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2. Prevalence, Treatment and Correlates of Depression in Multiple Sclerosis

Author

Young, Carolyn A, primary, Langdon, Dawn, additional, Rog, David, additional, Chhetri, Suresh Kumar, additional, Tanasescu, Radu, additional, Kalra, Seema, additional, Webster, Gillian, additional, Nicholas, Richard, additional, Ford, Helen L, additional, Woolmore, John, additional, Paling, David, additional, Tennant, Alan, additional, and Mills, Roger, additional

Published
2024
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3. Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study

Author

Rog, David, primary, Brownlee, Wallace, additional, Carod-Artal, Francisco Javier, additional, Kalra, Seema, additional, Barker, Noreen, additional, Lowndes, Claire, additional, Pendlebury, Jessica, additional, Leclerc, Stephanie, additional, Amin, Amerah, additional, Ashton, Luke, additional, Evans, Hannah, additional, and De Cock, Erwin, additional

Published
2024
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6. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial

Author

Foley, John F, primary, Defer, Gilles, additional, Ryerson, Lana Zhovtis, additional, Cohen, Jeffrey A, additional, Arnold, Douglas L, additional, Butzkueven, Helmut, additional, Cutter, Gary, additional, Giovannoni, Gavin, additional, Killestein, Joep, additional, Wiendl, Heinz, additional, Smirnakis, Karen, additional, Xiao, Shan, additional, Kong, George, additional, Kuhelj, Robert, additional, Campbell, Nolan, additional, van der Walt, Anneke, additional, Dwyer, Christopher, additional, Buzzard, Katherine, additional, Spies, Judith, additional, Parratt, John, additional, van Pesch, Vincent, additional, Willekens, Barbara, additional, Perrotta, Gaetano, additional, Bartholomé, Emmanuel, additional, Grand'Maison, Francois, additional, Jacques, Francois, additional, Giacomini, Paul, additional, Vosoughi, Reza, additional, Girard, Jean-Marc, additional, de Seze, Jerome, additional, Lebrun Frenay, Christine, additional, Ruet, Aurelie, additional, Laplaud, David-Axel, additional, Reifschneider, Gerd, additional, Wagner, Bert, additional, Rauer, Sebastian, additional, Pul, Refik, additional, Seipelt, Maria, additional, Berthele, Achim, additional, Klotz, Luisa, additional, Kallmann, Boris-Alexander, additional, Paul, Friedemann, additional, Achiron, Anat, additional, Lus, Giacomo, additional, Centonze, Diego, additional, Patti, Francesco, additional, Grimaldi, Luigi, additional, Hupperts, Raymond, additional, Frequin, Stephan, additional, Fermont, Jiske, additional, Madueno, Sara Eichau, additional, Alonso Torres, Ana Maria, additional, Costa-Frossard França, Lucienne, additional, Meca-Lallana, Jose Eustasio, additional, Ruiz, Luis Brieva, additional, Pearson, Owen, additional, Rog, David, additional, Evangelou, Nikolaos, additional, Ismail, Azza, additional, Lathi, Ellen, additional, Fox, Edward, additional, Leist, Thomas, additional, Sloane, Jacob, additional, Wu, Gregory, additional, Khatri, Bhupendra, additional, Steingo, Brian, additional, Thrower, Ben, additional, Gudesblatt, Mark, additional, Calkwood, Jonathan, additional, Bandari, Daniel, additional, Scagnelli, John, additional, Laganke, Christopher, additional, Robertson, Derrick, additional, Kipp, Lucas, additional, Belkin, Martin, additional, Cohan, Stanley, additional, Goldstick, Lawrence, additional, Courtney, Ardith, additional, Vargas, Wendy, additional, Sylvester, Andrew, additional, Srinivasan, Jayshri, additional, Kannan, Meena, additional, Picone, Maryann, additional, English, Jeffrey, additional, Napoli, Salvatore, additional, Balabanov, Roumen, additional, Zaydan, Islam, additional, Nicholas, Jacqueline, additional, Kaplan, Jeffrey, additional, Lublin, Fred, additional, Riser, Emily, additional, Miller, Tamara, additional, Alvarez, Enrique, additional, Wray, Sibyl, additional, Gross, Jeffrey, additional, Pawate, Siddharama, additional, Hersh, Carrie, additional, McCarthy, Lucas, additional, Crayton, Heidi, additional, and Graves, Jennifer, additional

Published
2022
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7. Evaluating the feasibility of a real world pharmacovigilance study (OPTIMISE:MS)

Author

Dobson, Ruth, primary, Craner, Matthew, additional, Waddingham, Ed, additional, Miller, Aleisha, additional, Pindoria, Jayant, additional, Cavey, Ana, additional, Blain, Camilla, additional, De Luca, Gabriele, additional, Evangelou, Nikos, additional, Ford, Helen, additional, Gallagher, Paul, additional, George, Katila, additional, Geraldes Ramos Dias, Ruth, additional, Harman, Paula, additional, Hobart, Jeremy, additional, King, Tanya, additional, Linighan, Ruth, additional, MacDougall, Niall, additional, Marta, Monica, additional, Mitchell, Stephanie, additional, Nicholas, Richard, additional, Rog, David, additional, Scalfari, Antonio, additional, Scolding, Neil, additional, Webb, Stewart, additional, White, Sarah, additional, Wilton, Judith, additional, Young, Carolyn, additional, and Matthews, Paul M, additional

Published
2022
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8. The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications

Author

Young, Carolyn A., primary, Mills, Roger, additional, Langdon, Dawn, additional, Sharrack, Basil, additional, Majeed, Tahir, additional, Kalra, Seema, additional, Footitt, David, additional, Rog, David, additional, Harrower, Tim, additional, Nicholas, Richard, additional, Woolmore, John, additional, Thorpe, John, additional, Hanemann, C. Oliver, additional, Ford, Helen, additional, Paling, David, additional, Ellis, Cathy, additional, Palace, Jackie, additional, Constantinescu, Cris, additional, and Tennant, Alan, additional

Published
2022
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12. Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study

Author

Brown, J William L, primary, Cunniffe, Nick G, additional, Prados, Ferran, additional, Kanber, Baris, additional, Jones, Joanne L, additional, Needham, Edward, additional, Georgieva, Zoya, additional, Rog, David, additional, Pearson, Owen R, additional, Overell, James, additional, MacManus, David, additional, Samson, Rebecca S, additional, Stutters, Jonathan, additional, ffrench-Constant, Charles, additional, Gandini Wheeler-Kingshott, Claudia A M, additional, Moran, Carla, additional, Flynn, Paul D, additional, Michell, Andrew W, additional, Franklin, Robin J M, additional, Chandran, Siddharthan, additional, Altmann, Daniel R, additional, Chard, Declan T, additional, Connick, Peter, additional, and Coles, Alasdair J, additional

Published
2021
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13. Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy

Author

Young, Carolyn A., primary, Mills, Roger, additional, Rog, David, additional, Sharrack, Basil, additional, Majeed, Tahir, additional, Constantinescu, Cris S., additional, Kalra, Seema, additional, Harrower, Timothy, additional, Santander, Helen, additional, Courtald, Gillian, additional, Ford, Helen L., additional, Woolmore, John, additional, and Tennant, Alan, additional

Published
2021
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14. COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies

Author

Garjani, Afagh, primary, Middleton, Rodden M, additional, Hunter, Rachael, additional, Tuite-Dalton, Katherine A, additional, Coles, Alasdair, additional, Dobson, Ruth, additional, Duddy, Martin, additional, Hughes, Stella, additional, Pearson, Owen R, additional, Rog, David, additional, Tallantyre, Emma C, additional, das Nair, Roshan, additional, Nicholas, Richard, additional, and Evangelou, Nikos, additional

Published
2021
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16. Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years

Author

Bass, Ann D., primary, Arroyo, Rafael, additional, Boster, Aaron L., additional, Boyko, Alexey N., additional, Eichau, Sara, additional, Ionete, Carolina, additional, Limmroth, Volker, additional, Navas, Carlos, additional, Pelletier, Daniel, additional, Pozzilli, Carlo, additional, Ravenscroft, Jennifer, additional, Sousa, Livia, additional, Tintoré, Mar, additional, Uitdehaag, Bernard M.J., additional, Baker, Darren P., additional, Daizadeh, Nadia, additional, Choudhry, Zia, additional, and Rog, David, additional

Published
2021
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17. The Impact of Smoking Cessation on Multiple Sclerosis Disease Progression

Author

Rodgers, William Jeffrey, primary, Friede, T., additional, Vonberg, Frederick W., additional, Constantinescu, Cris S., additional, Coles, Alasdair, additional, Chataway, J., additional, Duddy, Martin, additional, Emsley, Hedley, additional, Ford, Helen, additional, Fisniku, Leonora, additional, Galea, Ian, additional, Harrower, Timothy, additional, Hobart, Jeremy, additional, Huseyin, H., additional, Kipps, Christopher, additional, Marta, Monica, additional, McDonnell, Gavin, additional, McLean, Brendan, additional, Pearson, Owen R., additional, Rog, David, additional, Schmierer, Klaus, additional, Sharrack, Basil, additional, Straukiene, Agne, additional, Wilson, Hannahej, additional, Ford, D.V., additional, Middleton, Rodden, additional, Nicholas, Richard, additional, and Register Group, The MS, additional

Published
2021
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19. Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years

Author

Oh, Jiwon, primary, Achiron, Anat, additional, Celius, Elisabeth G., additional, Chambers, Christina, additional, Derwenskus, Joy, additional, Devonshire, Virginia, additional, Hellwig, Kerstin, additional, Hutton, George J., additional, McCombe, Pamela, additional, Moore, Marie, additional, Rog, David, additional, Schneider, Jean-Raphael, additional, Simm, Renata Faria, additional, Sousa, Livia, additional, Vincent, Stephen G., additional, Chung, Luke, additional, Daizadeh, Nadia, additional, Mitchell, Colin, additional, and Compston, D. Alastair S., additional

Published
2020
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23. Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting

Author

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

Published
2018
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24. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Author

Kapoor, Raju, primary, Ho, Pei-Ran, additional, Campbell, Nolan, additional, Chang, Ih, additional, Deykin, Aaron, additional, Forrestal, Fiona, additional, Lucas, Nisha, additional, Yu, Bei, additional, Arnold, Douglas L, additional, Freedman, Mark S, additional, Goldman, Myla D, additional, Hartung, Hans-Peter, additional, Havrdová, Eva Kubala, additional, Jeffery, Douglas, additional, Miller, Aaron, additional, Sellebjerg, Finn, additional, Cadavid, Diego, additional, Mikol, Dan, additional, Steiner, Deborah, additional, Bartholomé, Emmanuel, additional, D'Hooghe, Marie, additional, Pandolfo, Massimo, additional, Van Wijmeersch, Bart, additional, Bhan, Virender, additional, Blevins, Gregg, additional, Brunet, Donald, additional, Devonshire, Virginia, additional, Duquette, Pierre, additional, Freedman, Mark, additional, Grand'Maison, François, additional, Jacques, François, additional, Lapierre, Yves, additional, Lee, Liesly, additional, Morrow, Sarah, additional, Yeung, Michael, additional, Dufek, Michal, additional, Kanovsky, Petr, additional, Stetkarova, Ivana, additional, Talabova, Marika, additional, Frederiksen, Jette, additional, Kant, Matthias, additional, Petersen, Thor, additional, Ravnborg, Mads, additional, Airas, Laura, additional, Elovaara, Irina, additional, Eralinna, Juha-Pekka, additional, Sarasoja, Taneli, additional, Al Khedr, Abdullatif, additional, Brassat, David, additional, Brochet, Bruno, additional, Camu, William, additional, Debouverie, Marc, additional, Laplaud, David, additional, Lebrun Frenay, Christine, additional, Pelletier, Jean, additional, Vermersch, Patrick, additional, Vukusi, Sandra, additional, Baum, Karl, additional, Berthele, Achim, additional, Faiss, Juergen, additional, Flachenecker, Peter, additional, Hohlfeld, Reinhard, additional, Krumbholz, Markus, additional, Lassek, Christoph, additional, Maeurer, Mathias, additional, Meuth, Sven, additional, Ziemssen, Tjalf, additional, Hardiman, Orla, additional, McGuigan, Christopher, additional, Achiron, Anat, additional, Karussis, Dimitrios, additional, Bergamaschi, Roberto, additional, Morra, Vincenzo Brescia, additional, Comi, Giancarlo, additional, Cottone, Salvatore, additional, Grimaldi, Luigi, additional, Mancardi, Giovanni Luigi, additional, Massacesi, Luca, additional, Nocentini, Ugo, additional, Salvetti, Marco, additional, Scarpini, Elio, additional, Sola, Patrizia, additional, Tedeschi, Gioacchino, additional, Trojano, Maria, additional, Zaffaroni, Mauro, additional, Frequin, Stephan, additional, Hupperts, Raymond, additional, Killestein, Joep, additional, Schrijver, Hans, additional, Van Dijl, Ronald, additional, van Munster, Erik, additional, Czarnecki, Maciej, additional, Drozdowski, Wieslaw, additional, Fryze, Waldemar, additional, Hertmanowska, Hanka, additional, Ilkowski, Jan, additional, Kaminska, Anna, additional, Klodowska-Duda, Gabriela, additional, Maciejowski, Maciej, additional, Motta, Ewa, additional, Podemski, Ryszard, additional, Potemkowski, Andrzej, additional, Rog, Teresa, additional, Selmaj, Krzysztof, additional, Stelmasiak, Zbigniew, additional, Stepien, Adam, additional, Tutaj, Andrzej, additional, Zaborski, Jacek, additional, Boyko, Alexey, additional, Chefranova, Zanna, additional, Evdoshenko, Evgeny, additional, Khabirov, Farit, additional, Sivertseva, Stella, additional, Yakupov, Eduard, additional, Alvarez Cermeño, Jose Carlos, additional, Escartin, Antonio, additional, Fernandez, Oscar Fernandez, additional, Garcia-Merino, Antonio, additional, Hernandez Perez, Miguel Angel, additional, Ayuso, Guillermo Izquierdo, additional, Lallana, José Meca, additional, Gairin, Xavier Montalban, additional, Oreja-Guevara, Celia, additional, Saiz Hinarejos, Albert, additional, Gunnarsson, Martin, additional, Lycke, Jan, additional, Martin, Claes, additional, Piehl, Fredrik, additional, Roshanisefat, Homayoun, additional, Sundstrom, Peter, additional, Duddy, Martin, additional, Gran, Bruno, additional, Harrower, Timothy, additional, Hobart, Jeremy, additional, Kapoor, Raju, additional, Lee, Martin, additional, Mattison, Paul, additional, Nicholas, Richard, additional, Pearson, Owen, additional, Rashid, Waqar, additional, Rog, David, additional, Sharrack, Basil, additional, Silber, Eli, additional, Turner, Ben, additional, Williams, Anna, additional, Woolmore, John, additional, Young, Carolyn, additional, Bandari, Daniel, additional, Berger, Joseph, additional, Camac, Ann, additional, Cohan, Stanley, additional, Conway, Jill, additional, Edwards, Keith, additional, Fabian, Michelle, additional, Florin, Jack, additional, Freedman, Steven, additional, Garwacki, Dennis, additional, Goldman, Myla, additional, Harrison, Daniel, additional, Herrman, Craig, additional, Huang, Deren, additional, Javed, Adil, additional, Kamin, Stephen, additional, Katsamakis, George, additional, Khatri, Bhupendra, additional, Langer-Gould, Annette, additional, Lynch, Sharon, additional, Mattson, David, additional, Miller, Tamara, additional, Miravalle, Augusto, additional, Moses, Harold, additional, Muley, Suraj, additional, Napier, James, additional, Nielsen, Allen, additional, Pachner, Andrew, additional, Pardo, Gabriel, additional, Picone, MaryAnn, additional, Robertson, Derrick, additional, Royal, Walter, additional, Sheppard, Christopher, additional, Thrower, Ben, additional, Twyman, Cary, additional, Waubant, Emmanuelle, additional, Wendt, Jeanette, additional, Yadav, Vijayshree, additional, Zabad, Rana, additional, and Zarelli, Greg, additional

Published
2018
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25. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Kappos, Ludwig, primary, Bar-Or, Amit, additional, Cree, Bruce A C, additional, Fox, Robert J, additional, Giovannoni, Gavin, additional, Gold, Ralf, additional, Vermersch, Patrick, additional, Arnold, Douglas L, additional, Arnould, Sophie, additional, Scherz, Tatiana, additional, Wolf, Christian, additional, Wallström, Erik, additional, Dahlke, Frank, additional, Achiron, Anat, additional, Achtnichts, Lutz, additional, Agan, Kadriye, additional, Akman-Demir, Gulsen, additional, Allen, Alison B, additional, Antel, Jack P, additional, Antiguedad, Alfredo Rodriguez, additional, Apperson, Michelle, additional, Applebee, Angela M, additional, Ayuso, Guillermo Izquierdo, additional, Baba, Masayuki, additional, Bajenaru, Ovidiu, additional, Balasa, Rodica, additional, Balci, Belgin Petek, additional, Barnett, Michael, additional, Bass, Ann, additional, Becker, Veit U, additional, Bejinariu, Mihaela, additional, Bergh, Florian Then, additional, Bergmann, Arnfin, additional, Bernitsas, Evanthia, additional, Berthele, Achim, additional, Bhan, Virender, additional, Bischof, Felix, additional, Bjork, Randall John, additional, Blevins, Gregg, additional, Boehringer, Matthias, additional, Boerner, Thomas, additional, Bonek, Robert, additional, Bowen, James D, additional, Bowling, Allen, additional, Boyko, Alexey N, additional, Boz, Cavit, additional, Bracknies, Vera, additional, Braune, Stefan, additional, Brescia Morra, Vincenzo, additional, Brochet, Bruno, additional, Brola, Waldemar, additional, Brownstone, Paul Kenneth, additional, Brozman, Miroslav, additional, Brunet, Donald, additional, Buraga, Ioan, additional, Burnett, Margaret, additional, Buttmann, Mathias, additional, Butzkueven, Helmut, additional, Cahill, Jonathan, additional, Calkwood, Jonathan C, additional, Camu, William, additional, Cascione, Mark, additional, Castelnovo, Giovani, additional, Centonze, Diego, additional, Cerqueira, Joao, additional, Chan, Andrew, additional, Cimprichova, Andrea, additional, Cohan, Stanley, additional, Comi, Giancarlo, additional, Conway, Jill, additional, Cooper, Joanna A, additional, Corboy, John, additional, Correale, Jorge, additional, Costell, Brian, additional, Cottrell, David A, additional, Coyle, Patricia K, additional, Craner, Matthew, additional, Cui, Liying, additional, Cunha, Luis, additional, Czlonkowska, Anna, additional, da Silva, Ana Martins, additional, de Sa, Joao, additional, de Seze, Jérôme, additional, Debouverie, Marc, additional, Debruyne, Jan, additional, Decoo, Danny, additional, Defer, Gilles, additional, Derfuss, Tobias, additional, Deri, Norma H, additional, Dihenia, Bhupesh, additional, Dioszeghy, Peter, additional, Donath, Vladimir, additional, Dubois, Benedicte, additional, Duddy, Martin, additional, Duquette, Pierre, additional, Edan, Gilles, additional, Efendi, Husnu, additional, Elias, Stanton, additional, Emrich, Peter J, additional, Estruch, Bonaventura Casanova, additional, Evdoshenko, Evgeniy P, additional, Faiss, Juergen, additional, Fedyanin, Alexander S, additional, Feneberg, Wolfgang, additional, Fermont, Jiske, additional, Fernandez, Oscar Fernandez, additional, Ferrer, Francisco Coret, additional, Fink, Katharina, additional, Ford, Helen, additional, Ford, Corey, additional, Francia, Ada, additional, Freedman, Mark, additional, Frishberg, Benjamin, additional, Galgani, Simonetta, additional, Garmany, George P, additional, Gehring, Klaus, additional, Gitt, Jeffrey, additional, Gobbi, Claudio, additional, Goldstick, Lawrence P, additional, Gonzalez, Rafael Arroyo, additional, Grandmaison, Francois, additional, Grigoriadis, Nikolaos, additional, Grigorova, Olga, additional, Grimaldi, Luigi Maria Edoardo, additional, Gross, Jeffrey, additional, Gross-Paju, Katrin, additional, Gudesblatt, Mark, additional, Guillaume, Daniel, additional, Haas, Judith, additional, Hancinova, Viera, additional, Hancu, Anca, additional, Hardiman, Orla, additional, Harmjanz, Arndt, additional, Heidenreich, Fedor R, additional, Hengstman, G J D, additional, Herbert, Joseph, additional, Herring, Mark, additional, Hodgkinson, Suzanne, additional, Hoffmann, Olaf M, additional, Hofmann, Werner E, additional, Honeycutt, William D, additional, Hua, Le Hanh, additional, Huang, Dehui, additional, Huang, Yining, additional, Huang, DeRen, additional, Hupperts, Raymond, additional, Imre, Piroska, additional, Jacobs, Alan Keith, additional, Jakab, Gabor, additional, Jasinska, Elzbieta, additional, Kaida, Kenichi, additional, Kalnina, Jolanta, additional, Kaprelyan, Ara, additional, Karelis, Guntis, additional, Karussis, Dimitrios, additional, Katz, Amos, additional, Khabirov, Farit A, additional, Khatri, Bhupendra, additional, Kimura, Takashi, additional, Kister, Ilya, additional, Kizlaitiene, Rasa, additional, Klimova, Eleonora, additional, Koehler, Juergen, additional, Komatineni, Aparna, additional, Kornhuber, Anselm, additional, Kovacs, Krisztina, additional, Koves, Agnes, additional, Kozubski, Wojciech, additional, Krastev, Georgi, additional, Krupp, Lauren B, additional, Kurca, Egon, additional, Lassek, Christoph, additional, Laureys, Guy, additional, Lee, Liesly, additional, Lensch, Eckart, additional, Leutmezer, Fritz, additional, Li, Hongzeng, additional, Linker, Ralf A, additional, Linnebank, Michael, additional, Liskova, Petra, additional, Llanera, Cristina, additional, Lu, Jiahong, additional, Lutterotti, Andreas, additional, Lycke, Jan, additional, Macdonell, Richard, additional, Maciejowski, Maciej, additional, Maeurer, Mathias, additional, Magzhanov, Rim V, additional, Maida, Eva-Maria, additional, Malciene, Lina, additional, Mao-Draayer, Yang, additional, Marfia, Girolama Alessandra, additional, Markowitz, Clyde, additional, Mastorodimos, Vasileios, additional, Matyas, Klotild, additional, Meca-Lallana, Jose, additional, Merino, Juan Antonio Garcia, additional, Mihetiu, Ioan Gheorghe, additional, Milanov, Ivan, additional, Miller, Aaron E, additional, Millers, Andrejs, additional, Mirabella, Massimiliano, additional, Mizuno, Masanori, additional, Montalban, Xavier, additional, Montoya, Lilina, additional, Mori, Masahiro, additional, Mueller, Stefanie, additional, Nakahara, Jin, additional, Nakatsuji, Yuji, additional, Newsome, Scott, additional, Nicholas, Richard, additional, Nielsen, A Scott, additional, Nikfekr, Esmaeil, additional, Nocentini, Ugo, additional, Nohara, Chiyoko, additional, Nomura, Kyoichi, additional, Odinak, Miroslav M, additional, Olsson, Tomas, additional, van Oosten, B W, additional, Oreja-Guevara, Celia, additional, Oschmann, Patrick, additional, Overell, James, additional, Pachner, Andrew, additional, Panczel, Gyula, additional, Pandolfo, Massimo, additional, Papeix, Caroline, additional, Patrucco, Liliana, additional, Pelletier, Jean, additional, Piedrabuena, Raul, additional, Pless, Misha, additional, Polzer, Udo, additional, Pozsegovits, Krisztian, additional, Rastenyte, Daiva, additional, Rauer, Sebastian, additional, Reifschneider, Gerd, additional, Rey, Roberto, additional, Rizvi, Syed A, additional, Robertson, Derrick, additional, Rodriguez, Jose Martinez, additional, Rog, David, additional, Roshanisefat, Homayoun, additional, Rowe, Vernon, additional, Rozsa, Csilla, additional, Rubin, Susan, additional, Rusek, Stanislaw, additional, Saccà, Francesco, additional, Saida, Takahiko, additional, Salgado, Antonio Vasco, additional, Sanchez, Victoria Eugenia Fernandez, additional, Sanders, Kalina, additional, Satori, Maria, additional, Sazonov, Denis V, additional, Scarpini, Elio Angelo, additional, Schlegel, Eugen, additional, Schluep, Myriam, additional, Schmidt, Stephan, additional, Scholz, Erich, additional, Schrijver, H M, additional, Schwab, Matthias, additional, Schwartz, Raymond, additional, Scott, James, additional, Selmaj, Krzysztof, additional, Shafer, Stuart, additional, Sharrack, Basil, additional, Shchukin, Ivan A, additional, Shimizu, Yuko, additional, Shotekov, Penko, additional, Siever, Arno, additional, Sigel, Karl-Otto, additional, Silliman, Scott, additional, Simo, Magdolna, additional, Simu, Mihaela, additional, Sinay, Vladimiro, additional, Siquier, Antonio Escartin, additional, Siva, Aksel, additional, Skoda, Ondrej, additional, Solomon, Andrew, additional, Stangel, Martin, additional, Stefoski, Dusan, additional, Steingo, Brian, additional, Stolyarov, Igor D, additional, Stourac, Pavel, additional, Strassburger-Krogias, Katrin, additional, Strauss, Erik, additional, Stuve, Olaf, additional, Tarnev, Ivaylo, additional, Tavernarakis, Antonios, additional, Tello, Cristina Ramo, additional, Terzi, Murat, additional, Ticha, Veronika, additional, Ticmeanu, Marina, additional, Tiel-Wilck, Klaus, additional, Toomsoo, Toomas, additional, Tubridy, Niall, additional, Tullman, Mark J, additional, Tumani, Hayrettin, additional, Turcani, Peter, additional, Turner, Ben, additional, Uccelli, Antonio, additional, Urtaza, Francisco Javier Olascoaga, additional, Vachova, Marta, additional, Valikovics, Attila, additional, Walter, Silke, additional, Van Wijmeersch, Bart, additional, Vanopdenbosch, Ludo, additional, Weber, Joerg R, additional, Weiss, Sara, additional, Weissert, Robert, additional, West, Timothy, additional, Wiendl, Heinz, additional, Wiertlewski, Sandrine, additional, Wildemann, Brigitte, additional, Willekens, Barbara, additional, Visser, L H, additional, Vorobeychik, Galina, additional, Xu, Xianhao, additional, Yamamura, Takashi, additional, Yang, Yi N, additional, Yelamos, Sergio Martinez, additional, Yeung, Michael, additional, Zacharias, Alan, additional, Zelkowitz, Marvin, additional, Zettl, Uwe, additional, Zhang, Meini, additional, Zhou, Hongyu, additional, Zieman, Ulf, additional, and Ziemssen, Tjalf, additional

Published
2018
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26. 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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29. 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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