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

Author

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

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

Author

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, Matthias, Boerner, Thomas, 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, Mathias, 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, Luis, Czlonkowska, Anna, da Silva, Ana Martins, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gilles, Derfuss, Tobias, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gilles, 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, Klaus, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francois, Grigoriadis, Nikolaos, 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, Guntis, Karussis, Dimitrios, Katz, Amos, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agnes, 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, Andreas, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathias, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileios, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrejs, 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, Tomas, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, James, 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, Matthias, Schwartz, Raymond, Scott, James, 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, Antonios, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klaus, Toomsoo, Toomas, 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, Vermersch, Patrick, 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, Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, and Dahlke, Frank

Published
2018
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4. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, Sifat, primary, Roos, Izanne, additional, Simpson-Yap, Steve, additional, Malpas, Charles, additional, Sánchez, Marina M, additional, Ozakbas, Serkan, additional, Horakova, Dana, additional, Havrdova, Eva K, additional, Patti, Francesco, additional, Alroughani, Raed, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Boz, Cavit, additional, Zakaria, Magd, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Weinstock-Guttman, Bianca, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Amato, Maria Pia, additional, Karabudak, Rana, additional, Grand’Maison, Francois, additional, Khoury, Samia J, additional, Grammond, Pierre, additional, Lechner-Scott, Jeannette, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Turkoglu, Recai, additional, Altintas, Ayse, additional, Maimone, Davide, additional, Kermode, Allan, additional, Shalaby, Nevin, additional, Pesch, Vincent V, additional, Butler, Ernest, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Mrabet, Saloua, additional, Gerlach, Oliver, additional, Soysal, Aysun, additional, Barnett, Michael, additional, Kuhle, Jens, additional, Hughes, Stella, additional, Sa, Maria J, additional, Hodgkinson, Suzanne, additional, Oreja-Guevara, Celia, additional, Ampapa, Radek, additional, Petersen, Thor, additional, Ramo-Tello, Cristina, additional, Spitaleri, Daniele, additional, McCombe, Pamela, additional, Taylor, Bruce, additional, Prevost, Julie, additional, Foschi, Matteo, additional, Slee, Mark, additional, McGuigan, Chris, additional, Laureys, Guy, additional, Hijfte, Liesbeth V, additional, de Gans, Koen, additional, Solaro, Claudio, additional, Oh, Jiwon, additional, Macdonell, Richard, additional, Aguera-Morales, Eduardo, additional, Singhal, Bhim, additional, Gray, Orla, additional, Garber, Justin, additional, Wijmeersch, Bart V, additional, Simu, Mihaela, additional, Castillo-Triviño, Tamara, additional, Sanchez-Menoyo, Jose L, additional, Khurana, Dheeraj, additional, Al-Asmi, Abdullah, additional, Al-Harbi, Talal, additional, Deri, Norma, additional, Fragoso, Yara, additional, Lalive, Patrice H, additional, Sinnige, L G F, additional, Shaw, Cameron, additional, Shuey, Neil, additional, Csepany, Tunde, additional, Sempere, Angel P, additional, Moore, Fraser, additional, Decoo, Danny, additional, Willekens, Barbara, additional, Gobbi, Claudio, additional, Massey, Jennifer, additional, Hardy, Todd, additional, Parratt, John, additional, and Kalincik, Tomas, additional

Published
2023
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5. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Daruwalla, Cyrus, primary, Shaygannejad, Vahid, additional, Ozakbas, Serkan, additional, Havrdova, Eva Kubala, additional, Horakova, Dana, additional, Alroughani, Raed, additional, Boz, Cavit, additional, Patti, Francesco, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Eichau, Sara, additional, Girard, Marc, additional, Prat, Alexandre, additional, Duquette, Pierre, additional, Yamout, Bassem, additional, Khoury, Samia J, additional, Sajedi, Seyed Aidin, additional, Turkoglu, Recai, additional, Altintas, Ayse, additional, Skibina, Olga, additional, Buzzard, Katherine, additional, Grammond, Pierre, additional, Karabudak, Rana, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Maimone, Davide, additional, Lechner-Scott, Jeannette, additional, Soysal, Aysun, additional, John, Nevin, additional, Prevost, Julie, additional, Spitaleri, Daniele, additional, Ramo-Tello, Cristina, additional, Gerlach, Oliver, additional, Iuliano, Gerardo, additional, Foschi, Matteo, additional, Ampapa, Radek, additional, van Pesch, Vincent, additional, Barnett, Michael, additional, Shalaby, Nevin, additional, D’hooghe, Marie, additional, Kuhle, Jens, additional, Sa, Maria Jose, additional, Fabis-Pedrini, Marzena, additional, Kermode, Allan, additional, Mrabet, Saloua, additional, Gouider, Riadh, additional, Hodgkinson, Suzanne, additional, Laureys, Guy, additional, Van Hijfte, Liesbeth, additional, Macdonell, Richard, additional, Oreja-Guevara, Celia, additional, Cristiano, Edgardo, additional, McCombe, Pamela, additional, Sanchez-Menoyo, Jose Luis, additional, Singhal, Bhim, additional, Blanco, Yolanda, additional, Hughes, Stella, additional, Garber, Justin, additional, Solaro, Claudio, additional, McGuigan, Chris, additional, Taylor, Bruce, additional, de Gans, Koen, additional, Habek, Mario, additional, Al-Asmi, Abdullah, additional, Mihaela, Simu, additional, Castillo Triviño, Tamara, additional, Al-Harbi, Talal, additional, Rojas, Juan Ignacio, additional, Gray, Orla, additional, Khurana, Dheeraj, additional, Van Wijmeersch, Bart, additional, Grigoriadis, Nikolaos, additional, Inshasi, Jihad, additional, Oh, Jiwon, additional, Aguera-Morales, Eduardo, additional, Fragoso, Yara, additional, Moore, Fraser, additional, Shaw, Cameron, additional, Baghbanian, Seyed Mohammad, additional, Shuey, Neil, additional, Willekens, Barbara, additional, Hardy, Todd A, additional, Decoo, Danny, additional, sempere, Angel Perez, additional, Field, Deborah, additional, Wynford-Thomas, Ray, additional, Cunniffe, Nick G, additional, Roos, Izanne, additional, Malpas, Charles B, additional, Coles, Alasdair J, additional, Kalincik, Tomas, additional, and Brown, J William L, additional

Published
2023
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6. Comparative effectiveness of autologous hematopoietic stem cell transplant vs Fingolimod, Natalizumab, and Ocrelizumab in highly active relapsing-remitting multiple sclerosis

Author

Kalincik, Tomas, Sharmin, Sifat, Roos, Izanne, Freedman, Mark S., Atkins, Harold, Burman, Joachim, Massey, Jennifer, Sutton, Ian, Withers, Barbara, Macdonell, Richard, Grigg, Andrew, Torkildsen, Øivind, Bo, Lars, Lehmann, Anne Kristine, Havrdova, Eva Kubala, Krasulova, Eva, Trněný, Marek, Kozak, Tomas, van der Walt, Anneke, Butzkueven, Helmut, McCombe, Pamela, Skibina, Olga, Lechner-Scott, Jeannette, Willekens, Barbara, Cartechini, Elisabetta, Ozakbas, Serkan, Alroughani, Raed, Kuhle, Jens, Patti, Francesco, Duquette, Pierre, Lugaresi, Alessandra, Khoury, Samia J., Slee, Mark, Turkoglu, Recai, Hodgkinson, Suzanne, John, Nevin, Maimone, Davide, Sa, Maria Jose, van Pesch, Vincent, Gerlach, Oliver, Laureys, Guy, Van Hijfte, Liesbeth, Karabudak, Rana, Spitaleri, Daniele, Csepany, Tunde, Gouider, Riadh, Castillo-Triviño, Tamara, Taylor, Bruce, Sharrack, Basil, Snowden, John A., Horakova, Dana, Buzzard, Katherine, Terzi, Murat, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Barnett, Michael, Stewart, Grace, Onofrj, Marco, Izquierdo, Guillermo, Eichau, Sara, Grand'Maison, Francois, Prevost, Julie, Van Wijmeersch, Bart, Amato, Maria Pia, Shaygannejad, Vahid, Boz, Cavit, Bolaños, Ricardo Fernandez, Soysal, Aysun, Ramo-Tello, Cristina, Solaro, Claudio, Gobbi, Claudio, Cabrera-Gomez, Jose Antonio, Roullet, Etienne, Zwanikken, Cees, Den braber-Moerland, Leontien, Deri, Norma, Saladino, Maria Laura, Cristiano, Edgardo, Rojas, Juan Ignacio, Vrech, Carlos, Shaw, Cameron, Shuey, Neil, Boggild, Mike, Tan, Ik Lin, Hardy, Todd, Decoo, Danny, Moore, Fraser, Oh, Jiwon, Lalive, Patrice, Ampapa, Radek, Petersen, Thor, Oreja-Guevara, Celia, Perez Sempere, Angel, Dominguez, Jose Andres, Besora, Sarah, Hughes, Stella, Gray, Orla, Grigoriadis, Nikolaos, Piroska, Imre, Rozsa, Csilla, Kasa, Krisztian, Simo, Magdolna, Kovacs, Krisztina, Sas, Attila, Dobos, Eniko, Rajda, Cecilia, McGuigan, Chris, Mason, Deborah, Schepel, Jan, Alkhaboori, Jabir, Rio, Maria Edite, Mihaela, Simu, Al-Harbi, Talal, Altintas, Ayse, Kister, Ilya, Marriott, Mark, Kilpatrick, Trevor, King, John, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Taylor, Lisa, Diamanti, Matteo, Chisari, Clara, Toscano, Simona, Salvatore, Lo Fermo, Larochelle, Catherine, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hupperts, Raymond, Olascoaga, Javier, Saiz, Albert, Zivadinov, Robert, Benedict, Ralph, Verheul, Freek, Fabis-Pedrini, Marzena, Mrabet, Saloua, Garber, Justin, Sanchez-Menoyo, Jose Luis, Aguera-Morales, Eduardo, Blanco, Yolanda, Al-Asmi, Abdullah, Weinstock-Guttman, Bianca, Fragoso, Yara, de Gans, Koen, and Kermode, Allan

Subjects
Human medicine
Abstract

you are agreeing to our Cookie Policy | Continue JAMA Network HomeJAMA Neurology This Issue Views 2,357 Citations 0 60 Full Text Share Comment Original Investigation May 15, 2023 Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis Tomas Kalincik, MD, PhD1,2; Sifat Sharmin, PhD1,2; Izanne Roos, MBChB, PhD1,2; Mark S. Freedman, MD3; Harold Atkins, MD4; Joachim Burman, MD, PhD5; Jennifer Massey, MBBS, PhD6,7; Ian Sutton, MBBS, PhD6,8; Barbara Withers, MD, PhD7,9; Richard Macdonell, MD, PhD10,11; Andrew Grigg, MD, PhD11,12; Øivind Torkildsen, MD, PhD13; Lars Bo, MD, PhD13; Anne Kristine Lehmann, MD, PhD14; Eva Kubala Havrdova, MD, PhD15; Eva Krasulova, MD, PhD15; Marek Trněný, MD, PhD16; Tomas Kozak, MD, PhD17; Anneke van der Walt, MBBS, PhD18,19; Helmut Butzkueven, MBBS, PhD18,19; Pamela McCombe, MBBS20,21; Olga Skibina, MBBS18,22,23; Jeannette Lechner-Scott, MD, PhD24,25; Barbara Willekens, MD, PhD26,27; Elisabetta Cartechini, MD28; Serkan Ozakbas, MD29; Raed Alroughani, MD30; Jens Kuhle, MD, PhD31; Francesco Patti, MD32,33; Pierre Duquette, MD34; Alessandra Lugaresi, MD, PhD35,36; Samia J. Khoury, MD, PhD37; Mark Slee, MD, PhD38; Recai Turkoglu, MD39; Suzanne Hodgkinson, MD40; Nevin John, MD, PhD41,42; Davide Maimone, MD43; Maria Jose Sa, MD44; Vincent van Pesch, MD, PhD45,46; Oliver Gerlach, MD, PhD47,48; Guy Laureys, MD49; Liesbeth Van Hijfte, MD49; Rana Karabudak, MD50; Daniele Spitaleri, MD51; Tunde Csepany, MD, PhD52; Riadh Gouider, MD53,54; Tamara Castillo-Triviño, MD55; Bruce Taylor, MD, PhD56,57; Basil Sharrack, MD, PhD58; John A. Snowden, MD, PhD59; and the MSBase Study Group Collaborators; and the MSBase Study Group Authors Author Affiliations JAMA Neurol. 2023;80(7):702-713. doi:10.1001/jamaneurol.2023.1184 editorial comment iconEditorial Comment Key Points Question What is the comparative effectiveness of autologous hematopoietic stem cell transplant (AHSCT) vs individual most potent disease-modifying therapies for relapsing-remitting multiple sclerosis (MS), such as natalizumab or ocrelizumab? Findings In this observational comparative effectiveness study of 4915 individuals using a composite cohort from specialized MS centers and the MSBase international registry, the effectiveness of AHSCT was compared with 1 medium-efficacy and 2 high-efficacy disease-modifying therapies (fingolimod, natalizumab, and ocrelizumab) in patients with relapsing-remitting MS, high frequency of relapses, and moderate disability. Over 5 years, AHSCT was associated with substantially lower relapse rate than fingolimod and marginally lower relapse rate than natalizumab and was also associated with a higher rate of recovery from disability compared with fingolimod and natalizumab, but no evidence of difference in clinical outcomes between AHSCT and ocrelizumab was found at 3-year follow-up. Meaning The results indicate that in relapsing-remitting MS, the clinical effectiveness of AHSCT is considerably superior to fingolimod and marginally superior to natalizumab. Abstract Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.

Published
2023

7. sj-docx-1-msj-10.1177_13524585231151951 – Supplemental material for Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Daruwalla, Cyrus, Shaygannejad, Vahid, Ozakbas, Serkan, Havrdova, Eva Kubala, Horakova, Dana, Alroughani, Raed, Boz, Cavit, Patti, Francesco, Onofrj, Marco, Lugaresi, Alessandra, Eichau, Sara, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Yamout, Bassem, Khoury, Samia J, Sajedi, Seyed Aidin, Turkoglu, Recai, Altintas, Ayse, Skibina, Olga, Buzzard, Katherine, Grammond, Pierre, Karabudak, Rana, van der Walt, Anneke, Butzkueven, Helmut, Maimone, Davide, Lechner-Scott, Jeannette, Soysal, Aysun, John, Nevin, Prevost, Julie, Spitaleri, Daniele, Ramo-Tello, Cristina, Gerlach, Oliver, Iuliano, Gerardo, Foschi, Matteo, Ampapa, Radek, van Pesch, Vincent, Barnett, Michael, Shalaby, Nevin, D’hooghe, Marie, Kuhle, Jens, Sa, Maria Jose, Fabis-Pedrini, Marzena, Kermode, Allan, Mrabet, Saloua, Gouider, Riadh, Hodgkinson, Suzanne, Laureys, Guy, Van Hijfte, Liesbeth, Macdonell, Richard, Oreja-Guevara, Celia, Cristiano, Edgardo, McCombe, Pamela, Sanchez-Menoyo, Jose Luis, Singhal, Bhim, Blanco, Yolanda, Hughes, Stella, Garber, Justin, Solaro, Claudio, McGuigan, Chris, Taylor, Bruce, de Gans, Koen, Habek, Mario, Al-Asmi, Abdullah, Mihaela, Simu, Castillo Triviño, Tamara, Al-Harbi, Talal, Rojas, Juan Ignacio, Gray, Orla, Khurana, Dheeraj, Van Wijmeersch, Bart, Grigoriadis, Nikolaos, Inshasi, Jihad, Oh, Jiwon, Aguera-Morales, Eduardo, Fragoso, Yara, Moore, Fraser, Shaw, Cameron, Baghbanian, Seyed Mohammad, Shuey, Neil, Willekens, Barbara, Hardy, Todd A, Decoo, Danny, sempere, Angel Perez, Field, Deborah, Wynford-Thomas, Ray, Cunniffe, Nick G, Roos, Izanne, Malpas, Charles B, Coles, Alasdair J, Kalincik, Tomas, and Brown, J William L

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_13524585231151951 for Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis by Cyrus Daruwalla, Vahid Shaygannejad, Serkan Ozakbas, Eva Kubala Havrdova, Dana Horakova, Raed Alroughani, Cavit Boz, Francesco Patti, Marco Onofrj, Alessandra Lugaresi, Sara Eichau, Marc Girard, Alexandre Prat, Pierre Duquette, Bassem Yamout, Samia J Khoury, Seyed Aidin Sajedi, Recai Turkoglu, Ayse Altintas, Olga Skibina, Katherine Buzzard, Pierre Grammond, Rana Karabudak, Anneke van der Walt, Helmut Butzkueven, Davide Maimone, Jeannette Lechner-Scott, Aysun Soysal, Nevin John, Julie Prevost, Daniele Spitaleri, Cristina Ramo-Tello, Oliver Gerlach, Gerardo Iuliano, Matteo Foschi, Radek Ampapa, Vincent van Pesch, Michael Barnett, Nevin Shalaby, Marie D’hooghe, Jens Kuhle, Maria Jose Sa, Marzena Fabis-Pedrini, Allan Kermode, Saloua Mrabet, Riadh Gouider, Suzanne Hodgkinson, Guy Laureys, Liesbeth Van Hijfte, Richard Macdonell, Celia Oreja-Guevara, Edgardo Cristiano, Pamela McCombe, Jose Luis Sanchez-Menoyo, Bhim Singhal, Yolanda Blanco, Stella Hughes, Justin Garber, Claudio Solaro, Chris McGuigan, Bruce Taylor, Koen de Gans, Mario Habek, Abdullah Al-Asmi, Simu Mihaela, Tamara Castillo Triviño, Talal Al-Harbi, Juan Ignacio Rojas, Orla Gray, Dheeraj Khurana, Bart Van Wijmeersch, Nikolaos Grigoriadis, Jihad Inshasi, Jiwon Oh, Eduardo Aguera-Morales, Yara Fragoso, Fraser Moore, Cameron Shaw, Seyed Mohammad Baghbanian, Neil Shuey, Barbara Willekens, Todd A Hardy, Danny Decoo, Angel Perez sempere, Deborah Field, Ray Wynford-Thomas, Nick G Cunniffe, Izanne Roos, Charles B Malpas, Alasdair J Coles, Tomas Kalincik and J William L Brown in Multiple Sclerosis Journal

Published
2023
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8. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Sharmin, Sifat, Roos, Izanne, Simpson-Yap, Steve, Malpas, Charles, Sánchez, Marina M, Ozakbas, Serkan, Horakova, Dana, Havrdova, Eva K, Patti, Francesco, Alroughani, Raed, Izquierdo, Guillermo, Eichau, Sara, Boz, Cavit, Zakaria, Magd, Onofrj, Marco, Lugaresi, Alessandra, Weinstock-Guttman, Bianca, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Terzi, Murat, Amato, Maria Pia, Karabudak, Rana, Grand'Maison, Francois, Khoury, Samia J, Grammond, Pierre, Lechner-Scott, Jeannette, Buzzard, Katherine, Skibina, Olga, van der Walt, Anneke, Butzkueven, Helmut, Turkoglu, Recai, Altintas, Ayse, Maimone, Davide, Kermode, Allan, Shalaby, Nevin, Pesch, Vincent V, Butler, Ernest, Sidhom, Youssef, Gouider, Riadh, Mrabet, Saloua, Gerlach, Oliver, Soysal, Aysun, Barnett, Michael, Kuhle, Jens, Hughes, Stella, Maria J, Sa, Hodgkinson, Suzanne, Oreja-Guevara, Celia, Ampapa, Radek, Petersen, Thor, Ramo-Tello, Cristina, Spitaleri, Daniele, Mccombe, Pamela, Taylor, Bruce, Prevost, Julie, Foschi, Matteo, Slee, Mark, Mcguigan, Chris, Laureys, Guy, Hijfte, Liesbeth V, de Gans, Koen, Solaro, Claudio, Jiwon, Oh, Macdonell, Richard, Aguera-Morales, Eduardo, Singhal, Bhim, Gray, Orla, Garber, Justin, Wijmeersch, Bart V, Simu, Mihaela, Triviño, Tamara C, Sanchez-Menoyo, Jose L, Khurana, Dheeraj, Al-Asmi, Abdullah, Al-Harbi, Talal, Deri, Norma, Fragoso, Yara, Lalive, Patrice H, Sinnige, L G F, Shaw, Cameron, Shuey, Neil, Csepany, Tunde, Sempere, Angel P, Moore, Fraser, Decoo, Danny, Willekens, Barbara, Gobbi, Claudio, Massey, Jennifer, Hardy, Todd, Parratt, John, and Kalincik, Tomas

Subjects
secondary progressive multiple sclerosis, health expenditure, disease-modifying therapy, geography, latitude
Published
2023

9. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Rojas, Juan Ignacio, Gray, Orla, Khurana, Dheeraj, Van Wijmeersch, Bart, Grigoriadis, Nikolaos, Inshasi, Jihad, Oh, Jiwon, Aguera-Morales, Eduardo, Fragoso, Yara, Moore, Fraser, Shaw, Cameron, Baghbanian, Seyed Mohammad, Shuey, Neil, Willekens, Barbara, Hardy, Todd A., Decoo, Danny, Sempere, Angel Perez, Field, Deborah, Wynford-Thomas, Ray, Cunniffe, Nick G., Roos, Izanne, Malpas, Charles B., Coles, Alasdair J., Kalincik, Tomas, Brown, J. William L., MSBase Study Grp, MSBase Study Grp, Shaygannejad, Vahid, Daruwalla, Cyrus, ÖZAKBAŞ, SERKAN, Havrdova, Eva Kubala, Horakova, Dana, Alroughani, Raed, BOZ, CAVİT, Patti, Francesco, Onofrj, Marco, Lugaresi, Alessandra, Eichau, Sara, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Yamout, Bassem, Khoury, Samia J., Sajedi, Seyed Aidin, Turkoglu, Recai, Altintas, Ayse, Skibina, Olga, Buzzard, Katherine, Grammond, Pierre, Karabudak, Rana, van der Walt, Anneke, Butzkueven, Helmut, Maimone, Davide, Lechner-Scott, Jeannette, Soysal, Aysun, John, Nevin, Prevost, Julie, Spitaleri, Daniele, Ramo-Tello, Cristina, Gerlach, Oliver, Iuliano, Gerardo, Foschi, Matteo, Ampapa, Radek, van Pesch, Vincent, Barnett, Michael, Shalaby, Nevin, D'hooghe, Marie, Kuhle, Jens, Sa, Maria Jose, Fabis-Pedrini, Marzena, Kermode, Allan, Mrabet, Saloua, Gouider, Riadh, Hodgkinson, Suzanne, Laureys, Guy, Van Hijfte, Liesbeth, Macdonell, Richard, Oreja-Guevara, Celia, Cristiano, Edgardo, McCombe, Pamela, Sanchez-Menoyo, Jose Luis, Singhal, Bhim, Blanco, Yolanda, Hughes, Stella, Garber, Justin, Solaro, Claudio, McGuigan, Chris, Taylor, Bruce, de Gans, Koen, Habek, Mario, Al-Asmi, Abdullah, Mihaela, Simu, Castillo Trivino, Tamara, Al-Harbi, Talal, MSBase Study Group, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Faculty of Medicine and Pharmacy, Daruwalla, Cyrus [0000-0002-2329-5329], Shaygannejad, Vahid [0000-0001-5511-509X], Horakova, Dana [0000-0003-1915-0036], Alroughani, Raed [0000-0001-5436-5804], Patti, Francesco [0000-0002-6923-0846], Lugaresi, Alessandra [0000-0003-2902-5589], Eichau, Sara [0000-0001-9159-3128], Duquette, Pierre [0000-0001-7231-1754], Sajedi, Seyed Aidin [0000-0002-6704-9787], van der Walt, Anneke [0000-0002-4278-7003], Lechner-Scott, Jeannette [0000-0002-3850-447X], Barnett, Michael [0000-0002-2156-8864], Oreja-Guevara, Celia [0000-0002-9221-5716], Habek, Mario [0000-0002-3360-1748], Castillo Triviño, Tamara [0000-0002-9249-3185], Inshasi, Jihad [0000-0001-5892-751X], Oh, Jiwon [0000-0001-5519-6088], Fragoso, Yara [0000-0001-8726-089X], Baghbanian, Seyed Mohammad [0000-0002-8138-7504], Hardy, Todd A [0000-0003-4145-3172], Decoo, Danny [0000-0001-7689-3114], Roos, Izanne [0000-0003-0371-3666], Kalincik, Tomas [0000-0003-3778-1376], Brown, J William L [0000-0002-7737-5834], Apollo - University of Cambridge Repository, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Neuroscience(all), Multiple sclerosis, prognosis, multiple sclerosis, Prognosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Medicine and Health Sciences, Humans, Human medicine, Neurology (clinical)
Abstract

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Published
2023
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10. Machine-learning-based prediction of disability progression in multiple sclerosis: an observational, international, multi-center study

Author

De Brouwer, Edward, primary, Becker, Thijs, additional, Werthen-Brabants, Lorin, additional, Dewulf, Pieter, additional, Iliadis, Dimitrios, additional, Dekeyser, Cathérine, additional, Laureys, Guy, additional, Van Wijmeersch, Bart, additional, Popescu, Veronica, additional, Dhaene, Tom, additional, Deschrijver, Dirk, additional, Waegeman, Willem, additional, De Baets, Bernard, additional, Stock, Michiel, additional, Horakova, Dana, additional, Patti, Francesco, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Girard, Marc, additional, Prat, Alexandre, additional, Lugaresi, Alessandra, additional, Grammond, Pierre, additional, Kalincik, Tomas, additional, Alroughani, Raed, additional, Grand’Maison, Francois, additional, Skibina, Olga, additional, Terzi, Murat, additional, Lechner-Scott, Jeannette, additional, Gerlach, Oliver, additional, Khoury, Samia J., additional, Cartechini, Elisabetta, additional, Van Pesch, Vincent, additional, Sa, Maria Jose, additional, Weinstock-Guttman, Bianca, additional, Blanco, Yolanda, additional, Ampapa, Radek, additional, Spitaleri, Daniele, additional, Solaro, Claudio, additional, Maimone, Davide, additional, Soysal, Aysun, additional, Iuliano, Gerardo, additional, Gouider, Riadh, additional, Castillo-Triviño, Tamara, additional, Sanchez-Menoyo, Jose Luis, additional, van der Walt, Anneke, additional, Oh, Jiwon, additional, Aguera-Morales, Eduardo, additional, Altintas, Ayse, additional, Al-Asmi, Abdullah, additional, de Gans, Koen, additional, Fragoso, Yara, additional, Csepany, Tunde, additional, Hodgkinson, Suzanne, additional, Deri, Norma, additional, Al-Harbi, Talal, additional, Taylor, Bruce, additional, Gray, Orla, additional, Lalive, Patrice, additional, Rozsa, Csilla, additional, McGuigan, Chris, additional, Kermode, Allan, additional, Perez sempere, Angel, additional, Mihaela, Simu, additional, Simo, Magdolna, additional, Hardy, Todd, additional, Decoo, Danny, additional, Hughes, Stella, additional, Grigoriadis, Nikolaos, additional, Sas, Attila, additional, Vella, Norbert, additional, Moreau, Yves, additional, and Peeters, Liesbet, additional

Published
2022
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12. MSJ881994__Appendix_2 – Supplemental material for Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

Author

Zhou, Yuan, Claflin, Suzi B, Stankovich, Jim, Mei, Ingrid Van Der, Simpson, Steve, Roxburgh, Richard H, Kalincik, Tomas, Blizzard, Leigh, Lugaresi, Alessandra, Alroughani, Raed, Sajedi, Seyed Aidin, Butzkueven, Helmut, Pucci, Eugenio, Spitaleri, Daniele LA, Granella, Franco, Cristiano, Edgardo, Yamout, Bassem, Hughes, Stella, Gouider, Riadh, Menoyo, José Luis Sánchez, Olascoaga, Javier, McGuigan, Chris, Shaw, Cameron, Kermode, Allan G, Krisztian Kasa, Al-Harbi, Talal, Ayse Altintas, Laureys, Guy, Fragoso, Yara, Hardy, Todd A, Tunde Csepany, Carmen-Adella Sirbu, Decoo, Danny, Sas, Attila, Alvarez-Cermeño, Jose C, Kotkata, Karim, Millán-Pascual, Jorge, and Taylor, Bruce V

Subjects
FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, MSJ881994__Appendix_2 for Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype by Yuan Zhou, Suzi B Claflin, Jim Stankovich, Ingrid van der Mei, Steve Simpson, Richard H Roxburgh, Tomas Kalincik, Leigh Blizzard, Alessandra Lugaresi, Raed Alroughani, Seyed Aidin Sajedi, Helmut Butzkueven, Eugenio Pucci, Daniele LA Spitaleri, Franco Granella, Edgardo Cristiano, Bassem Yamout, Stella Hughes, Riadh Gouider, José Luis Sánchez Menoyo, Javier Olascoaga, Chris McGuigan, Cameron Shaw, Allan G Kermode, Krisztian Kasa, Talal Al-Harbi, Ayse Altintas, Guy Laureys, Yara Fragoso, Todd A Hardy, Tunde Csepany, Carmen-Adella Sirbu, Danny Decoo, Attila Sas, Jose C Alvarez-Cermeño, Karim Kotkata, Jorge Millán-Pascual and Bruce V Taylor in Multiple Sclerosis Journal

Published
2019
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15. Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

Author

Van Hijfte, Liesbeth, Cambron, Melissa, Capron, Brigitte, Dachy, Bernard, Decoo, Danny, Dive, Dominique, Dubois, Bénédicte, Sankari, Souraya El, London, Frederic, Perrotta, Gaetano, Popescu, Veronica, Van Pesch, Vincent, Van Wijmeersch, Bart, Willekens, Barbara, and Laureys, Guy

Abstract

• MS nurses (MSN) and multidisciplinary teams (MDT) may increase MS care quality. • Disparities in MSN/MDT support remain in an accessible health care system. • Building consensus on care quality standards for MSN and MDT in MS is advised. • Recognition and reimbursement of MSN/MDT is needed. Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p =.015), spasticity (p =.042) and gait treatment (p =.035), but also more physiotherapy (p =.004), driver's license adjustment (p <.001) and a higher employment rate (p =.004). MDT access was associated with more frequent symptomatic bladder treatment (p =.047), higher physiotherapy rate (p <.001), higher work- (p=.002), insurance- (p <.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p <.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

Author

Zhou, Yuan, primary, Claflin, Suzi B, additional, Stankovich, Jim, additional, van der Mei, Ingrid, additional, Simpson, Steve, additional, Roxburgh, Richard H, additional, Kalincik, Tomas, additional, Blizzard, Leigh, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Sajedi, Seyed Aidin, additional, Butzkueven, Helmut, additional, Pucci, Eugenio, additional, Spitaleri, Daniele LA, additional, Granella, Franco, additional, Cristiano, Edgardo, additional, Yamout, Bassem, additional, Hughes, Stella, additional, Gouider, Riadh, additional, Sánchez Menoyo, José Luis, additional, Olascoaga, Javier, additional, McGuigan, Chris, additional, Shaw, Cameron, additional, Kermode, Allan G, additional, Kasa, Krisztian, additional, Al-Harbi, Talal, additional, Altintas, Ayse, additional, Laureys, Guy, additional, Fragoso, Yara, additional, Hardy, Todd A, additional, Csepany, Tunde, additional, Sirbu, Carmen-Adella, additional, Decoo, Danny, additional, Sas, Attila, additional, Alvarez-Cermeño, Jose C, additional, Kotkata, Karim, additional, Millán-Pascual, Jorge, additional, and Taylor, Bruce V, additional

Published
2019
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17. Improving fatigue in multiple sclerosis by smartphone-supported energy management: The MS TeleCoach feasibility study

Author

D'hooghe, Marie Beatrice, Penner, Iris Katharina, Nagels, Guy, Van Gassen, Geert, Kos, Daphne, Bouquiaux, Olivier, Cambron, Melissa, Decoo, Danny, Lysandropoulos, Andreas, Van Wijmeersch, Bart, Willekens, Barbara, D'hooghe, Marie Beatrice, Penner, Iris Katharina, Nagels, Guy, Van Gassen, Geert, Kos, Daphne, Bouquiaux, Olivier, Cambron, Melissa, Decoo, Danny, Lysandropoulos, Andreas, Van Wijmeersch, Bart, and Willekens, Barbara

Abstract

Background: Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period. The goal of the MS TeleCoach, conceived as a combination of monitoring, self-management and motivational messages, is to enhance levels of physical activity thereby improving fatigue in pwMS in an accessible and interactive way, reinforcing self-management of patients. Methods: We conducted a prospective, open-label feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status Scale ≤ 4 and moderate to severe fatigue as measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess the baseline activity level per patient, the target number of activity counts was gradually increased over the 12-week period through telecoaching. The primary efficacy outcome was change in FSMC total score from baseline to study end. A subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire, to evaluate the satisfaction with the MS TeleCoach device and the experienced service. Results: Seventy-five patients were recruited from 16 centres in Belgium, of which 57 patients (76%) completed the study. FSMC total score (p = 0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively) decreased from baseline to week 12, indicating an improvement in fatigue. One third of participants with severe fatigue changed to a lower FSMC category for both FSMC total score and subscores. The post-study evaluation of patient satisfaction showed that the intervention was well accepted and that patients were very satisfied with the quality of the professional, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

18. 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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19. 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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20. Treatment adherence in multiple sclerosis: a survey of Belgian neurologists

Author

Decoo,Danny, Vokaer,Mathieu, Decoo,Danny, and Vokaer,Mathieu

Abstract

Danny Decoo,1 Mathieu Vokaer2 1Department of Neurology and Neurorehab, AZ Alma, Sijsele, Belgium; 2Multiple Sclerosis Clinic, Edith Cavell Hospital, CHIREC group, Brussels, Belgium Background: Poor treatment adherence is common among patients with multiple sclerosis (MS). This survey evaluated neurologists’ perception of treatment adherence among MS patients.Materials and methods: This questionnaire-based survey of Belgian neurologists treating MS patients was conducted between June and July 2014. Face-to-face interviews with the neurologists were based on a semistructured questionnaire containing questions regarding the perception of the treatment-adherence level.Results: A total of 41 neurologists participated in the survey. Of these, 88% indicated frequent discussions about treatment adherence as beneficial for treatment efficacy. The mean time spent on the treatment-adherence discussion during the initial consultation was 11 minutes, with 24% of doctors spending 5 minutes and 24% of doctors spending 10 minutes discussing this issue. The majority of neurologists (56%) perceived the adherence level in MS as good, and 12% perceived it as excellent. The majority of neurologists (64%) indicated intolerance as a main cause of poor adherence, and all neurologists reported insufficient efficacy as a consequence of nonadherence. The importance of adherence in the neurologists’ practice was evaluated on a scale of 1–10, with 1= “not very important” and 10= “very important”: 44% of doctors indicated a score of 10, and the mean score was 9.0.Conclusion: Belgian neurologists consider treatment adherence in MS as essential for the benefits of therapies. However, although neurologists are aware of the consequences of nonadherence, they generally spend limited time discussing the importance of treatment adherence with their patients. Keywords: multiple sclerosis, treatment adherence, physician survey

Published
2015

22. Association of interferon beta and inosine in relapsing-remitting multiple sclerosis (ASIIMS): a multi-centre, randomized, double-blind, placebo-con trolled phase II (proof of concept) trial in 157 patients

Author

Gonsette, Richard, Cindic, Christian, D'hooghe, Marie-Beatrice, Medaer, Robert, Michotte, Alex, De Deyn, Peter, Seeldrayers, P., Guillaume, Daniel, Metz, René, De Noordhout, Alain Maertens, Dupuis, M., Cras, Patrick, Decoo, Danny, Van Zandijcke, M., and Anatomy

Subjects
inosine, interferon, multiple sclerosis
Abstract

Neuronal and axonal loss occurs early in relapsing-remitting multiple sclerosis (RRMS) and is mediated by inflammatory processes as well as by oxidative stress and excitotoxicity. Effective anti-inflammatory drugs are available but the development of neuroprotective agents remains a challenge. Experimental and clinical observations suggest that uric acid (UA), a natural antioxidant, has a neuroprotective effect in EAE and possibly in MS. Oral administration of inosine, a precursor of UA, increases serum and CSF UA levels in MS patients and is well tolerated. Combination therapy with an anti-inflammatory drug (IFN-Beta) and a potentially neuroprotective agent (inosine) might delay disability progression. Patients with RRMS who had been on IFN-Beta for at least 6 months at baseline were randomized to IFN? + inosine (n=79) or IFN-Beta + placebo (n=78) for 2 years. The two groups were not significantly different in terms of age (~37 years), disease duration (~6.2 years), mean EDSS (~2.3) and annual relapse rate (~0.8). The dose of inosine was adjusted to maintain serum UA levels in the range of asymptomatic hyperuricemia (females ?8mg/dL; males ?9mg/dL). Expanded Disability Status Scale (EDSS) and MSFC components were assessed every 3 months by a blinded evaluating physician. The primary end points were: percentage of patients with progression of disability (EDSS+1 confirmed at 3 months), time to sustained progression (Kaplan-Meier analysis) and mean EDSS. The combination of IFN-Beta and inosine was safe and well tolerated. Urinary lithiasis occurred in 3.8% of treated patients and 1.3% of controls. No change in blood pressure was noted in patients with induced asymptomatic hyperuricemia. At 24 months no significant differences were observed between the two groups in any of the primary end points. Combination therapy with IFN-Beta and inosine is not superior to IFN? monotherapy. Potential reasons will be discussed. Inosine effects might be masked by those of IFN? and the negative results of this combination therapy do not rule out a possible benefit of UA in naîve patients.

Published
2008

23. Long-term follow up of glatiramer acetate compassionate use in Belgium

Author

Sindic, Christian Jean Marie, Seeldrayers, Pierette, Vande Gaer, Luc, De Smet, Eric, Nagels, Guy, De Deyn, Peter Paul, Medaer, Robert, Guillaume, Daniel, D'hooghe, Marie Beatrice, Deville, Marlène, Decoo, Danny, Sadzot, Bernard, Van Landegem, William, Strauven, Theo, Pepin, J., Merckx, Henri, Caekebeke, Jo F V J., van der Tool, M.A. M.A., Sindic, Christian Jean Marie, Seeldrayers, Pierette, Vande Gaer, Luc, De Smet, Eric, Nagels, Guy, De Deyn, Peter Paul, Medaer, Robert, Guillaume, Daniel, D'hooghe, Marie Beatrice, Deville, Marlène, Decoo, Danny, Sadzot, Bernard, Van Landegem, William, Strauven, Theo, Pepin, J., Merckx, Henri, Caekebeke, Jo F V J., and van der Tool, M.A. M.A.

Abstract

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone®) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 263% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63 ;most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al. 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2005

31. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

Author

Montalban, Xavier, Hauser, Stephen L., Kappos, Ludwig, Arnold, Douglas L., Bar-Or, Amit, Comi, Giancarlo, Seze, Jérôme, Giovannoni, Gavin, Hartung, Hans-Peter, Hemmer, Bernhard, Lublin, Fred, Rammohan, Kottil W., Selmaj, Krzysztof, Traboulsee, Anthony, Sauter, Annette, Masterman, Donna, Fontoura, Paulo, Belachew, Shibeshih, Garren, Hideki, Mairon, Nicole, Chin, Peter, Wolinsky, Jerry S., Oratorio, Clinical Investigators, Reingold, Stephen C., Sandberg-Wollheim, Magnhild, Barkhof, Frederik, Dörner, Thomas, Evans, Scott, Mcfarland, Henry F., Steiner, Israel, Yaldizli, Özgür, D Souza, Marcus, Andelova, Michaela, Rust, Heiko, Sedal, Leslie, Taylor, Bruce, Assar, Hamid, Auff, Eduard, Berger, Thomas, Guger, Michael, Pilz, Georg, Wipfler, Peter, Bartholomé, Emmanuel, Decoo, Danny, Becker, Jefferson, Da Silva Filho, Irenio, Diniz, Denise, Gomes Neto, Antônio, Leon, Soniza, Haralanov, Lyubomir, Milanov, Ivan, Bar-Or, Amir, Freedman, Mark, Grand Maison, François, Marriott, James, O Connor, Paul, Selchen, Daniel, Yeung, Michael, Benesova, Yvonne, Krasulova, Eva, Vachova, Marta, Airas, Laura, Elovaara, Irina, Färkkilä, Markus, Korpela, Jaana, Sumelahti, Marja-Liisa, Brassat, David, Brochet, Bruno, Camu, William, Castelnovo, Giovanni, Clanet, Michel, Clavelou, Pierre, Debouverie, Marc, Defer, Giles, Gout, Olivier, Heinzlef, Olivier, Laplaud, David, Lebrun-Frenay, Christine, Papeix, Caroline, Pelletier, Jean, Tourbah, Ayman, Vermersch, Patrick, Vukusic, Sandra, Angstwurm, Klemens, Berghoff, Martin, Förch, Christian, Goebels, Norbert, Haas, Judith, Harms, Lutz, Kleiter, Ingo, Koehler, Jürgen, Lensch, Eckard, Limmroth, Volker, Meuth, Sven, Oschmann, Patrick, Platten, Michael, Then Bergh, Florian, Tumani, Hayrettin, Ziemann, Ulf, Ziemssen, Tjalf, Afradou, Theodora, Fakas, Nikolaos, Tsounis, Stefanos, Vlaikidis, Nikolaos, Jakab, Gábor, Komoly, Sámuel, Rózsa, Csilla, Sátori, Mária, Szabó, Gyöngyi, Vécsei, László, Achiron, Anat, Hellmann, Mark, Karni, Arnon, Karussis, Dimitrios, Milo, Ron, Shahien, Radi, Bertolotto, Antonio, Marrosu, Maria Giovanna, Uccelli, Antonio, Malciene, Lina, Rastenyte, Daiva, Sceponaviciute, Sigla, Castro Farfan, Freddy, Duriez Sotelo, Eduardo, Flores-Rivera, Jose, Reyes Morales, Sarug, Hintzen, Rogier, Hupperts, Raymond, Lynch, Christopher, Mossman, Stuart, Gulowsen Celius, Elisabeth, Gavidia Chucan, Jorge, Perez Villegas, Julio, Pretell Alva, Edwin, Bielecki, Dariusz, Brola, Waldemar, Kochanowicz, Jan, Maciejowski, Maciej, Stelmasiak, Zbigniew, Zbrojkiewicz, Janusz, Cunha, Luis, Gonçalves, José, Mendes, Irene, Sá, João, Salgado, Vasco, Silva, Ana, Balasa, Rodica, Manescu, Silviu, Panea, Cristina Aura, Simu, Mihaela Adriana, Yakupov, Eduard, Álvarez Cermeño, José, Álvarez Cermeño, Carlos, Arroyo, Rafael, Escartín Siquier, Antonio, Fernández, Oscar, Izquierdo Ayuso, Guillermo, Martinez Rodríguez, José Enrique, Fernandez Sanchez, Victoria, Olascoaga Urtaza, Francisco Javier, Meca, Virginia, Olascoaga, Javier, Oreja-Guevara, Celia, Perez Sempere, Angel, Prieto González, José María, Ramió Torrentá, Lluis, Rodríguez-Antigüeda, Alfredo, Saiz, Albert, Gobbi, Claudio, Kuhle, Jens, Galusha, Anatoliy, Goloborodko, Alla, Litovchenko, Tetyana, Moroz, Olena, Sergii Moskovko, Nehrych, Tetyana, Pashkovskyy, Valeriy, Shkolnyk, Valerii, Shulga, Olga, Sokolova, Larysa, Voloshyna, Nataliya, Brex, Peter, Constantinescu, Cris, Duddy, Martin, Schmierer, Klaus, Young, Carolyn, Agius, Mark, Ash, Paul, Bandari, Daniel, Belkin, Martin, Bernitsas, Evanthia, Bowen, James, Cahill, Jonathan, Carpenter, Adam, Carter, Jonathan, Cerghet, Mirela, Conway, Jill, Cooper, Joanna, Coyle, Patricia, Cross, Anne, Ford, Corey, Fox, Edward, Freedman, S. Mitchell, Frohman, Elliot, Gitt, Jeffrey, Gottesman, Malcolm, Gudesblatt, Mark, Hendin, Barry, Hutton, George, Klineova, Sylvia, Krupp, Lauren, Lynch, Sharon, Markowitz, Clyde, Mattson, David, Miller, Aaron, Miravalle, Augusto, Muley, Suraj, Nealon, Nancy, Pardo, Gabriel, Picone, Mary Ann, Racke, Michael, Rizvi, Syed, Rossman, Howard, Rowe, Vernon, Schulman, Alan, Shafer, Stuart, William, Sheremata, Stein, Lee, and Waubant, Emmanuelle

32. 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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33. Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related findings

Author

Versijpt, J., Van Laere, K.J., Dumont, F., Decoo, Danny, Vandecapelle, Marleen, Santens, Patrick, Goethals, Ingeborg, Audenaert, K., Slegers, G., Dierckx, Rudi A., and Korf, Jakob

Subjects
*SEROTONIN uptake inhibitors, *HEART
Abstract

Serotonin (5-HT) and more specifically the 5-HT2A receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimer’s disease (AD). The objective was to assess the 5-HT2A binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT2A receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT2A receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD. [Copyright &y& Elsevier]

Published
2003
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34. The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.

Author

Levitz D, Chao Foong Y, Sanfilippo P, Spelman T, Rath L, Roldan A, Lal A, Monif M, Jokubaitis V, Ozakbas S, Alroughani R, Boz C, Terzi M, Kalincik T, Blanco Y, Foschi M, Surcinelli A, Buzzard K, Skibina O, Laureys G, Van Hijfte L, Ramo-Tello C, Soysal A, Sanchez-Menoyo JL, Habek M, Cartechini E, Rojas JI, Karabudak R, Willekens B, Al-Harbi T, Fragoso Y, Castillo-Triviño T, Decoo D, Aragon de Vecino MC, Skromne E, Sirbu CA, Zhu C, Merlo D, Gresle M, Butzkueven H, and Van Der Walt A

Abstract

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort., Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort., Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years., Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed., Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection., Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS., (© The Author(s), 2024.)

Published
2024
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35. Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study.

Author

De Brouwer E, Becker T, Werthen-Brabants L, Dewulf P, Iliadis D, Dekeyser C, Laureys G, Van Wijmeersch B, Popescu V, Dhaene T, Deschrijver D, Waegeman W, De Baets B, Stock M, Horakova D, Patti F, Izquierdo G, Eichau S, Girard M, Prat A, Lugaresi A, Grammond P, Kalincik T, Alroughani R, Grand'Maison F, Skibina O, Terzi M, Lechner-Scott J, Gerlach O, Khoury SJ, Cartechini E, Van Pesch V, Sà MJ, Weinstock-Guttman B, Blanco Y, Ampapa R, Spitaleri D, Solaro C, Maimone D, Soysal A, Iuliano G, Gouider R, Castillo-Triviño T, Sánchez-Menoyo JL, Laureys G, van der Walt A, Oh J, Aguera-Morales E, Altintas A, Al-Asmi A, de Gans K, Fragoso Y, Csepany T, Hodgkinson S, Deri N, Al-Harbi T, Taylor B, Gray O, Lalive P, Rozsa C, McGuigan C, Kermode A, Sempere AP, Mihaela S, Simo M, Hardy T, Decoo D, Hughes S, Grigoriadis N, Sas A, Vella N, Moreau Y, and Peeters L

Abstract

Background: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking., Methods: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms&#95;benchmark, making this task an ideal benchmark for predicting disability progression in MS., Findings: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history., Conclusions: Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study., Competing Interests: The authors declare no competing non-financial interests but the following competing financial interests: - Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, as well as support for research activities from Biogen and Czech Minsitry of Education [project Progres Q27/LF1]. - Francesco Patti received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. He received research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association and University of Catania. - Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva. - Sara Eichau received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. - Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. - Alessandra Lugaresi has served as a Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche, Sanofi/ Genzyme and Teva Advisory Board Member. She received congress and travel/accommodation expense compensations or speaker honoraria from Biogen, Merck, Mylan, Novartis, Roche, Sanofi/Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institutions received research grants from Novartis and Sanofi Genzyme. - Pierre Grammond has served in advisory boards for Novartis, EMD Serono, Roche, Biogen idec, Sanofi Genzyme, Pendopharm and has received grant support from Genzyme and Roche, has received research grants for his institution from Biogen idec, Sanofi Genzyme, EMD Serono. - Tomas Kalincik served on scientific advisory boards for BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. - Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. - Francois Grand’Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals. - Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. - Jeannette Lechner-Scott travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis. - Samia J. Khoury received compensation for participation in the Novartis Maestro program. - Vincent van Pesch has received travel grants from Merck, Biogen, Sanofi, Bristol Myers Squibb, Almirall and Roche; his institution receives honoraria for consultancy and lectures and research grants from Roche, Biogen, Sanofi, Merck, Bristol Myers Squibb, Janssen, Almirall and Novartis Pharma. - Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion. - Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. - Claudio Solaro served on scientific advisory boards for Merck, Genzyme, Almirall, and Biogen; received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen, Merck, Genzyme and Teva. - Davide Maimone served on scientific advisory boards for Bayer, Biogen, Merck, Sanofi-Genzyme, Novartis, Roche, and Almirall; received honoraria and travel grants from Sanofi Genzyme, Novartis, Biogen, Merck, and Roche. - Gerardo Iuliano (retired - no PI successor but has approved ongoing use of data) had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva. - Bart Van Wijmeersch received research and travel grants, honoraria for MS-Expert advisor and Speaker fees from Bayer-Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche and Teva. - Tamara Castillo Triviño received speaking/consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. - Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Merck and Roche - Guy Laureys received travel and/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen. - Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche She has received speaker’s honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. - Jiwon Oh has received research funding from the MS Society of Canada, National MS Society, Brain Canada, Biogen, Roche, EMD Serono (an affiliate of Merck KGaA); and personal compensation for consulting or speaking from Alexion, Biogen, Celgene (BMS), EMD Serono (an affiliate of Merck KGaA), Novartis, Roche, and Sanofi-Genzyme. - Ayse Altintas received speaker honoraria from Merck, Alexion,; received travel and registration grants from Merck, Biogen - Gen Pharma, Roche, Sanofi-Genzyme. - Yara Fragoso received honoraria as a consultant on scientific advisory boards by Novartis, Teva, Roche and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, Roche and Merck. - Tunde Csepany received speaker honoraria/ conference travel support from Bayer Schering, Biogen, Merck, Novartis, Roche, Sanofi-Aventis and Teva. - Suzanne Hodgkinson received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering. - Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis. - Bruce Taylor received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. - Fraser Moore participated in clinical trials sponsored by EMD Serono and Novartis. - Orla Gray received honoraria as consultant on scientific advisory boards for Genzyme, Biogen, Merck, Roche and Novartis; has received travel grants from Biogen, Merck, Roche and Novartis; has participated in clinical trials by Biogen and Merck. - Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck and Bayer Schering. - Allan Kermode received speaker honoraria and scientific advisory board fees from Bayer, BioCSL, Biogen, Genzyme, Innate Immunotherapeutics, Merck, Novartis, Sanofi, Sanofi-Aventis, and Teva. - Magdolna Simo received speaker honoraria from Novartis, Biogen, Bayer Schering; congress/travel compensation from Teva, Biogen, Merck, Bayer Schering. - Todd Hardy has received speaking fees or received honoraria for serving on advisory boards for Biogen, Merck, Teva, Novartis, Roche, Bristol-Myers Squibb and Sanofi-Genzyme, is Co-Editor of Advances in Clinical Neurosciences and Rehabilitation, and serves on the editorial board of Journal of Neuroimmunology and Frontiers in Neurology. - Nikolaos Grigoriadis received honoraria, consultancy/lecture fees, travel support and research grants from Biogen Idec, Biologix, Novartis, TEVA, Bayer, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE, Cellgene, ELPEN and research grants from Hellenic Ministry of Development., (Copyright: © 2024 De Brouwer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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36. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

Author

Daruwalla C, Shaygannejad V, Ozakbas S, Havrdova EK, Horakova D, Alroughani R, Boz C, Patti F, Onofrj M, Lugaresi A, Eichau S, Girard M, Prat A, Duquette P, Yamout B, Khoury SJ, Sajedi SA, Turkoglu R, Altintas A, Skibina O, Buzzard K, Grammond P, Karabudak R, van der Walt A, Butzkueven H, Maimone D, Lechner-Scott J, Soysal A, John N, Prevost J, Spitaleri D, Ramo-Tello C, Gerlach O, Iuliano G, Foschi M, Ampapa R, van Pesch V, Barnett M, Shalaby N, D'hooghe M, Kuhle J, Sa MJ, Fabis-Pedrini M, Kermode A, Mrabet S, Gouider R, Hodgkinson S, Laureys G, Van Hijfte L, Macdonell R, Oreja-Guevara C, Cristiano E, McCombe P, Sanchez-Menoyo JL, Singhal B, Blanco Y, Hughes S, Garber J, Solaro C, McGuigan C, Taylor B, de Gans K, Habek M, Al-Asmi A, Mihaela S, Castillo Triviño T, Al-Harbi T, Rojas JI, Gray O, Khurana D, Van Wijmeersch B, Grigoriadis N, Inshasi J, Oh J, Aguera-Morales E, Fragoso Y, Moore F, Shaw C, Baghbanian SM, Shuey N, Willekens B, Hardy TA, Decoo D, Sempere AP, Field D, Wynford-Thomas R, Cunniffe NG, Roos I, Malpas CB, Coles AJ, Kalincik T, and Brown JWL

Subjects
Humans, Prognosis, Recurrence, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis
Abstract

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear., Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS., Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up., Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n  = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n  = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n  = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically., Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Published
2023
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37. Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

Author

Zhou Y, Claflin SB, Stankovich J, van der Mei I, Simpson S Jr, Roxburgh RH, Kalincik T, Blizzard L, Lugaresi A, Alroughani R, Sajedi SA, Butzkueven H, Pucci E, Spitaleri D, Granella F, Cristiano E, Yamout B, Hughes S, Gouider R, Sánchez Menoyo JL, Olascoaga J, McGuigan C, Shaw C, Kermode AG, Kasa K, Al-Harbi T, Altintas A, Laureys G, Fragoso Y, Hardy TA, Csepany T, Sirbu CA, Decoo D, Sas A, Alvarez-Cermeño JC, Kotkata K, Millán-Pascual J, and Taylor BV

Subjects
Disability Evaluation, Disease Progression, Female, Humans, Male, Phenotype, Recurrence, Severity of Illness Index, Multiple Sclerosis diagnosis, Multiple Sclerosis epidemiology
Abstract

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups., Objective: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets., Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis., Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( p  > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( p  < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex., Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Published
2020
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