS patients. Patients discontinuing natalizumab are encouraged to remain in TOP. Results: Analyses included 3221 TOP patients. After ⩾2 years on natalizumab, relapse risk was twice as high for patients who switched to an oral therapy (n = 660, hazard ratio (HR) = 2.18, p < 0.001) and three times as high for patients who switched to an injectable therapy (n = 95, HR = 3.02, p < 0.001) as for those who stayed on natalizumab (n = 2466). Relapse rates after switching remained below pre-natalizumab rates. In patients who switched to an oral therapy, higher relapse risk was predicted by longer washout time, more pre-natalizumab relapses, higher Expanded Disability Status Scale score at natalizumab initiation, and shorter natalizumab treatment duration. Conclusion: Patients who stayed on natalizumab had better clinical outcomes than those who switched to an oral or injectable therapy after ⩾2 years on natalizumab. These results highlight modifiable risk factors for disease activity return (e.g. natalizumab treatment duration and washout duration) to consider when making treatment decisions. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Long-term safety and efficacy of daclizumab beta in relapsing–remitting multiple sclerosis: 6-year results from the SELECTED open-label extension study.

Author

Gold, Ralf, Radue, Ernst-Wilhelm, Giovannoni, Gavin, Selmaj, Krzysztof, Havrdova, Eva Kubala, Montalban, Xavier, Stefoski, Dusan, Sprenger, Till, Robinson, Randy R., Fam, Sami, Smith, Jonathan, Chalkias, Spyros, Giannattasio, Giorgio, Lima, Gabriel, and Castro-Borrero, Wanda

Subjects
MULTIPLE sclerosis, TREATMENT effectiveness, PATIENT selection, CONFIDENCE intervals, ENCEPHALITIS
Abstract

Objective: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. Methods: Eligible participants who completed 1–2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. Results: Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0–24 was 0.21 (0.16–0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. Conclusions: The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. Trial registration: Clinicaltrials.gov NCT01051349; first registered on January 15, 2010. [ABSTRACT FROM AUTHOR]

Published
2020
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21. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP).

Author

Butzkueven, Helmut, Kappos, Ludwig, Wiendl, Heinz, Trojano, Maria, Spelman, Tim, Ih Chang, Kasliwal, Rachna, Jaitly, Seema, Campbell, Nolan, Pei-Ran Ho, Licata, Stephanie, Chang, Ih, Ho, Pei-Ran, and Tysabri Observational Program (TOP) Investigators

Subjects
MULTIPLE sclerosis, DISEASE progression, RESEARCH, RESEARCH methodology, DISABILITY evaluation, EVALUATION research, MEDICAL cooperation, TREATMENT effectiveness, COMPARATIVE studies, IMMUNOLOGICAL adjuvants
Abstract

Objective: The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients.Methods: These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP.Results: As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0-11.6) years; median follow-up time was 5.2 (range 0-10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias.Conclusions: Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab.Trial Registration Number: NCT00493298. [ABSTRACT FROM AUTHOR]

Published
2020
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22. ECTRIMS 2019 - Poster Session 2.

Subjects
POSTER presentations, CEREBRAL small vessel diseases, LEUKOCYTE count
Abstract

Central pons lesions were increased slightly in 8.3% (9 out of 93) MS with VRF cases (mostly smokers) and specificity was reduced to 90.32 % 95%CI 82.4, 94.5, when MS with VRF was compared with non-MS with VRF. B Conclusions: b Although pons lesions are seen in a minority of patients, the presence of peripheral pons lesions is a useful discriminator for MS from vascular associated lesions and specificity does not seem to be influence by the presence of VRF in MS. The MS-severity-score, 5.15 vs. 0.88 (p=0.019), the T2 brainstem-, 1 vs. 0 (p=0.041), and the total intracranial contrast-enhancing lesion counts, 2 vs. 0 (p=0.000), were higher in patients with cranial nerve enhancement, compared to age-, disease duration-, and gender- matched MS patients. The analysis included patients with non-inflammatory neurological diseases (non-MS, n=29) and new onset multiple sclerosis (MS, n=42). [Extracted from the article]

Published
2019
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23. Bolest u roztroušené sklerózy.

Author

Vachová, Marta

Abstract

Copyright of Neurologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2020

25. Daclizumab high-yield process in the treatment of relapsing-remitting multiple sclerosis.

Author

Preiningerova, Jana Lizrova and Vachova, Marta

Abstract

Daclizumab is a humanized monoclonal antibody that binds to the α subunit (CD25) of the interleukin-2 receptor and favorably modulates the immune environment in multiple sclerosis (MS). Blockage of CD25, among other effects, causes expansion and enhanced function of regulatory CD56bright natural killer cells, which seems to be the leading mechanism of action in MS. Phase II and III clinical trials have demonstrated that monthly subcutaneous injections of daclizumab high yield process (DAC HYP) 150 mg in patients with relapsing MS led to a significant reduction of annualized relapse rate and decreased number of contrast- enhanced lesions on brain magnetic resonance imaging. Treatment with DAC HYP had efficacy superior to treatment with weekly injections of interferon β1a. This review summarizes the development of and clinical experience with daclizumab in MS. [ABSTRACT FROM AUTHOR]

Published
2017
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26. ePosters.

Subjects
MULTIPLE sclerosis, NEUROMYELITIS optica, DISEASE relapse
Abstract

The article presents abstracts on topics related to multiple sclerosis (MS) including the not-MS diagnoses, the neurovascular coupling in relapsing-remitting MS and the use of optical coherence tomography in differentiating patients with MS and neuromyelitis optica spectrum disorder.

Published
2016
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27. Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study.

Author

Gold, Ralf, Radue, Ernst-Wilhelm, Giovannoni, Gavin, Selmaj, Krzysztof, Havrdova, Eva, Stefoski, Dusan, Sprenger, Till, Montalban, Xavier, Cohan, Stanley, Umans, Kimberly, Greenberg, Steven J., Ozen, Gulden, and Elkins, Jacob

Subjects
DRUG efficacy, MULTIPLE sclerosis, URINARY tract infections, INTERLEUKIN-2, ULCERATIVE colitis, SELECTION bias (Statistics), PATIENTS, THERAPEUTIC use of immunoglobulins, THERAPEUTIC use of monoclonal antibodies, SUBCUTANEOUS injections, ASPARTATE aminotransferase, BRAIN, CLINICAL trials, COMPARATIVE studies, DRUG eruptions, IMMUNOGLOBULINS, IMMUNOSUPPRESSIVE agents, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, MONOCLONAL antibodies, NASOPHARYNX diseases, PNEUMONIA, RESEARCH, RESPIRATORY infections, SAFETY, DISEASE relapse, EVALUATION research, ALANINE aminotransferase, TREATMENT effectiveness, THERAPEUTICS
Abstract

Background: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study.Methods: An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study.Results: The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%).Conclusions: The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded.Trial Registration: Clinicaltrials.gov NCT01051349; first registered January 15, 2010. [ABSTRACT FROM AUTHOR]

Published
2016
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29. Poster Session 1.

Subjects
METHYL aspartate receptors, CORPUS callosum, RITUXIMAB
Abstract

The article presents several abstracts of articles related to multiple sclerosis including "NMDA receptor antibodies are a rare condition in inflammatory demyelinating diseases," by M. Ram and colleagues, "Corpus callosum lesions in patients with a clinical isolated syndrome," by N. A. Cerdá-Fuertes and colleagues, and "Efficacy of rituximab in refractory neuromyelitis optica," by D. Brassat and colleagues.

Published
2015
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30. 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

Author

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

Subjects
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

Published
2021
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31. Disease-activity-free status in patients with relapsing–remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.

Author

Havrdova, Eva, Giovannoni, Gavin, Stefoski, Dusan, Forster, Samantha, Umans, Kimberly, Mehta, Lahar, Greenberg, Steven, and Elkins, Jacob

Subjects
PLACEBOS, IMMUNOGLOBULINS, DRUG side effects, MULTIPLE sclerosis treatment, THERAPEUTICS
Abstract

The article presents a study which examines the proportion between daclizumab high-yield process (DAC HYP) and placebo-treated patients with multiple sclerosis. SELECT randomized, double-blind trial was applied to conduct the assessment. More DAC HYP-treated patients were found to be disease-activity free than those placebo-treated ones.

Published
2014
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32. Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.

Author

Giovannoni, Gavin, Radue, Ernst-Wilhelm, Havrdova, Eva, Riester, Katherine, Greenberg, Steven, Mehta, Lahar, and Elkins, Jacob

Subjects
MULTIPLE sclerosis research, DEMYELINATION, DRUG therapy, TREATMENT effectiveness, MAGNETIC resonance imaging
Abstract

Patients with highly active relapsing-remitting multiple sclerosis (RRMS) are at greater risk for disease progression and may respond differently to MS therapeutics than those with less active disease. The current post hoc analysis evaluated the effects of daclizumab high-yield process (DAC HYP) vs. placebo in patients with highly active RRMS in the SELECT study. Highly active RRMS was defined as patients with ≥2 relapses in the year before randomization and ≥1 gadolinium-enhancing (Gd) lesion at baseline. Because results were similar in the DAC HYP dose groups, data from the DAC HYP arms were pooled for analysis. Treatment with DAC HYP resulted in similar effects in highly active ( n = 88) and less active ( n = 506) RRMS patients. DAC HYP reduced the annualized relapse rate by 50 % and 51 % in the highly active ( p = 0.0394) and less active ( p < 0.0001) groups vs. placebo, respectively (interaction p = 0.82). DAC HYP reduced new/newly-enlarging T2 lesions (highly active RRMS 76 % reduction, p < 0.0001; less active RRMS 73 % reduction, p < 0.0001; interaction p = 0.18), the risk of having more Gd lesions (highly active RRMS 89 % reduction, p < 0.0001; less active RRMS 86 % reduction, p < 0.0001; interaction p = 0.46), and sustained disability progression (highly active RRMS 88 % reduction, p = 0.0574; less active RRMS 46 % reduction, p = 0.0383; interaction p = 0.22) vs. placebo. DAC HYP efficacy was similar across the spectrum of MS disease activity as assessed prior to treatment initiation. [ABSTRACT FROM AUTHOR]

Published
2014
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33. Recommendations for the Use of Prolonged-Release Fampridine in Patients with Multiple Sclerosis ( MS).

Author

Preiningerova, Jana Lizrova, Baumhackl, Ulf, Csepany, Tunde, Czaplinski, Adam, Deisenhammer, Florian, Derfuss, Tobias, Fabjan, Tanja H., Fazekas, Franz, Fuchs, Siegrid, Havrdova, Eva, Ledinek, Alenka Horvath, Illes, Zsolt, Jazbec, Sasa Sega, Klimova, Eleonora, Komoly, Samuel, Kurca, Egon, Linnebank, Michael, Lisy, Lubomir, Mares, Jan, and Prochazkova, Lubica

Subjects
MULTIPLE sclerosis, AMINOPYRIDINES, POTASSIUM antagonists, DRUG administration, HUMAN locomotion, CENTRAL nervous system, PATIENTS, THERAPEUTICS
Abstract

Prolonged-release fampridine (fampridine PR) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system. Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis. This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice, prediction, and evaluation of response to treatment and patient management. [ABSTRACT FROM AUTHOR]

Published
2013
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34. Cost of multiple sclerosis in the Czech Republic: The COMS study.

Author

Blahova Dusankova, J, Kalincik, T, Dolezal, T, Kobelt, G, and Havrdova, E

Subjects
MULTIPLE sclerosis, DIRECT costing, OVERHEAD costs, DISABILITIES
Abstract

Background: Information about cost of multiple sclerosis (MS) is available from a number of European countries, but no data from the Czech Republic have been published so far.Objective: The objective of this study was to establish the cost of MS in the Czech Republic, overall and by level of disease severity.Methods: Data on demographics, disease history, resource consumption and production losses were collected from 909 patients recruited in 7 MS centres in the Czech Republic. Annual costs were estimated in the societal perspective, using 2007 unit costs. To evaluate the relationship between disability and costs, patients were stratified into those with mild (67%), moderate (27%) and severe (10%) disability using the Expanded Disability Status Scale.Results: Mean total annual costs per patient were €12,272, of which 51% were direct medical costs, 4% direct non-medical costs and 45% indirect costs. The average annual costs in patients with mild, moderate and severe disability amounted to €9905, €14,064 and €22,880, respectively.Conclusion: The total costs of MS in the Czech Republic are estimated at €208.6 million per year. Consistent with other studies, the costs increase significantly with the severity of MS. [ABSTRACT FROM AUTHOR]

Published
2012
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35. Reports from Charles University Highlight Recent Research in Multiple Sclerosis (Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry)

Subjects
Charles University -- Evaluation, Care and treatment, Evaluation, Research, Neurosciences -- Research, Multiple sclerosis -- Research -- Care and treatment, Antineoplastic agents -- Research -- Evaluation, Antimitotic agents -- Research -- Evaluation
Abstract

2024 AUG 16 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- Data detailed on multiple sclerosis have been presented. According to news reporting from [...]

Published
2024

36. Findings in Life Science Reported from University of Ostrava (Is Pregnancy In Ms Patients Safe and What Is Its Impact On Ms Course? Real World Evidence of 1533 Pregnancies In Czech Republic)

Subjects
Women -- Health aspects, Pregnancy -- Analysis, Pregnant women -- Analysis, Family planning -- Analysis, Health, Women's issues/gender studies
Abstract

2022 JUN 16 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Current study results on Life Science have been published. According to news reporting from [...]

Published
2022

37. Investigators from Charles University of Prague Target COVID-19 (To Be or Not To Be Vaccinated: the Risk of Ms or Nmosd Relapse After Covid-19 Vaccination and Infection)

Subjects
Complications and side effects, Risk factors, Coronaviruses, Infection -- Risk factors -- Complications and side effects, Vaccination, Multiple sclerosis -- Complications and side effects -- Risk factors, COVID-19 -- Risk factors -- Complications and side effects
Abstract

2022 SEP 11 (NewsRx) -- By a News Reporter-Staff News Editor at Medical Letter on the CDC & FDA -- Fresh data on Coronavirus - COVID-19 are presented in a [...]

Published
2022

38. Research Conducted at University of Pennsylvania Has Updated Our Knowledge about Multiple Sclerosis (Rapid and Sustained B-cell Depletion With Subcutaneous Ofatumumab In Relapsing Multiple Sclerosis: Aplios, a Randomized Phase-2 Study)

Subjects
Novartis AG, University of Pennsylvania, Research, Medical research, Immunotherapy -- Research, Pharmaceutical industry -- Research, Multiple sclerosis -- Research, Ofatumumab -- Research, Medicine, Experimental
Abstract

2021 DEC 8 (NewsRx) -- By a News Reporter-Staff News Editor at Immunotherapy Weekly -- Researchers detail new data in Autoimmune Diseases and Conditions - Multiple Sclerosis. According to news [...]

Published
2021

39. Researchers from Charles University of Prague Report New Studies and Findings in the Area of COVID-19 (Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder and Covid-19: a Pandemic Year In Czechia)

Subjects
Research, Risk factors, Neuromyelitis optica -- Research -- Risk factors, Coronaviruses -- Research, COVID-19 -- Risk factors -- Research
Abstract

2021 NOV 1 (NewsRx) -- By a News Reporter-Staff News Editor at Pain & Central Nervous System Week -- A new study on Coronavirus - COVID-19 is now available. According [...]

Published
2021

40. Charles University Prague Researchers Provide Details of New Studies and Findings in the Area of Multiple Sclerosis (Comparison of Therapies in MS Patients After the First Demyelinating Event in Real Clinical Practice in the Czech Republic: ...)

Subjects
Care and treatment, Research, Comparative analysis, Viral antigens -- Comparative analysis -- Research, Interferon -- Research -- Comparative analysis, Multiple sclerosis -- Care and treatment -- Research, Teriflunomide -- Research
Abstract

2021 JAN 29 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- Researchers detail new data in multiple sclerosis. According to news originating from Charles [...]

Published
2021

41. Roche's Tomas Votruba to head drug makers' association MAFS

Subjects
Roche Holding AG, Pharmaceutical industry, Business, Business, international
Abstract

(From Czech News Agency) PRAGUE, April 11 (CTK) - Tomas Votruba, the chief executive of the Roche company, became the chairman of the International Association of Pharmaceutical Companies MAFS on [...]

Published
2003

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