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2. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease

Author

Phillips, Matthew C. L., Deprez, Laura M., Mortimer, Grace M. N., Murtagh, Deborah K. J., McCoy, Stacey, Mylchreest, Ruth, Gilbertson, Linda J., Clark, Karen M., Simpson, Patricia V., McManus, Eileen J., Oh, Jee-Eun, Yadavaraj, Satish, King, Vanessa M., Pillai, Avinesh, Romero-Ferrando, Beatriz, Brinkhuis, Martijn, Copeland, Bronwyn M., Samad, Shah, Liao, Shenyang, and Schepel, Jan A. C.

Published
2021
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3. 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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4. Comparative effectiveness in multiple sclerosis: A methodological comparison

Author

Roos, Izanne, primary, Diouf, Ibrahima, additional, Sharmin, Sifat, additional, Horakova, Dana, additional, Havrdova, Eva Kubala, additional, Patti, Francesco, additional, Shaygannejad, Vahid, additional, Ozakbas, Serkan, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Boz, Cavit, additional, Grand’Maison, Francois, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Grammond, Pierre, additional, Turkoglu, Recai, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, Yamou, Bassem, additional, Altintas, Ayse, additional, Gerlach, Oliver, additional, van Pesch, Vincent, additional, Blanco, Yolanda, additional, Maimone, Davide, additional, Lechner-Scott, Jeannette, additional, Bergamaschi, Roberto, additional, Karabudak, Rana, additional, McGuigan, Chris, additional, Cartechini, Elisabetta, additional, Barnett, Michael, additional, Hughes, Stella, additional, Sa, Maria José, additional, Solaro, Claudio, additional, Ramo-Tello, Cristina, additional, Hodgkinson, Suzanne, additional, Spitaleri, Daniele, additional, Soysal, Aysun, additional, Petersen, Thor, additional, Granella, Franco, additional, de Gans, Koen, additional, McCombe, Pamela, additional, Ampapa, Radek, additional, Van Wijmeersch, Bart, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Prevost, Julie, additional, Sanchez-Menoyo, Jose Luis, additional, Laureys, Guy, additional, Gouider, Riadh, additional, Castillo-Triviño, Tamara, additional, Gray, Orla, additional, Aguera-Morales, Eduardo, additional, Al-Asmi, Abdullah, additional, Shaw, Cameron, additional, Deri, Norma, additional, Al-Harbi, Talal, additional, Fragoso, Yara, additional, Csepany, Tunde, additional, Sempere, Angel Perez, additional, Trevino-Frenk, Irene, additional, Schepel, Jan, additional, Moore, Fraser, additional, Malpas, Charles, additional, and Kalincik, Tomas, additional

Published
2023
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5. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Diouf, Ibrahima, primary, Malpas, Charles B., additional, Sharmin, Sifat, additional, Roos, Izanne, additional, Horakova, Dana, additional, Havrdova, Eva Kubala, additional, Patti, Francesco, additional, Shaygannejad, Vahid, additional, Ozakbas, Serkan, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Boz, Cavit, additional, Grand'Maison, Francois, additional, Hamdy, Sherif, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Grammond, Pierre, additional, Turkoglu, Recai, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, Yamout, Bassem, additional, Altintas, Ayse, additional, Gerlach, Oliver, additional, van Pesch, Vincent, additional, Blanco, Yolanda, additional, Maimone, Davide, additional, Lechner‐Scott, Jeannette, additional, Bergamaschi, Roberto, additional, Karabudak, Rana, additional, Iuliano, Gerardo, additional, McGuigan, Chris, additional, Cartechini, Elisabetta, additional, Barnett, Michael, additional, Hughes, Stella, additional, Sa, Maria José, additional, Solaro, Claudio, additional, Kappos, Ludwig, additional, Ramo‐Tello, Cristina, additional, Cristiano, Edgardo, additional, Hodgkinson, Suzanne, additional, Spitaleri, Daniele, additional, Soysal, Aysun, additional, Petersen, Thor, additional, Slee, Mark, additional, Butler, Ernest, additional, Granella, Franco, additional, de Gans, Koen, additional, McCombe, Pamela, additional, Ampapa, Radek, additional, Van Wijmeersch, Bart, additional, van der Walt, Anneke, additional, Butzkueven, Helmut, additional, Prevost, Julie, additional, Sinnige, L. G. F., additional, Sanchez‐Menoyo, Jose Luis, additional, Vucic, Steve, additional, Laureys, Guy, additional, Van Hijfte, Liesbeth, additional, Khurana, Dheeraj, additional, Macdonell, Richard, additional, Gouider, Riadh, additional, Castillo‐Triviño, Tamara, additional, Gray, Orla, additional, Aguera‐Morales, Eduardo, additional, Al‐Asmi, Abdullah, additional, Shaw, Cameron, additional, Deri, Norma, additional, Al‐Harbi, Talal, additional, Fragoso, Yara, additional, Csepany, Tunde, additional, Perez Sempere, Angel, additional, Trevino‐Frenk, Irene, additional, Schepel, Jan, additional, Moore, Fraser, additional, and Kalincik, Tomas, additional

Published
2023
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6. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Diouf, Ibrahima; Malpas, Charles B.; Sharmin, Sifat; Roos, Izanne; Horakova, Dana; Havrdova, Eva Kubala; Patti, Francesco; Shaygannejad, Vahid; Ozakbas, Serkan; Izquierdo, Guillermo; Eichau, Sara; Onofrj, Marco; Lugaresi, Alessandra; Alroughani, Raed; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Terzi, Murat; Boz, Cavit; Grand'Maison, Francois; Hamdy, Sherif; Sola, Patrizia; Ferraro, Diana; Grammond, Pierre; Turkoglu, Recai; Buzzard, Katherine; Skibina, Olga; Yamout, Bassem; Gerlach, Oliver; van Pesch, Vincent; Blanco, Yolanda; Maimone, Davide; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Karabudak, Rana; Iuliano, Gerardo; McGuigan, Chris; Cartechini, Elisabetta; Barnett, Michael; Hughes, Stella; Sa, Maria Jose; Solaro, Claudio; Kappos, Ludwig; Ramo-Tello, Cristina; Cristiano, Edgardo; Hodgkinson, Suzanne; Spitaleri, Daniele; Soysal, Aysun; Petersen, Thor; Slee, Mark; Butler, Ernest; Granella, Franco; de Gans, Koen; McCombe, Pamela; Ampapa, Radek; Van Wijmeersch, Bart; van der Walt, Anneke; Butzkueven, Helmut; Prevost, Julie; Sinnige, L. G. F.; Sanchez-Menoyo, Jose Luis; Vucic, Steve; Laureys, Guy; Van Hijfte, Liesbeth; Khurana, Dheeraj; Macdonell, Richard; Gouider, Riadh; Castillo-Trivino, Tamara; Gray, Orla; Aguera-Morales, Eduardo; Al-Asmi, Abdullah; Shaw, Cameron; Deri, Norma; Al-Harbi, Talal; Fragoso, Yara; Csepany, Tunde; Sempere, Angel Perez; Trevino-Frenk, Irene; Schepel, Jan; Moore, Fraser; Kalincik, Tomas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Diouf, Ibrahima; Malpas, Charles B.; Sharmin, Sifat; Roos, Izanne; Horakova, Dana; Havrdova, Eva Kubala; Patti, Francesco; Shaygannejad, Vahid; Ozakbas, Serkan; Izquierdo, Guillermo; Eichau, Sara; Onofrj, Marco; Lugaresi, Alessandra; Alroughani, Raed; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Terzi, Murat; Boz, Cavit; Grand'Maison, Francois; Hamdy, Sherif; Sola, Patrizia; Ferraro, Diana; Grammond, Pierre; Turkoglu, Recai; Buzzard, Katherine; Skibina, Olga; Yamout, Bassem; Gerlach, Oliver; van Pesch, Vincent; Blanco, Yolanda; Maimone, Davide; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Karabudak, Rana; Iuliano, Gerardo; McGuigan, Chris; Cartechini, Elisabetta; Barnett, Michael; Hughes, Stella; Sa, Maria Jose; Solaro, Claudio; Kappos, Ludwig; Ramo-Tello, Cristina; Cristiano, Edgardo; Hodgkinson, Suzanne; Spitaleri, Daniele; Soysal, Aysun; Petersen, Thor; Slee, Mark; Butler, Ernest; Granella, Franco; de Gans, Koen; McCombe, Pamela; Ampapa, Radek; Van Wijmeersch, Bart; van der Walt, Anneke; Butzkueven, Helmut; Prevost, Julie; Sinnige, L. G. F.; Sanchez-Menoyo, Jose Luis; Vucic, Steve; Laureys, Guy; Van Hijfte, Liesbeth; Khurana, Dheeraj; Macdonell, Richard; Gouider, Riadh; Castillo-Trivino, Tamara; Gray, Orla; Aguera-Morales, Eduardo; Al-Asmi, Abdullah; Shaw, Cameron; Deri, Norma; Al-Harbi, Talal; Fragoso, Yara; Csepany, Tunde; Sempere, Angel Perez; Trevino-Frenk, Irene; Schepel, Jan; Moore, Fraser; Kalincik, Tomas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Abstract

Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ? 1 year, and Expanded Disability Status Scale (EDSS) score ? 3, with ?1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age., This study was financially supported by the National Health and Medical Research Council of Australia (1129189, 1140766, 1080518).

Published
2023

7. 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

14. 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. Gecompliceerde fractuur en antisepsis

Author

Schepel, Jan Arnold Cornelis, Schepel, Jan Arnold Cornelis, Schepel, Jan Arnold Cornelis, and Schepel, Jan Arnold Cornelis

Abstract

Bij het bestudeeren van de geschiedenis der geneeskunde blijkt. dat pas na de vinding van de antiseptische methode door Lister. ± 1865. van cen doeltreffende behandeling van gecompliceerde fracturen sprake heeft kunnen zijn. Was het v66r dien Hjd een zeldzaamheid, dat een ernstig gecompliceerde fractuur zonder amputatie genas, na Lister kan men omgekeerd zeggen. dat de noodzakelijkheid tot amputatie uitzondering werd. Bij de genezing van gecompliceerde £racturen, waarvoor dus vergelijkingsmateriaal met vroeger ontbrak. bleek to en echter de consolidatie veelal lang op zich te laten wachten. ... Zie: Samenvatting

Published
1935

22. Elastofibroma: a Familial Occurrence.

Author

Schepel, Jan A. C., Wille, Jan, Seldenrijk, Cornelis A., and van Ramshorst, Bert

Subjects
*FIBROMAS, *AGE factors in disease
Abstract

Examines the familial occurrence of elastofibroma. Increase in incidence of elastofibroma among women; Correlation between incidence of elastofibroma and age of patient; Clinical manifestations of the disease.

Published
1998
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23. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author

Ibrahima Diouf, Charles B. Malpas, Sifat Sharmin, Izanne Roos, Dana Horakova, Eva Kubala Havrdova, Francesco Patti, Vahid Shaygannejad, Serkan Ozakbas, Guillermo Izquierdo, Sara Eichau, Marco Onofrj, Alessandra Lugaresi, Raed Alroughani, Alexandre Prat, Marc Girard, Pierre Duquette, Murat Terzi, Cavit Boz, Francois Grand'Maison, Sherif Hamdy, Patrizia Sola, Diana Ferraro, Pierre Grammond, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Bassem Yamout, Ayse Altintas, Oliver Gerlach, Vincent van Pesch, Yolanda Blanco, Davide Maimone, Jeannette Lechner‐Scott, Roberto Bergamaschi, Rana Karabudak, Gerardo Iuliano, Chris McGuigan, Elisabetta Cartechini, Michael Barnett, Stella Hughes, Maria José Sa, Claudio Solaro, Ludwig Kappos, Cristina Ramo‐Tello, Edgardo Cristiano, Suzanne Hodgkinson, Daniele Spitaleri, Aysun Soysal, Thor Petersen, Mark Slee, Ernest Butler, Franco Granella, Koen de Gans, Pamela McCombe, Radek Ampapa, Bart Van Wijmeersch, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, L. G. F. Sinnige, Jose Luis Sanchez‐Menoyo, Steve Vucic, Guy Laureys, Liesbeth Van Hijfte, Dheeraj Khurana, Richard Macdonell, Riadh Gouider, Tamara Castillo‐Triviño, Orla Gray, Eduardo Aguera‐Morales, Abdullah Al‐Asmi, Cameron Shaw, Norma Deri, Talal Al‐Harbi, Yara Fragoso, Tunde Csepany, Angel Perez Sempere, Irene Trevino‐Frenk, Jan Schepel, Fraser Moore, Tomas Kalincik, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Laureys, Guy/0000-0002-1708-4373, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Petersen, Thor/0000-0001-5633-2600, Roos, Izanne/0000-0003-0371-3666, Slee, Mark/0000-0003-4323-2453, patti, francesco/0000-0002-6923-0846, Diouf, Ibrahima, Malpas, Charles B., Sharmin , Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Patti, Francesco, Shaygannejad, Vahid, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Hamdy, Sherif, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Turkoglu, Recai, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem, Altintas, Ayse, Gerlach, Oliver, van Pesch, Vincent, Blanco, Yolanda, Maimone, Davide, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Karabudak, Rana, Iuliano, Gerardo, McGuigan, Chris, Cartechini, Elisabetta, Barnett, Michael, Hughes, Stella, Sa, Maria Jose, Solaro, Claudio, Kappos, Ludwig, Ramo-Tello, Cristina, Cristiano, Edgardo, Hodgkinson, Suzanne, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Slee, Mark, Butler, Ernest, Granella, Franco, de Gans, Koen, McCombe, Pamela, Ampapa, Radek, VAN WIJMEERSCH, Bart, van der Walt, Anneke, Butzkueven, Helmut, Prevost, Julie, Sinnige, L. G. F., Sanchez-Menoyo, Jose Luis, Vucic, Steve, Laureys, Guy, Van Hijfte, Liesbeth, Khurana, Dheeraj, Macdonell, Richard, Gouider, Riadh, Castillo-Trivino, Tamara, Gray, Orla, Aguera-Morales, Eduardo, Al-Asmi, Abdullah, Shaw, Cameron, Deri, Norma, Al-Harbi, Talal, Fragoso, Yara, Csepany, Tunde, Sempere, Angel Perez, Trevino-Frenk, Irene, Schepel, Jan, Moore, Fraser, and Kalincik, Tomas

Subjects
marginal structural model, relapse, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Medicine and Health Sciences, Humans, Neurology (clinical), EDSS, immunotherapy, Proportional Hazards Models
Abstract

Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS).Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow -up >= 1 year, and Expanded Disability Status Scale (EDSS) score >= 3, with >= 1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12 -month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45- 0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41- 0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09- 1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age. This study was financially supported by the National Health and Medical Research Council of Australia (1129189, 1140766, 1080518) We thank the patients and their carers who have agreed to participate in the global MSBase cohort study. The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer-Schering, Sanofi-Genzyme, and Teva. The study was conducted separately and apart from the guidance of the sponsors. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.

Published
2023

24. Comparative effectiveness in multiple sclerosis: A methodological comparison.

Author

Roos I, Diouf I, Sharmin S, Horakova D, Havrdova EK, Patti F, Shaygannejad V, Ozakbas S, Izquierdo G, Eichau S, Onofrj M, Lugaresi A, Alroughani R, Prat A, Girard M, Duquette P, Terzi M, Boz C, Grand'Maison F, Sola P, Ferraro D, Grammond P, Turkoglu R, Buzzard K, Skibina O, Yamou B, Altintas A, Gerlach O, van Pesch V, Blanco Y, Maimone D, Lechner-Scott J, Bergamaschi R, Karabudak R, McGuigan C, Cartechini E, Barnett M, Hughes S, Sa MJ, Solaro C, Ramo-Tello C, Hodgkinson S, Spitaleri D, Soysal A, Petersen T, Granella F, de Gans K, McCombe P, Ampapa R, Van Wijmeersch B, van der Walt A, Butzkueven H, Prevost J, Sanchez-Menoyo JL, Laureys G, Gouider R, Castillo-Triviño T, Gray O, Aguera-Morales E, Al-Asmi A, Shaw C, Deri N, Al-Harbi T, Fragoso Y, Csepany T, Sempere AP, Trevino-Frenk I, Schepel J, Moore F, Malpas C, and Kalincik T

Subjects
Humans, Fingolimod Hydrochloride therapeutic use, Natalizumab therapeutic use, Immunosuppressive Agents therapeutic use, Immunologic Factors therapeutic use, Treatment Outcome, Propensity Score, Recurrence, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models., Objective: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models., Methods: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement., Results: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods., Conclusions: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.

Published
2023
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