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51. THE PREVENTION OF POST-PARTUM RELAPSES WITH PROGESTIN AND ESTRADIOL IN MULTIPLE SCLEROSIS (POPART'MUS) TRIAL: RATIONALE, OBJECTIVES AND STATE OF ADVANCEMENT

Author

Vukusic, S, Ionescu, I, El Etr, M, Schumacher, M, Baulieu, Ee, Cornu, C, Confavreux, C, Clanet, M, Brassat, D, Viala, F, Moreau, T, Couvreur, G, Madinier, G, Debouverie, M, Laplaud, D, Wiertlewski, S, Clavelou, P, Aufauvre, D, Pelletier, J, Rico Lamy, A, Edan, G, Le Page, E, Rumbach, L, Berger, E, Hautecoeur, P, Lebrun Frenay, C, Labauge, P, Castelnovo, G, Heinzlef, O, Brochet, B, Ouallet, Jc, Clerc, C, Rieu, L, Lauxerois, M, Hinzelin, G, Froment Sallansonnet, M, Stankoff, B, Borgel, F, Toureille Borlet, L, Minier, D, Coustans, M, Tourniaire, P, Durelli, Luca, Tavella, A, Trojano, M, Carrozzo, A, Patti, F, Zaffaroni, M, and Motti, L.

Published
2009

52. Health-related quality of life in multiple sclerosis: Effects of natalizumab

Author

Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, : S., Grupe, A., Gutmann, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky, : O., Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, : C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Kragt, J. J., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Visual analogue scale, Health Status, Population, Pain, Comorbidity, Placebo, Antibodies, law.invention, Natalizumab, Randomized controlled trial, Quality of life, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, Monoclonal, medicine, Prevalence, Humans, Longitudinal Studies, education, Humanized, education.field_of_study, Expanded Disability Status Scale, Neuroscience (all), business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Female, Patient Satisfaction, Treatment Outcome, United States, Quality of Life, Multiple sclerosis, medicine.disease, Neurology, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Published
2007

53. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity

Author

Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, and Miterski B

Subjects
MSSS, MS, EDSS
Abstract

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Published
2005

57. Is the Choosing Wisely®campaign model applicable to the management of multiple sclerosis in France? A GRESEP pilot study

Author

Trumbic, B., Zéphir, H., Ouallet, J.-C., Le Page, E., Laplaud, D., Bensa, C., and de Sèze, J.

Abstract

Launched in the US in 2012, Choosing Wisely®is a campaign promoted by the American Board of Internal Medicine (ABIM) Foundation with the goal of improving healthcare effectiveness by avoiding wasteful or unnecessary medical tests, treatments and procedures. It uses concise recommendations produced by national medical societies to start discussions between physicians and patients on the relevance of these services as part of a shared decision-making process. The Multiple Sclerosis Focus Group (Groupe de Reflexion Autour de la Sclérose en Plaques; GRESEP) undertook a pilot study to assess the relevance and feasibility of this approach in the management of multiple sclerosis (MS) in France.

Published
2018
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62. Neuromyelitis optica in France: A multicenter study of 125 patients

Author

Collongues, N., primary, Marignier, R., additional, Zephir, H., additional, Papeix, C., additional, Blanc, F., additional, Ritleng, C., additional, Tchikviladze, M., additional, Outteryck, O., additional, Vukusic, S., additional, Fleury, M., additional, Fontaine, B., additional, Brassat, D., additional, Clanet, M., additional, Milh, M., additional, Pelletier, J., additional, Audoin, B., additional, Ruet, A., additional, Lebrun-Frenay, C., additional, Thouvenot, E., additional, Camu, W., additional, Debouverie, M., additional, Creange, A., additional, Moreau, T., additional, Labauge, P., additional, Castelnovo, G., additional, Edan, G., additional, Le Page, E., additional, Defer, G., additional, Barroso, B., additional, Heinzlef, O., additional, Gout, O., additional, Rodriguez, D., additional, Wiertlewski, S., additional, Laplaud, D., additional, Borgel, F., additional, Tourniaire, P., additional, Grimaud, J., additional, Brochet, B., additional, Vermersch, P., additional, Confavreux, C., additional, and de Seze, J., additional

Published
2010
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69. Multiple Sclerosis Severity Score: Using disability and disease duration to rate disease severity

Author

Roxburgh, R. H.S.R., primary, Seaman, S. R., additional, Masterman, T., additional, Hensiek, A. E., additional, Sawcer, S. J., additional, Vukusic, S., additional, Achiti, I., additional, Confavreux, C., additional, Coustans, M., additional, le Page, E., additional, Edan, G., additional, McDonnell, G. V., additional, Hawkins, S., additional, Trojano, M., additional, Liguori, M., additional, Cocco, E., additional, Marrosu, M. G., additional, Tesser, F., additional, Leone, M. A., additional, Weber, A., additional, Zipp, F., additional, Miterski, B., additional, Epplen, J. T., additional, Oturai, A., additional, Sorensen, P. S., additional, Celius, E. G., additional, Lara, N. T., additional, Montalban, X., additional, Villoslada, P., additional, Silva, A. M., additional, Marta, M., additional, Leite, I., additional, Dubois, B., additional, Rubio, J., additional, Butzkueven, H., additional, Kilpatrick, T., additional, Mycko, M. P., additional, Selmaj, K. W., additional, Rio, M. E., additional, Sa, M., additional, Salemi, G., additional, Savettieri, G., additional, Hillert, J., additional, and Compston, D. A.S., additional

Published
2005
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75. ‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study.

Author

Leray, E, Coustans, M, Le Page, E, Yaouanq, J, Oger, J, and Edan, G

Subjects
SCIENTIFIC observation, FOLLOW-up studies (Medicine), MULTIPLE sclerosis, DISEASE relapse, PROGNOSIS, PATIENTS
Abstract

The article presents a study which assess the two definitions of clinically definite benign multiple sclerosis (CDBS). The study made use of the Disability Status Scale (DSS) to assess the disability of 874 patuents with definite relapsing-remitting MS. The result of the study shows that a long-term benign course of multiple sclerosis was failed to be ensured by the 10-year disability scores of DSS 2 or 3.

Published
2013
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76. Impact of pregnancy on conversion to clinically isolated syndrome in a radiologically isolated syndrome cohort.

Author

Lebrun, C, Le Page, E, Kantarci, O, Siva, A, Pelletier, D, and Okuda, DT

Subjects
*PREGNANCY, *CONVERSION disorder, *RADIOLOGY, *NEUROLOGIC examination, *MULTIPLE sclerosis
Abstract

The article presents a study on the effect of pregnancy on the development of clinical event in women diagnosed with radiologically isolated syndrome (RIS). It says that women with RIS undergoes radiological and clinical assessments and outcomes were examined during and after pregnancy. Results showed that a significantly shorter time of conversion to the first neurological event was found in the pregnant group.

Published
2012
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77. Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.

Author

Le Page, E., Leray, E., and Edan, G.

Subjects
*MULTIPLE sclerosis, *CONGESTIVE heart failure, *AMENORRHEA, *DNA topoisomerase II, *PROSTATE cancer treatment, *PATIENTS
Abstract

Background: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS).Methods: Eight hundred and two patients from 12 MS centres (308 relapsing–remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6–12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after.Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS. [ABSTRACT FROM AUTHOR]

Published
2011
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79. Evaluation of the quality of the care pathway for patients with multiple sclerosis in France: Results of an original study of a cohort of 700 patients

Author

Veillard, D., Le Page, E., Epstein, J., Wiertlewski, S., Gallien, P., Hamonic, S., Debouverie, M., and Edan, G.

Abstract

Evaluatingthe quality of the care pathway for patients with chronic diseases, such as multiple sclerosis (MS), is an important issue. Process indicators are a recognized method for evaluating professional practices. However, these tools have been little developed in the field of MS, and few data are available. The aim of this study was to describe, retrospectively, with validated indicators, the quality of the care pathway in a population-based cohort of 700 patients with the first manifestations of the disease occurring between January 1, 2000 and December 31, 2001 and during the first 10 years of disease.

Published
2021
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80. A French observational study about treatment failure under fingolimod in 91 multiple sclerosis patients

Author

Carra-Dalliere, C., Fisselier, M., Cohen, M., Ayrignac, X., Le Page, E., Edan, G., Burghgraeve, V., Papeix, C., Lubetzki, C., Maillart, E., Jerome de Seze, Collongues, N., Gout, O., Deschamps, R., Laplaud, D., Wiertlewski, S., Pelletier, J., Audoin, B., Brassat, D., Clanet, M., Peaureaux, D., Guennoc, A. -M, Ruet, A., Brochet, B., Ouallet, J. -C, Debouverie, M., Pittion, S., Fromont, A., Moreau, T., Taithe, F., Clavelou, P., Zephyr, H., Outteryck, O., Vermersch, P., Charif, M., Thouvenot, E., Mazzola, L., Camdessanche, J. -P, Bourre, B., Lalu, T., Magy, L., Grimaud, J., Lebrun, C., Labauge, P., and Club Francophone Sclerose Plaques

81. The French-Italian Mitoxantrone-Interferon-beta Trial: a 3-year randomised study

Author

Edon, G., Comi, G., Lebrun, C., Brassat, D., Lubetzki, C., Stankoff, B., Tourboh, A., Pelletier, J., Debouverie, M., Contavreux, C., Blanc, S., Roullet, E., Tranchant, C., Hautecoeur, R., Mackowiak, A., Magy, L., Rumbach, L., Gout, O., Aufauvre, D., Clavelou, R., Moreau, T., Mancardi, G. L., Zaffaroni, M., Amato, M. P., Trojano, M., Durelli, L., Veillard, D., Le Page, E., Massimo Filippi, and Morrissey, S.

83. Radiologically isolated syndrome: a 10-year follow-up study to identify factors predicting a clinical event

Author

Lebrun-Frenay, C., Kantarci, O., Siva, A., Cara-Dalliere, C., Louapre, C., Durand-Dubief, F., Thouvenot, E., Vemersch, P., Matilde Inglese, Stefano, N., Mathey, G., Le Page, E., Uygunoglu, U., Tintore, M., Laplaud, D., Seze, J., Ciron, J., Pelletier, J., Brochet, B., Berger, E., Bensa, C., Bourre, B., Casez, O., Mondot, L., Zeydan, B., Cohen, M., Azevedo, C., Makhani, N., Sormani, M. P., Pelletier, D., and Okuda, D.

84. Switching from natalizumab to fingolimod: risk of disease reactivation during the washout period is due to the previous activity of the disease. Follow-up of the ENIGM survey

Author

Cohen, M., Maillart, E., Papeix, C., Vukusic, S., Brassat, D., Seze, J., Tourbah, A., Wiertlewski, S., Laplaud, D., Camu, W., Courtois, S., Derouiche, F., Chambaud, L., Boulay, C., Brochet, B., Debouverie, M., Casez, O., Heinzlef, O., Ouallet, J., Stankoff, B., Castelnovo, G., Le Page, E., Defer, G., Derache, N., Anne, O., Berger, E., Camdessanche, J., Kopf, A., Fleury, M., Malikova, I., Pelletier, J., Al Khedr, A., Zaenker, C., Edan, G., Moreau, T., Fromont, A., Rico, A., Blanc, F., nicolas collongues, Barth, P., Louiset, P., Pittion, S., Clavelou, P., Thaite, F., Vermersch, P., Sephir, H., Creange, A., Gout, O., Guennoc, A., Coustans, M., Thaurin, G., Lallement, F., Rouhart, F., Thouvenot, E., Labauge, P., Seeldrayers, P., Lebrun, C., and Club Francophone Sclerose Plaques

87. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Author

Patrick Vermersch, Ivania Patry, Nicolas Maubeuge, Catherine Lubetzki, Ofsep Study Groups, David-Axel Laplaud, Bruno Stankoff, Bruno Brochet, Eric Thouvenot, Céline Labeyrie, Jean-Philippe Camdessanché, Olivier Gout, Laure Michel, Chantal Nifle, Abdullatif Al Khedr, Emmanuelle Leray, Gilles Edan, Marc Debouverie, Laetitia Barbin, David Brassat, Yohann Foucher, Thibault Moreau, Romain Casey, Jean Pelletier, Christine Lebrun-Frenay, Sandra Vukusic, Laurent Magy, Olivier Heinzlef, Philippe Cabre, Caroline Papeix, Ayman Tourbah, Gilles Defer, Abir Wahab, Pierre Clavelou, Eric Berger, Jérôme De Seze, A.-M. Guennoc, Fabien Rollot, Olivier Casez, Sandrine Wiertlewski, Thomas Debroucker, Pierre Labauge, Bertrand Bourre, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Neurologie [Lyon], CHU Lyon, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Rennes], Université de Rennes (UR), Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Public Health Agency of Canada, CHI Poissy-Saint-Germain, Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherches Critiques sur le Droit (CERCRID), Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Neurologie [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), École des Hautes Études en Santé Publique [EHESP] (EHESP), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Supported by Fondation ARSEP, CHU Nantes (Appel d’Offre Interne), and Association ANTARES. The French Observatoire of Multiple Sclerosis is supported by a grant provided by the French State and handled by the Agence Nationale de la Recherche, within the framework of the Investments for the Future program, under the reference ANR-10-COHO-002. The study was supported by West Neurosciences Network and Société Francophone de Scl´erose en Plaques, Fondation ARSEP, and by Appel d’Offre Interne du CHU de Nantes., SFSEP and OFSEP groups : Fontaine B, Marignier R, Durand-Dubief F, Mathey G, Le Page E, Peaureaux-Averseng D, Ouallet JC, Ruet A, Collongues N, Hautecoeur P, Zephir H, Maillard E, Cohen M, Derache N, Branger P, Ayrignac X, Carra-Dalliere C, Fromont A, Chamard-Witkowski L, Taithe F, Moisset X, Audoin B, Rico-Lamy A, Castelnovo G, Giannesini C, Fagniez O, Bensa C, Gueguen A, Kasonde IT, De Vilmarest A, Montcuquet A, Vaillants M, Beltran S, Creange A, Ayache S, Abdellaoui M, Pottier C, Slesari I, Deburghraeve V, Neau JP, Servan J, Pico F, Henry C, Hankiewicz K., Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de neurologie, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Saint-Etienne, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2), Fondation Ophtalmologique Rothschild, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Montpellier (UM)-Université Montpellier 1 (UM1), Le Bihan, Sylvie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Adult, Male, medicine.medical_specialty, Toluidines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hydroxybutyrates, Effectiveness, Dimethyl fumarate, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Adverse effect, ComputingMilieux_MISCELLANEOUS, Intention-to-treat analysis, Expanded Disability Status Scale, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Fingolimod Hydrochloride, Odds ratio, Middle Aged, Discontinuation, Treatment Outcome, chemistry, Crotonates, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectiveIn this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.MethodsA total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated.ResultsThe confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001).ConclusionsAfter 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.

Published
2019
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88. Multiple sclerosis severity score: Using disability and disease duration to rate disease severity

Author

Maria José Sá, Justin P. Rubio, Bianca Miterski, S. R. Seaman, Jörg T. Epplen, Iuliana Achiti, Monica Marta, M. Coustans, Sandra Vukusic, G V McDonnell, Annette Bang Oturai, Richard Roxburgh, Maria Edite Rio, Pablo Villoslada, Bénédicte Dubois, Fabiana Tesser, Maurizio Leone, Christian Confavreux, T Masterman, Marcin P. Mycko, Gilles Edan, N. Téllez Lara, Ana Martins da Silva, Alexandra Weber, Stephen Sawcer, E. Le Page, Giuseppe Salemi, Giovanni Savettieri, P. Soelberg Sørensen, Anke Hensiek, Xavier Montalban, D. A. S. Compston, Maria Giovanna Marrosu, Helmut Butzkueven, Krzysztof Selmaj, Frauke Zipp, Maria Liguori, Isabel Leite, Stanley Hawkins, Elisabeth Gulowsen Celius, Jan Hillert, Maria Trojano, Trevor J. Kilpatrick, Eleonora Cocco, Chemical Biology 2, ROXBURGH RHSR, SEAMAN SR, MASTERMAN T, HENSIEK AE, SAWCER SJ, VUKUSIC S, ACHITI I, CONFAVREUX C, COUSTANS M, LE PAGE E, EDAN G, MCDONNELL GV, HAWKINS S, TROJANO M, LIGUORI M, COCCO E, MARROSU MG, TESSERE F, LEONE MA, WEBER A, ZIPP F, MITERSKI B, EPPLEN JT, OTURAI A, SOELBERG-SORENSEN P, CELIUS EG, TELLEZ LARA N, MONTALBAN X, VILLOSLADA P, SILVA AM, MARTA M, LEITE I, DUBOIS B, RUBIO J, BUTZKUEVEN H, KILPATRICK T, MYCKO MP, SELMAJ KW, RIO ME, SA M, SALEMI G, SAVETTIERI G, HILLERT J, and COMPSTON DAS

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Cross-sectional study, Models, Neurological, Disease, SUSCEPTIBILITY, Severity of Illness Index, Cohort Studies, Disability Evaluation, Predictive Value of Tests, Recurrence, Severity of illness, medicine, Humans, Longitudinal Studies, Age of Onset, Models, Statistical, Expanded Disability Status Scale, business.industry, Multiple sclerosis, OUTCOME MEASURE, Reproducibility of Results, NATURAL-HISTORY, Middle Aged, Prognosis, medicine.disease, Cross-Sectional Studies, Predictive value of tests, Disease Progression, Physical therapy, Female, France, Neurology (clinical), Age of onset, business, Cohort study
Abstract

Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Published
2005

89. Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis: A Multicenter Real-Life Study.

Author

Hay M, Rollot F, Casey R, Kerbrat A, Edan G, Mathey G, Labauge P, De Sèze J, Vukusic S, Laplaud DA, Papeix C, Moreau T, Thouvenot E, Defer G, Lebrun-Frénay C, Ciron J, Berger E, Stankoff B, Clavelou P, Maillart E, Heinzlef O, Zéphir H, Ruet A, Casez O, Moulin S, Al-Khedr A, Bourre B, Pelletier J, Magy L, Neau JP, Camdessanché JP, Doghri I, Wahab A, Tchikviladzé M, Labeyrie C, Hankiewicz K, Le Page E, and Michel L

Subjects
Humans, Female, Male, Middle Aged, Retrospective Studies, Disease Progression, Antibodies, Monoclonal, Humanized therapeutic use, Registries, Magnetic Resonance Imaging, France epidemiology, Treatment Outcome, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive diagnostic imaging, Rituximab therapeutic use, Immunologic Factors therapeutic use, Antigens, CD20 immunology
Abstract

Background and Objectives: Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort., Methods: This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity., Results: A total of 1,184 patients (426 treated and 758 untreated) fulfilled the inclusion criteria. Median age (Q1-Q3) was 56 years (49.3-63.8), and 52.7% were female. Among treated patients, 295 received rituximab, whereas 131 received ocrelizumab. At baseline, anti-CD20-treated patients were younger (median 51.9 vs 58.6 years, Cohen d = 0.683) and had more active disease (54.5 vs 27.8%, Cohen d = 0.562). 91.6% were drug-naive at inclusion. In time to first CDP analysis, no statistical significance was observed (hazard ratio [HR], 1.13; 95% CI 0.93-1.36, p = 0.2113). In time to first relapse analysis, a nonsignificant trend toward fewer patients relapsing in the treated group was observed (HR 0.83; 95% CI 0.48-1.28, p = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group., Discussion: Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS., Classification of Evidence: This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.

Published
2024
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90. Choroid plexus enlargement correlates with periventricular pathology but not with disease activity in radiologically isolated syndrome.

Author

Landes-Château C, Ricigliano VA, Mondot L, Thouvenot E, Labauge P, Louapre C, Zéphir H, Durand-Dubief F, Le Page E, Siva A, Cohen M, Yazdan Panah A, Azevedo CJ, Okuda DT, Stankoff B, and Lebrun-Frénay C

Subjects
Humans, Female, Male, Adult, Middle Aged, Retrospective Studies, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis pathology, Choroid Plexus pathology, Choroid Plexus diagnostic imaging, Magnetic Resonance Imaging, Demyelinating Diseases diagnostic imaging, Demyelinating Diseases pathology
Abstract

Background: Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS)., Objectives: This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers., Methods: RIS individuals were included retrospectively and compared with HC. ChPs were automatically segmented using an in-house automated algorithm and manually corrected., Results: A total of 124 patients fulfilled the 2023 RIS criteria, and 55 HCs were included. We confirmed that ChPs are enlarged in RIS versus HC (mean (±SD) normalized ChP volume: 17.24 (±4.95) and 11.61 (±3.58), respectively, p < 0.001). Larger ChPs were associated with more periventricular lesions (ρ = 0.26; r 2 = 0.27; p = 0.005 for the correlation with lesion volume, and ρ = 0.2; r 2 = 0.21; p = 0.002 for the correlation with lesion number) and lower thalamic volume (ρ = -0.38; r 2 = 0.44; p < 0.001), but not with lesions in other brain regions. Conversely, ChP volume did not correlate with biological markers. No significant difference in ChP volume was observed between subjects who presented or did not have a clinical event or between those with or without imaging disease activity., Conclusions: This study provides evidence that ChP volume is higher in RIS and is associated with measures reflecting periventricular pathology but does not correlate with biological, radiological, or clinical markers of disease activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.L.-C. received a Neuromod Institute grant for her PhD.VAGR reports fees for traveling from Novartis, Merck, Biogen, and Roche, speaker’s honoraria from Novartis, Sandoz, Merck, Biogen, Roche, consulting fees from Biogen, Merck, Novartis, Janssen, M3 Global Research, and Atheneum Partners, all outside of the submitted work.L. M. has no conflict of interest.E. T. received consulting and lecturing fees, travel grants, or unconditional research support from the following pharmaceutical companies: Actelion, Biogen, BMS, Janssen, Merck, Novartis, Roche, and Teva Pharma.P. L. has no financial conflicts related to this work.C. L. has received speaker or consulting fees from Biogen, Merck, Novartis, Sanofi, and Roche and a research grant (to the institution) from Biogen.H. Z. has no disclosure related to this work. HZ received consulting fees from ALEXION, HORIZON THERAPEUTICS, ROCHE, BIOGEN IDEC, SANOFI, JANSSEN, and research support from ROCHE and NOVARTIS.F. D.D. has no financial conflicts related to this work.E. L.P. has no financial conflicts related to this work.A. S. has no financial conflicts related to this work and has received research grants from The Turkish Multiple Sclerosis Society, The Scientific and Technological Research Council Of Turkiye, and Istanbul University-Cerrahpasa Research Support Funds. He has received consultancy fees from Roche Ltd, Merck-Serono, Biogen Idec/Gen Pharma of Turkiye, Sanofi-Genzyme, Novartis, and Alexion and received honoraria for lectures from Sanofi-Genzyme, Novartis, Roche Ltd., and Teva—registration coverage for attending scientific congresses or symposia from Sanofi-Genzyme and Alexion.M. C. has no conflict of interest.A. YP. has no financial conflicts related to this work.C. J.A. has no conflict of interest with this work.D. T.O. received personal compensation for consulting and advisory services from Biogen, Eisai, EMD Serono, Genentech, Genzyme/Sanofi, Moderna, RVL Pharmaceuticals, Inc., Zenas BioPharma, and research support from EMD Serono/Merck and Novartis. D.T.O. has issued national and international patents and pending patents related to other developed technologies. D.T.O. received royalties for intellectual property licensed by The Board of Regents of The University of Texas System and is also the Founder of Revert Health Inc.B. S. has received personal speaker fees from Janssen, Biogen, Novartis, Merck, and Sanofi, as well as research support (to the institution) from Merck, Roche, and Novartis.C. L-F. has no conflict of interest.

Published
2024
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91. Microstructural Damage and Repair in the Spinal Cord of Patients With Early Multiple Sclerosis and Association With Disability at 5 Years.

Author

Gaubert M, Combès B, Bannier E, Masson A, Caron V, Baudron G, Ferré JC, Michel L, Le Page E, Stankoff B, Edan G, Bodini B, and Kerbrat A

Subjects
Humans, Female, Male, Adult, Longitudinal Studies, Middle Aged, Atrophy pathology, Disease Progression, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting pathology, Magnetic Resonance Imaging, Spinal Cord pathology, Spinal Cord diagnostic imaging
Abstract

Background and Objectives: The dynamics of microstructural spinal cord (SC) damage and repair in people with multiple sclerosis (pwMS) and their clinical relevance have yet to be explored. We set out to describe patient-specific profiles of microstructural SC damage and change during the first year after MS diagnosis and to investigate their associations with disability and SC atrophy at 5 years., Methods: We performed a longitudinal monocentric cohort study among patients with relapsing-remitting MS: first relapse <1 year, no relapse <1 month, and high initial severity on MRI (>9 T2 lesions on brain MRI and/or initial myelitis). pwMS and age-matched healthy controls (HCs) underwent cervical SC magnetization transfer (MT) imaging at baseline and at 1 year for pwMS. Based on HC data, SC MT ratio z -score maps were computed for each person with MS. An index of microstructural damage was calculated as the proportion of voxels classified as normal at baseline and identified as damaged after 1 year. Similarly, an index of repair was also calculated (voxels classified as damaged at baseline and as normal after 1 year). Linear models including these indices and disability or SC cross-sectional area (CSA) change between baseline and 5 years were implemented., Results: Thirty-seven patients and 19 HCs were included. We observed considerable variability in the extent of microstructural SC damage at baseline (0%-58% of SC voxels). We also observed considerable variability in damage and repair indices over 1 year (0%-31% and 0%-20%), with 18 patients showing predominance of damage and 18 predominance of repair. The index of microstructural damage was associated positively with the Expanded Disability Status Scale score ( r = 0.504, p = 0.002) and negatively with CSA change ( r = -0.416, p = 0.02) at 5 years, independent of baseline SC lesion volume., Discussion: People with early relapsing-remitting MS exhibited heterogeneous profiles of microstructural SC damage and repair. Progression of microstructural damage was associated with disability progression and SC atrophy 5 years later. These results indicate a potential for microstructural repair in the SC to prevent disability progression in pwMS.

Published
2025
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92. Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis.

Author

Gavoille A, Rollot F, Casey R, Kerbrat A, Le Page E, Bigaut K, Mathey G, Michel L, Ciron J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al-Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanché JP, Doghri I, Moulin S, Ben-Nasr H, Labeyrie C, Hankiewicz K, Neau JP, Pottier C, Nifle C, Manchon E, Lapergue B, Wiertlewski S, De Sèze J, Vukusic S, and Laplaud DA

Subjects
Humans, Female, Male, Adult, Middle Aged, Cohort Studies, Spinal Cord diagnostic imaging, Spinal Cord pathology, Brain diagnostic imaging, Disease Progression, Gadolinium, Registries, Magnetic Resonance Imaging methods, Recurrence, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development., Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI)., Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection., Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise., Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated., Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs., Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Published
2024
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93. Visual recovery after oral high-dose methylprednisolone in acute inflammatory optic neuropathy.

Author

Boureaux E, Laurent C, Rodriguez T, Le Page E, and Mouriaux F

Abstract

Purpose: High doses of venous corticosteroids are currently the only validated treatment for the management of optic neuritis (ON). The objective is to assess the changes in visual function parameters after oral high-dose methylprednisolone in patients with ON., Methods: A retrospective analysis of patients with acute ON was performed. Patients received 1 g per day of oral methylprednisolone for 3 to 5 days. Visual function was measured using the ETDRS test for visual acuity, 30-2 automated visual field test, contrast sensitivity test, and color vision test before treatment, 4 days, 2 weeks, 1 month and 3 months, and 6 months following treatment. To assess anatomical changes, optical coherence tomography of the ganglion cells was performed at various timepoints., Results: Between September 2014 and September 2016, a total of 29 patients were included in the study. More than 80% of patients had recovered normal visual acuity after 3 and 6 months. This recovery of all parameters of visual function was observed as early as 4 days but occurred predominantly within 15 days after the initiation of treatment. We observed a thinning of the ganglion cell layer during the follow-up, which mainly occurs within one month. The P100 wave of visually evoked potentials was discernible in all patients at 6 months. During the 6 years of follow-up, 2 patients had experienced a relapse of ON. No serious adverse effects were observed., Conclusion: This study demonstrated a rapid recovery of all visual function parameters after oral high-dose methylprednisolone ON with no serious adverse effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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94. High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS.

Author

Jouvenot G, Courbon G, Lefort M, Rollot F, Casey R, Le Page E, Michel L, Edan G, de Seze J, Kremer L, Bigaut K, Vukusic S, Mathey G, Ciron J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Laplaud DA, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al-Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanché JP, Doghri I, Moulin S, Ben-Nasr H, Labeyrie C, Hankiewicz K, Neau JP, Pottier C, Nifle C, Collongues N, and Kerbrat A

Subjects
Humans, Female, Male, Middle Aged, Cohort Studies, Fingolimod Hydrochloride therapeutic use, Immunologic Factors therapeutic use, Immunologic Factors administration & dosage, Registries, Aged, Withholding Treatment, Immunosuppressive Agents therapeutic use, Multiple Sclerosis drug therapy, Natalizumab therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Importance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity., Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET., Design, Setting, and Participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022., Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab., Main Outcomes and Measures: Time to first relapse., Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy., Conclusion and Relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Published
2024
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95. Comparison of 2 Methods for Estimating Multiple Sclerosis-Related Mortality.

Author

Rollot F, Uhry Z, Dantony E, Vukusic S, Debouverie M, Le Page E, Ciron J, Ruet A, De Sèze J, Zéphir H, Labauge P, Defer G, Lebrun-Frenay C, Moreau T, Laplaud DA, Berger E, Clavelou P, Pelletier J, Thouvenot E, Heinzlef O, Camdessanche JP, Fauvernier M, Remontet L, and Leray E

Subjects
Humans, Female, Probability, Multiple Sclerosis epidemiology
Abstract

Background and Objectives: Determining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast 2 frameworks to estimate probabilities of death attributed to MS (P MS ) and other causes (P other ): the cause-specific framework (CSF), which requires the causes of death, and the excess mortality framework (EMF), which does not., Methods: We used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n = 37,524) and from a comparative subset where causes of death were available (4,004 women with relapsing-onset MS [R-MS]). In CSF, the probabilities were estimated using the Aalen-Johansen method. In EMF, they were estimated from the excess mortality hazard, which is the additional mortality among patients with MS as compared with the expected mortality in the matched general population. P MS values were estimated at 30 years of follow-up, (1) with both frameworks in the comparative subset, by age group at onset, and (2) with EMF only in the OFSEP population, by initial phenotype, sex, and age at onset., Results: In the comparative subset, the estimated 30-year P MS values were greater using EMF than CSF: 10.9% (95% CI 8.3-13.6) vs 8.7% (6.4-11.8) among the youngest and 20.4% (11.3-29.5) vs 16.2% (8.7-30.2) for the oldest groups, respectively. In the CSF, probabilities of death from unknown causes ranged from 1.5% (0.7-3.0) to 6.4% (2.5-16.4), and even after their reallocation, P MS values remained lower with CSF than with EMF. The estimated probabilities of being alive were close using the 2 frameworks, and the estimated P Other (EMF vs CSF) was 2.6% (2.5-2.6) vs 2.1% (1.2-3.9) and 18.1% (16.9-19.3) vs 26.4% (16.5-42.2), respectively, for the youngest and oldest groups. In the OFSEP population, the estimated 30-year P MS values ranged from 7.5% (6.4-8.7) to 24.0% (19.1-28.9) in patients with R-MS and from 25.4% (21.1-29.7) to 36.8% (28.3-45.3) in primary progressive patients, depending on sex and age., Discussion: EMF has the great advantage of not requiring death certificates, their quality being less than optimal. Conceptually, it also seems more relevant because it avoids having to state, for each individual, whether death was directly or indirectly caused by MS or whether it would have occurred anyway, which is especially difficult in such chronic diseases.

Published
2023
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96. Escalation Versus Induction/High-Efficacy Treatment Strategies for Relapsing Multiple Sclerosis: Which is Best for Patients?

Author

Edan G and Le Page E

Subjects
Humans, Immunosuppressive Agents, Natalizumab adverse effects, Cladribine therapeutic use, Alemtuzumab therapeutic use, Mitoxantrone therapeutic use, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

After more than 2 decades of recommending an escalating strategy for the treatment of most patients with multiple sclerosis, there has recently been considerable interest in the use of high-efficacy therapies in the early stage of the disease. Early intervention with induction/high-efficacy disease-modifying therapy may have the best risk-benefit profile for patients with relapsing-remitting multiple sclerosis who are young and have active disease, numerous focal T2 lesions on spinal and brain magnetic resonance imaging, and no irreversible disability. Although we have no curative treatment, at least seven classes of high-efficacy drugs are available, with two main strategies. The first strategy involves the use of high-efficacy drugs (e.g., natalizumab, sphingosine 1-phosphate receptor modulators, or anti-CD20 drugs) to achieve sustained immunosuppression. These can be used as a first-line therapy in many countries. The second strategy entails the use of one of the induction drugs (short-term use of mitoxantrone, alemtuzumab, cladribine, or autologous hematopoietic stem cell transplant) that are mainly recommended as a second-line or third-line treatment in patients with very active or aggressive multiple sclerosis disease. Early sustained immunosuppression exposes patients to heightened risks of infection and cancer proportionate to cumulative exposure, and induction drugs expose patients to similar risks during the initial post-treatment period, although these risks decrease over time. Their initial potential safety risks should now be revisited, taking account of long-term data and some major changes in their regimens: natalizumab with the long-term monitoring of John Cunningham virus; use of monthly courses of mitoxantrone with maximum cumulative doses of 36-72 mg/m 2 , followed by a safer disease-modifying drug; cladribine with only 2-weekly treatment courses required in years 1 and 2 and no systematic treatment for the following 2 years; alemtuzumab, whose safety and clinical impacts have now been documented for more than 6 years after the last infusion; and autologous haematopoietic stem cell transplant, which dramatically reduces transplantation-related mortality with a new regimen and guidelines. Escalation and induction/high-efficacy treatments need rigorous magnetic resonance imaging monitoring. Monitoring over the first few years, using the MAGNIMS score or American Academy of Neurology guidelines, considerably improves prediction accuracy and facilitates the selection of patients with relapsing-remitting multiple sclerosis requiring aggressive treatment., (© 2023. The Author(s).)

Published
2023
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97. Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial.

Author

Lebrun-Frénay C, Siva A, Sormani MP, Landes-Chateau C, Mondot L, Bovis F, Vermersch P, Papeix C, Thouvenot E, Labauge P, Durand-Dubief F, Efendi H, Le Page E, Terzi M, Derache N, Bourre B, Hoepner R, Karabudak R, De Seze J, Ciron J, Clavelou P, Wiertlewski S, Turan OF, Yucear N, Cohen M, Azevedo C, Kantarci OH, Okuda DT, and Pelletier D

Subjects
Humans, Female, Adult, Crotonates therapeutic use, Toluidines therapeutic use, Hydroxybutyrates, Double-Blind Method, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy, Demyelinating Diseases drug therapy
Abstract

Importance: Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system., Objective: To determine the time to onset of symptoms consistent with MS., Design, Setting, and Participants: From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144., Interventions: Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred., Main Outcomes: Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs., Results: Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant., Conclusion and Relevance: Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum., Trial Registration: ClinicalTrials.gov Identifier: NCT03122652.

Published
2023
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98. The radiologically isolated syndrome: revised diagnostic criteria.

Author

Lebrun-Frénay C, Okuda DT, Siva A, Landes-Chateau C, Azevedo CJ, Mondot L, Carra-Dallière C, Zephir H, Louapre C, Durand-Dubief F, Le Page E, Bensa C, Ruet A, Ciron J, Laplaud DA, Casez O, Mathey G, de Seze J, Zeydan B, Makhani N, Tutuncu M, Levraut M, Cohen M, Thouvenot E, Pelletier D, and Kantarci OH

Subjects
Humans, Female, Adult, Middle Aged, Male, Disease Progression, Magnetic Resonance Imaging, Risk Factors, Demyelinating Diseases pathology, Multiple Sclerosis diagnostic imaging
Abstract

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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99. Switching from natalizumab administration at the day hospital to administration at home. A 1 year prospective study of patient experience and quality of life in 30 consecutive patients with multiple sclerosis (TYSAD-35).

Author

Lamy S, Veillard D, Doyen H, Kerbrat A, Michel L, Chretien E, Ousmen A, Edan G, and Le Page E

Subjects
Humans, Natalizumab adverse effects, Prospective Studies, Immunologic Factors adverse effects, Quality of Life, Pandemics, Patient Outcome Assessment, Hospitals, Multiple Sclerosis drug therapy, Multiple Sclerosis epidemiology, COVID-19, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Background: In the context of the COVID-19 pandemic, French health authorities allowed the home administration of natalizumab by a healthcare-at-home service. We evaluated the patients' perception of care quality following the transition from day-hospital to home natalizumab administration., Methods: Thirty relapsing-remitting multiple sclerosis (MS) patients treated with natalizumab were prospectively evaluated for one year after changing onto a home treatment procedure, using MusiCare, the first MS-specific questionnaire to evaluate patient experience and MusiQol. A numerical rating scale score for satisfaction and a dedicated questionnaire concerning patient experience were completed after each infusion. The primary endpoint was the mean difference in MusiCare score between baseline and 12 months., Results: From June 2020 to November 2021, 306 infusions were performed at home. Three patients withdrew from the study (one lost to follow-up and two preferred to return at the day hospital). No worsening of patient experience or quality of life was observed. The mean scores of the Musicare dimensions were higher at 12 months than at baseline, significantly for the "relationship with healthcare professionals" (p = 0.0203). The MusiQol global score remained stable but the coping and friendship dimensions were significantly better at M12 than at baseline (p = 0.0491 and p = 0.0478, respectively). The satisfaction questionnaire highlighted some pain during the infusions (21.8%) and contradictions between healthcare professionals (17.2%). The mean score for satisfaction with care was 9.1/10. No safety concerns were identified., Conclusion: The positive experience of patients with home natalizumab administration provides an important opportunity to improve the quality of patient care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. E. Le Page received honoraria for consulting or lectures, invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis, Alexion, Roche; research support from Teva and Biogen; academic research grants from PHRC and LFSEP, and travel grant from ARSEP Foundation. H. Doyen received honoraria for consulting from Biogen. L. Michel received honoraria for consulting from sanofi, roche, Janssen, celgene, Merck and novartis. S. Lamy, D.Veillard, A. Kerbrat, E. Chretien, A. Ousmen and G. Edan reports no disclosures., (Copyright © 2023. Published by Elsevier B.V.)

Published
2023
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100. Investigating the Long-term Effect of Pregnancy on the Course of Multiple Sclerosis Using Causal Inference.

Author

Gavoille A, Rollot F, Casey R, Debouverie M, Le Page E, Ciron J, De Seze J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Laplaud DA, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanche JP, Maurousset A, Moulin S, Ben NH, Boulos DD, Hankiewicz K, Neau JP, Pottier C, Nifle C, Rabilloud M, Subtil F, and Vukusic S

Subjects
Pregnancy, Humans, Female, Cohort Studies, Probability, Recurrence, Disease Progression, Multiple Sclerosis epidemiology, Disabled Persons, Multiple Sclerosis, Relapsing-Remitting
Abstract

Background and Objectives: The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery)., Methods: We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up)., Results: We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate., Discussion: Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias., (© 2022 American Academy of Neurology.)

Published
2023
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