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1. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

Lefort, M., Sharmin, S., Andersen, J. B., Vukusic, S., Casey, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., De Sèze, J., Maillart, E., Zephir, H., Labauge, P., Defer, G., Lebrun-Frenay, C., Moreau, T., Berger, E., Clavelou, P., Pelletier, J., Stankoff, B., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Wahab, A., Camdessanché, J. P., Maurousset, A., Ben Nasr, H., Hankiewicz, K., Pottier, C., Maubeuge, N., Dimitri-Boulos, D., Nifle, C., Laplaud, D. A., Horakova, D., Havrdova, E. K., Alroughani, R., Izquierdo, G., Eichau, S., Ozakbas, S., Patti, F., Onofrj, M., Lugaresi, A., Terzi, M., Grammond, P., Grand’Maison, F., Yamout, B., Prat, A., Girard, M., Duquette, P., Boz, C., Trojano, M., McCombe, P., Slee, M., Lechner-Scott, J., Turkoglu, R., Sola, P., Ferraro, D., Granella, F., Shaygannejad, V., Prevost, J., Maimone, D., Skibina, O., Buzzard, K., Van der Walt, A., Karabudak, R., Van Wijmeersch, B., Csepany, T., Spitaleri, D., Vucic, S., Koch-Henriksen, N., Sellebjerg, F., Soerensen, P. S., Hilt Christensen, C. C., Rasmussen, P. V., Jensen, M. B., Frederiksen, J. L., Bramow, S., Mathiesen, H. K., Schreiber, K. I., Butzkueven, H., Magyari, M., Kalincik, T., and Leray, E.

Published
2022
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3. Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI

Author

Brochet, B., Casey, R., Cotton, F., De Sèze, J., Douek, P., Guillemin, F., Laplaud, D., Lebrun-Frenay, C., Mansuy, L., Moreau, T., Olaiz, J., Pelletier, J., Rigaud-Bully, C., Stankoff, B., Vukusic, S., Marignier, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., Collongues, N., Lubetzki, C., Vermersch, P., Labauge, P., Defer, G., Cohen, M., Fromont, A., Wiertlewsky, S., Berger, E., Clavelou, P., Audoin, B., Giannesini, C., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Créange, A., Camdessanché, J.-P., Faure, J., Maurousset, A., Patry, I., Hankiewicz, K., Pottier, C., Maubeuge, N., Labeyrie, C., Nifle, C., Ameli, R., Anxionnat, R., Attye, A., Bannier, E., Barillot, C., Ben Salem, D., Boncoeur-Martel, M.-P., Bonneville, F., Boutet, C., Brisset, J.-C., Cervenanski, F., Claise, B., Commowick, O., Constans, J.-M., Dardel, P., Desal, H., Dousset, Vincent, Durand-Dubief, F., Ferre, J.-C., Gerardin, E., Glattard, T., Grand, S., Grenier, T., Guillevin, R., Guttmann, C., Krainik, A., Kremer, S., Lion, S., Menjot de Champfleur, N., Mondot, L., Outteryck, O., Pyatigorskaya, N., Pruvo, J.-P., Rabaste, S., Ranjeva, J.-P., Roch, J.-A., Sadik, J.C., Sappey-Marinier, D., Savatovsky, J., Tanguy, J.-Y., Tourbah, A., Tourdias, T., Roca, P., Colas, L., Tucholka, A., Rubini, P., Cackowski, S., Ding, J., Budzik, J.-F., Renard, F., Doyle, S., Barbier, E.L., Bousaid, I., Lassau, N., and Verclytte, S.

Published
2020
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4. Urinary tract infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Donzé, C., Papeix, C., Lebrun-Frénay, C., Collongues, N., de Seze, M., Dinh, A., Even, A., Scheiber-Nogueira, C., Bensa, C., Bourre, B., Carra-Dallière, C., Ciron, J., Cohen, M., Guennoc, A.M., Louapre, C., Lebreton, F., Michel, L., Maillart, E., Audoin, B., Ayrignac, X., Bernady, P., Brochet, B., Clavelou, P., Colamarino, R., Declemy, A., de Seze, J., Derache, N., Faucheux, J.-M., Heinzlef, O., Labauge, P., Laplaud, D., Lepage, E., Leray, E., Magy, L., Mathey, G., Mekies, C., Mondain, V., Planque, E., Pelletier, J., Pittion, S., Stankhof, B., Tournaire, P., Thouvenot, E., Vukusic, S., Wiertlevski, S., Zephir, H., Alchaar, H., Androdias, G., Benazet, M., Bensmail, D., Biotti, D., Blanchard-Dauphin, A., Bonnan, M., Boutière, C., Branger, P., Bresch, S., Bru, J.-P., Camdessanché, J.-P., Castel Canal, E., Coustans, M., Casez, O., Castan, B., Creange, A., Creisson, E., De Broucker, T., Depaz, R., Douay, X., Dulau, C., Durand-Dubief, F., Fagniez, O., Faucher, M., Floch, A., Fournier, M., Fromont, A., Gallien, P., Gamé, X., Gault, D., Gayou, A., Giroux, M., Gout, O., Grimaud, J., Hautecoeur, P., Kerbrat, A., Kremer, L., Kwiatkowski, A., Labeyrie, C., Lachaud, S., Lanctin-Garcia, C., Lanotte, L., Manchon, E., Maurousset, A., Milor, A.-M., Moisset, X., Mont-Cuquet, A., Moreau, T., Ouallet, J.-C., Patry, I., Peaureaux, D., Pouget, M.-C., Pourcher Martinez, V., Radot, C., Ruet, A., Saint-Val, C., Salmon, A., Taithe, F., Tatevin, P., Vaillant, M., Stahl, J.-P., Vuoto, F., Zaenker, C., and Lebrun-Frenay, C.

Published
2020
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5. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Abadie, V., Achour, C., Ader, F., Alchaar, H., Alkhedr, A., Andreux, F., Androdias, G., Arjmand, R., Audoin, B., Audry, D., Aufauvre, D., Autreaux, C., Ayrignac, X., Bailbe, M., Benazet, M., Bensa, C., Bensmail, D., Berger, E., Bernady, P., Bertagna, Y., Biotti, D., Blanchard-Dauphin, A., Bonenfant, J., Bonnan, M., Bonnemain, B., Borgel, F., Botelho-Nevers, E., Boucly, S., Bourre, B., Boutière, C., Branger, P., Brassat, D., Bresch, S., Breuil, V., Brochet, B., Brugeilles, H., Bugnon, P., Cabre, P., Camdessanché, J.-P., Carra-Dalière, C., Casez, O., Chamouard, J.-M., Chassande, B., Chataignier, P., Chbicheb, M., Chenet, A., Ciron, J., Clavelou, P., Cohen, M., Colamarino, R., Collongues, N., Coman, I., Corail, P.-R., Courtois, S., Coustans, M., Creange, A., Creisson, E., Daluzeau, N., Davenas, C., De Seze, J., Debouverie, M., Depaz, R., Derache, N., Divio, L., Douay, X., Dulau, C., Durand-Dubief, F., Edan, G., Elias, Z., Fagniez, O., Faucher, M., Faucheux, J.-M., Fournier, M., Gagneux-Brunon, A., Gaida, P., Galli, P., Gallien, P., Gaudelus, J., Gault, D., Gayou, A., Genevray, M., Gentil, A., Gere, J., Gignoux, L., Giroux, M., Givron, P., Gout, O., Grimaud, J., Guennoc, A.-M., Hadhoum, N., Hautecoeur, P., Heinzlef, O., Jaeger, M., Jeannin, S., Kremer, L., Kwiatkowski, A., Labauge, P., Labeyrie, C., Lachaud, S., Laffont, I., Lanctin-Garcia, C., Lannoy, J., Lanotte, L., Laplaud, D., Latombe, D., Lauxerois, M., Le Page, E., Lebrun-Frenay, C., Lejeune, P., Lejoyeux, P., Lemonnier, B., Leray, E., Loche, C.-M., Louapre, C., Lubetzki, C., Maarouf, A., Mada, B., Magy, L., Maillart, E., Manchon, E., Marignier, R., Marque, P., Mathey, G., Maurousset, A., Mekies, C., Merienne, M., Michel, L., Milor, A.-M., Moisset, X., Montcuquet, A., Moreau, T., Morel, N., Moussa, M., Naudillon, J.-P., Normand, M., Olive, P., Ouallet, J.-C., Outteryck, O., Pacault, C., Papeix, C., Patry, I., Peaureaux, D., Pelletier, J., Pichon, B., Pittion, S., Planque, E., Pouget, M.-C., Pourcher, V., Radot, C., Robert, I., Rocher, F., Ruet, A., Saint-Val, C., Salle, J.-Y., Salmon, A., Sartori, E., Schaeffer, S., Stankhof, B., Taithe, F., Thouvenot, E., Tizon, C., Tourbah, A., Tourniaire, P., Vaillant, M., Vermersch, P., Vidil, S., Wahab, A., Warter, M.-H., Wiertlewski, S., Wiplosz, B., Wittwer, B., Zaenker, C., Zephir, H., Lebrun, C., and Vukusic, S.

Published
2019
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10. Description du risque infectieux chez les patients avec hypogammaglobulinémie acquise dans le cadre d’une maladie auto-immune et initiant ou poursuivant un traitement par rituximab

Author

Boumaza, X., primary, Lafaurie, M., additional, Treiner, E., additional, Walter, O., additional, Pugnet, G., additional, Martin-Blondel, G., additional, Biotti, D., additional, Ciron, J., additional, Moulis, G., additional, Constantin, A., additional, Tauber, M., additional, Renaudineau, Y., additional, Chauveau, D., additional, and Sailler, L., additional

Published
2022
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11. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis.

Author

Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., Kalincik T., Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., and Kalincik T.

Abstract

OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHOD(S): This was a retrospective cohort study from two large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12-months were included in the analysis. The primary study outcome was annualised relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULT(S): 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for seven therapies. Annualised rates of relapse (ARR) started to increase 2-months after natalizumab cessation (month 2-4 ARR, 95% confidence interval): 0.47, 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89), and stabilised faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01-0.29). Magnitude of disease reactivation for other therapies was low, but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were higher relapse rate in the year before cessation, female sex, younger age and higher EDSS. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95%CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). CONCLUSION(S): The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different t

Published
2022

12. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

Lefort, M, Sharmin, S, Andersen, JB, Vukusic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, De Seze, J, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun-Frenay, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanche, JP, Maurousset, A, Ben Nasr, H, Hankiewicz, K, Pottier, C, Maubeuge, N, Nifle, C, Laplaud, DA, Horakova, D, Dimitri-Boulos, D, Havrdova, EK, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Grand'Maison, F, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Shaygannejad, V, Prevost, J, Maimone, D, Skibina, O, Buzzard, K, Van der Walt, A, Karabudak, R, Van Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Koch-Henriksen, N, Sellebjerg, F, Soerensen, PS, Christensen, CCH, Rasmussen, P, Jensen, MB, Frederiksen, JL, Bramow, S, Mathiesen, HK, Schreiber, K, Butzkueven, H, Magyari, M, Kalincik, T, Leray, E, Lefort, M, Sharmin, S, Andersen, JB, Vukusic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, De Seze, J, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun-Frenay, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanche, JP, Maurousset, A, Ben Nasr, H, Hankiewicz, K, Pottier, C, Maubeuge, N, Nifle, C, Laplaud, DA, Horakova, D, Dimitri-Boulos, D, Havrdova, EK, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Grand'Maison, F, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Shaygannejad, V, Prevost, J, Maimone, D, Skibina, O, Buzzard, K, Van der Walt, A, Karabudak, R, Van Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Koch-Henriksen, N, Sellebjerg, F, Soerensen, PS, Christensen, CCH, Rasmussen, P, Jensen, MB, Frederiksen, JL, Bramow, S, Mathiesen, HK, Schreiber, K, Butzkueven, H, Magyari, M, Kalincik, T, and Leray, E

Abstract

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is ful

Published
2022

13. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis

Author

Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, Kalincik, T, Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, and Kalincik, T

Abstract

BACKGROUND AND OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHODS: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULTS: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). DISCUSSION: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued di

Published
2022

14. Impact of methodological choices in comparative effectiveness studies:application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

Lefort, M., Sharmin, S., Andersen, J. B., Vukusic, S., Casey, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., De Sèze, J., Maillart, E., Zephir, H., Labauge, P., Defer, G., Lebrun-Frenay, C., Moreau, T., Berger, E., Clavelou, P., Pelletier, J., Stankoff, B., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Wahab, A., Camdessanché, J. P., Maurousset, A., Ben Nasr, H., Hankiewicz, K., Pottier, C., Maubeuge, N., Dimitri-Boulos, D., Nifle, C., Laplaud, D. A., Horakova, D., Havrdova, E. K., Alroughani, R., Izquierdo, G., Eichau, S., Ozakbas, S., Patti, F., Onofrj, M., Lugaresi, A., Terzi, M., Grammond, P., Grand’Maison, F., Yamout, B., Prat, A., Girard, M., Duquette, P., Boz, C., Trojano, M., McCombe, P., Slee, M., Lechner-Scott, J., Turkoglu, R., Sola, P., Ferraro, D., Granella, F., Shaygannejad, V., Prevost, J., Maimone, D., Skibina, O., Buzzard, K., Van der Walt, A., Karabudak, R., Van Wijmeersch, B., Csepany, T., Spitaleri, D., Vucic, S., Koch-Henriksen, N., Sellebjerg, F., Soerensen, P. S., Hilt Christensen, C. C., Rasmussen, P. V., Jensen, M. B., Frederiksen, J. L., Bramow, S., Mathiesen, H. K., Schreiber, K. I., Butzkueven, H., Magyari, M., Kalincik, T., Leray, E., Lefort, M., Sharmin, S., Andersen, J. B., Vukusic, S., Casey, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., De Sèze, J., Maillart, E., Zephir, H., Labauge, P., Defer, G., Lebrun-Frenay, C., Moreau, T., Berger, E., Clavelou, P., Pelletier, J., Stankoff, B., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Wahab, A., Camdessanché, J. P., Maurousset, A., Ben Nasr, H., Hankiewicz, K., Pottier, C., Maubeuge, N., Dimitri-Boulos, D., Nifle, C., Laplaud, D. A., Horakova, D., Havrdova, E. K., Alroughani, R., Izquierdo, G., Eichau, S., Ozakbas, S., Patti, F., Onofrj, M., Lugaresi, A., Terzi, M., Grammond, P., Grand’Maison, F., Yamout, B., Prat, A., Girard, M., Duquette, P., Boz, C., Trojano, M., McCombe, P., Slee, M., Lechner-Scott, J., Turkoglu, R., Sola, P., Ferraro, D., Granella, F., Shaygannejad, V., Prevost, J., Maimone, D., Skibina, O., Buzzard, K., Van der Walt, A., Karabudak, R., Van Wijmeersch, B., Csepany, T., Spitaleri, D., Vucic, S., Koch-Henriksen, N., Sellebjerg, F., Soerensen, P. S., Hilt Christensen, C. C., Rasmussen, P. V., Jensen, M. B., Frederiksen, J. L., Bramow, S., Mathiesen, H. K., Schreiber, K. I., Butzkueven, H., Magyari, M., Kalincik, T., and Leray, E.

Abstract

Background: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results: Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is

Published
2022

15. POS1178 PRESCRIBING RITUXIMAB IN PATIENTS WITH AUTO-IMMUNE DISEASES AND ACQUIRED HYPOGAMMAGLOBULINEMIA: DESCRIPTION OF THE RISK OF SEVERE INFECTION IN 121 PATIENTS BEFORE THE SARS-Cov2 ERA

Author

Xavier, B., primary, Lafaurie, M., additional, Treiner, E., additional, Walter, O., additional, Pugnet, G., additional, Martin-Blondel, G., additional, Biotti, D., additional, Ciron, J., additional, Moulis, G., additional, Constantin, A., additional, Renaudineau, Y., additional, Chauveau, D., additional, and Sailler, L., additional

Published
2022
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19. Improving the decision to switch from first to second-line therapy in MS: a dynamic scoring system

Author

Sabathe, C., Casey, Romain, Vukusic, S., Leray, Emmanuelle, Mathey, G., de Seze, J., Ciron, J., Wiertlewski, S., Ruet, A., Pelletier, J., Zephir, H., Michel, L., Lebrun-Frenay, C., Moisset, X., Thouvenot, Eric, Camdessanche, J. -P., Bakchine, Serge, Stankoff, B., Al Khedr, A., Cabre, P., Maillart, E., Berger, E., Heinzlef, O., Hankiewicz, K., Moreau, T., Gout, O., Bourre, B., Wahab, A., Labauge, Pierre, Montcuquet, A., Defer, G., Maurousset, A., Maubeuge, N., Dalia, D. Boulos, Ben Nasr, H., Nifle, C., Casez, O., Laplaud, D. -A., Foucher, yohann, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), 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 Bordeaux (UB), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 Amiens-Picardie, CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHI Poissy-Saint-Germain, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Fondation Ophtalmologique Adolphe de Rotschild, CHU Rouen, Normandie Université (NU), CHU Henri Mondor [Créteil], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Hôpital Sud Francilien Corbeil Essonne, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire de Génétique Chromosomique [CHU de Grenoble], CHU Grenoble, Agence Nationale de la Recherche French National Research Agency (ANR) uropean Commission [ANR-10COHO-002], Fond de dotation de l'Universite de Nantes, Foundation EDMUS, ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, CHU Toulouse [Toulouse], Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de 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 [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), CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Meeting Abstract 035

Published
2021
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20. Infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Papeix, C., primary, Donze, C., additional, Lebrun-Frénay, C., additional, Papeix, C., additional, Donzé, C., additional, Laplaud, D., additional, Thouvenot, E., additional, Ayrignac, X., additional, Pourcher-Martinez, V., additional, Zéphir, H., additional, de Seze, J., additional, Michel, L., additional, Bensa, C., additional, Cara-Dalliere, C., additional, Guen-noc, A.M., additional, Casez, O., additional, Maarouf, A., additional, Bourre, B., additional, Kwiatkowski, A., additional, Cohen, M., additional, Maillart, E., additional, Collongues, N., additional, Louapre, C., additional, Androdias, G., additional, Guegen, A., additional, Audoin, B., additional, Mattey, G., additional, Bernady, P., additional, Faucheux, J.M., additional, Labauge, P., additional, Meckies, C., additional, Stankoff, B., additional, Tourniaire, P., additional, Dinh, A., additional, Guennoc, A.M., additional, Durnad-Dubief, F., additional, Wiertlewski, S., additional, Derache, N., additional, Le page, E., additional, Pittion, S., additional, Vukusic, S., additional, Clavelou, P., additional, Heinzlef, O., additional, Colamarino, R., additional, Planque, E., additional, Rico, A., additional, Sheiber nogueira, C., additional, de Seze, M., additional, Ciron, J., additional, Alchaar, H., additional, Bensmail, D., additional, Biotti, D., additional, Branger, P., additional, Brochet, B., additional, Castan, B., additional, Creange, A., additional, Creisson, E., additional, DeBroucker, T., additional, Depaz, R., additional, Douay, X., additional, Dulau, C., additional, Faucher, M., additional, Fournier, M., additional, Fromont, A., additional, Gallien, P., additional, Gout, O., additional, Grimaud, J., additional, Hervé, Y., additional, Kerbrat, A., additional, Kremer, L., additional, Lanotte, L., additional, Magy, L., additional, Mania, A., additional, Maurousset, A., additional, Moisset, X., additional, Montcuquet, A., additional, Moreau, T., additional, Morel, N., additional, Patry, I., additional, Peaureaux, D., additional, Pouget, M.C., additional, Ruet, A., additional, Saint-Val, C., additional, Stahl, J.P., additional, Taithe, F., additional, Tattevin, P., additional, Vaillant, M., additional, and Vuoto, F., additional

Published
2021
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21. DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France: a pooled analysis from Italy and France

Author

Sormani, M. (Maria Pia) P. (P), Salvetti, M. (Marco), Labauge, P. (Pierre), Schiavetti, I. (Irene), Zephir, H. (Helene), Carmisciano, L. (Luca), Bensa, C. (Caroline), De Rossi, N. (Nicola), Pelletier, J. (Jean), Cordioli, C. (Cinzia), Vukusic, S. (Sandra), Moiola, L. (Lucia), Kerschen, P. (Philippe), Radaelli, M. (Marta), Théaudin, M. (Marie), Immovilli, P. (Paolo), Casez, O. (Olivier), Capobianco, M. (Marco), Ciron, J. (Jonathan), Trojano, M. (Maria), Stankoff, B. (Bruno), Créange, A. (Alain), Tedeschi, G. (Gioacchino), Clavelou, P. (Pierre), Comi, G. (Giancarlo), Thouvenot, E. (Eric), Battaglia, M. (Mario) A. (Alberto), Moreau, T. (Thibault), Patti, F. (Francesco), De Sèze, J. (Jérôme), Louapre, C. (Celine), and Musc

Subjects
Aucun
Abstract

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p

Published
2021

22. Eur J Neurol

Author

Deschamps, R. (Romain), Pique, J. (Julie), Ayrignac, X. (Xavier), Collongues, N. (Nicolas), Audoin, B. (Bertrand), Zéphir, H. (Hélène), Ciron, J. (Jonathan), Cohen, M. (Mikael), Aboab, J. (Jennifer), Mathey, G. (Guillaume), Derache, N. (Nathalie), Laplaud, D. (David), Thouvenot, E. (Eric), Bourre, B. (Bertrand), Ruet, A. (Aurélie), Durand-Dubief, F. (Françoise), Touitou, V. (Valérie), Vignal-Clermont, C. (Catherine), Papeix, C. (Caroline), Gout, O. (Olivier), Marignier, R. (Romain), and Maillart, E. (Elisabeth)

Subjects
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]
Abstract

BACKGROUND AND OBJECTIVE: The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a matter of debate. Our aim was to assess the long-term outcomes of patients with MOGAD. METHODS: We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG-IgG) and who had clinical follow-up of at least 8 years from their first episode. RESULTS: Sixty-one patients (median [range] age at onset 27 [3-69] years), with a median (mean; range) follow-up of 177 (212.8; 98-657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0-7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long-term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found. CONCLUSION: Overall long-term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon.

Published
2021

23. The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies

Author

Andersen, JB, Sharmin, S, Lefort, M, Koch-Henriksen, N, Sellebjerg, F, Sorensen, PS, Christensen, CCH, Rasmussen, P, Jensen, MB, Frederiksen, JL, Bramow, S, Mathiesen, HK, Schreiber, K, Horakova, D, Havrdova, EK, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Maison, FG, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Shaygannejad, V, Prevost, J, Skibina, O, Solaro, C, Karabudak, R, Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, Seze, JD, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanche, J-P, Marousset, A, Patry, I, Hankiewicz, K, Pottier, C, Maubeuge, N, Labeyrie, C, Nifle, C, Leray, E, Laplaud, DA, Butzkueven, H, Kalincik, T, Vukusic, S, Magyari, M, Andersen, JB, Sharmin, S, Lefort, M, Koch-Henriksen, N, Sellebjerg, F, Sorensen, PS, Christensen, CCH, Rasmussen, P, Jensen, MB, Frederiksen, JL, Bramow, S, Mathiesen, HK, Schreiber, K, Horakova, D, Havrdova, EK, Alroughani, R, Izquierdo, G, Eichau, S, Ozakbas, S, Patti, F, Onofrj, M, Lugaresi, A, Terzi, M, Grammond, P, Maison, FG, Yamout, B, Prat, A, Girard, M, Duquette, P, Boz, C, Trojano, M, McCombe, P, Slee, M, Lechner-Scott, J, Turkoglu, R, Sola, P, Ferraro, D, Granella, F, Shaygannejad, V, Prevost, J, Skibina, O, Solaro, C, Karabudak, R, Wijmeersch, B, Csepany, T, Spitaleri, D, Vucic, S, Casey, R, Debouverie, M, Edan, G, Ciron, J, Ruet, A, Seze, JD, Maillart, E, Zephir, H, Labauge, P, Defer, G, Lebrun, C, Moreau, T, Berger, E, Clavelou, P, Pelletier, J, Stankoff, B, Gout, O, Thouvenot, E, Heinzlef, O, Al-Khedr, A, Bourre, B, Casez, O, Cabre, P, Montcuquet, A, Wahab, A, Camdessanche, J-P, Marousset, A, Patry, I, Hankiewicz, K, Pottier, C, Maubeuge, N, Labeyrie, C, Nifle, C, Leray, E, Laplaud, DA, Butzkueven, H, Kalincik, T, Vukusic, S, and Magyari, M

Abstract

BACKGROUND: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. METHODS: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. RESULTS: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. CONCLUSION: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Published
2021

24. Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event

Author

Lebrun-Frenay, C., Kantarci, O., Siva, A., Sormani, M. P., Pelletier, D., Okuda, D. T., Azevedo, C., Amato, M. P., Bensa, C., Berger, E., Brochet, B., Ciron, J., Cohen, M., Inglese, M., Keegan, B. M., Labauge, P., Laplaud, D. -A., Le Page, E., Louapre, C., Makhani, N., Mathey, G., Mondot, L., Montalban, X., Pelletier, J., de Seze, J., Destefano, N., Thouvenot, E., Tintore, M., Tutuncuoglu, M., Uygunoglu, U., Vermersch, P., Weinshenker, B., and Zeydan, B.

Subjects
0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, Journal Club, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, medicine, Humans, Young adult, Child, Event (probability theory), Aged, medicine.diagnostic_test, Clinical events, business.industry, Proportional hazards model, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Demyelinating Diseases, Female, Magnetic Resonance Imaging, Disease Progression, 030104 developmental biology, Risk Estimate, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10-year, multinational, retrospectively identified RIS dataset. Methods RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models. Results Additional follow-up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11-74 years), with a median clinical follow-up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium-enhanced lesions during follow-up was also associated with the risk of a seminal event. The reason for MRI and gadolinium-enhancing lesions at baseline did not influence the risk of a subsequent clinical event. Interpretation Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407-417.

Published
2020

25. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults

Author

Cobo-Calvo, A., Ruiz, A., Maillart, E., Audoin, B., Zephir, H., Bourre, B., Ciron, J., Collongues, N., Brassat, D., Cotton, F., Papeix, C., Durand-Dubief, F., Laplaud, D., Deschamps, R., Cohen, M., Biotti, D., Ayrignac, X., Tilikete, C., Thouvenot, E., Brochet, B., Dulau, C., Moreau, T., Tourbah, A., Lebranchu, P., Michel, L., Lebrun-Frenay, C., Montcuquet, A., Mathey, G., Debouverie, M., Pelletier, J., Derache, N., Coustans, M., Rollot, F., De Seze, J., Vukusic, S., Marignier, R., Casey, D. R., Maze, D. M., Olaiz, D. J., Frangoulis, D. B., Debard, N., Vukusic, P. S., Zorila, D. C., Debouverie, P. M., Guillemin, P. F., Mathey, D. G., Ziegler, A., Edan, P. G., Le Page, D. E., Leray, D. E., Muraz, R., Brassat, P. D., Clanet, P. M., Peaureaux-Averseng, D. D., Dewas, C., Brochet, P. B., Ouallet, D. J., Ruet, D. A., Kounkou, K. K., De Seze, P. J., Collongues, D. N., Berthe, C., Vermersch, P. P., Hautecoeur, P. P., Deruelle, F., Papeix, D. C., Maillard, D. E., Lubetzki, P. C., Lebrun-Frenay, D. C., Cohen, D. M., Callier, C., Derache, D. N., Droulon, K., Labauge, P. P., Ayrignac, D. X., Carra-Dalliere, D. C., Pinna, F., Moreau, P. T., Fromont, D. A., Protin, A., Michel, D. L., Wiertlewski, D. S., Jousset, N., Berger, D. E., Chamard-Witkowski, D. L., Bereau, D. M., Cappe, C., Clavelou, P. P., Taithe, D. F., Moisset, D. X., Dumont, E., Pelletier, P. J., Audoin, P. B., Rico-Lamy, D. A., Di Lelio, B., Castelnovo, D. G., Stankoff, P. B., Giannesini, D. C., Heinzlef, D. O., Fagniez, D. O., Laage, D. C., Bourre, D. B., Lefaucheur, D. R., Maltete, D. D., Vimont, C., Al Khedr, D. A., Sehaki, S., Gout, D. O., Bensa, D. C., Cabre, P. P., Kasonde, D. I., Galli, P., Magy, P. L., Montcuquet, D. A., Nicol, M., Casez, D. O., Vaillant, D. M., Diop Kane, M., Camdessanche, P. J., Visneux, V., Guennnoc, D. A., Beltran, D. S., Meunier, G., Creange, P. A., Ayache, D. S., Abdellaoui, D. M., Pottier, D. C., Slesari, D. I., Sampaio, M., Deburghraeve?, D. V., Le Port, D., Ciron, D. J., Neau, P. J., Rabois, E., Labeyrie, D. C., Patry, D. I., Lescieux, E., Nifle, D. C., Servan, D. J., Pico, P. F., Chatagner, V., Camus-Jacqmin, D. M., Henry, D. C., Bottin, D. L., Castex, C., Diallo, S. S., Brisset, J. C., Cervenansky, F., Commovick, O., Defer, P. G., Durand-Dubief, D. F., Guttmann, P. C., Tourbah, P. A., Lifticariu, D. C., Constans, D. J., Tanguy, D. J., Dousset, P. V., Tourdias, D. T., Dardel, D. P., Oesterle, D. H., Gonin, D. S., Ricolfi, D. F., Grand, D. S., Krainik, D. A., Boncoeur-Martel, D. M., Ameli, D. R., Bonhomme, D. G., Cotton, P. F., Roch, D. J., Sappey-Marinier, D. D., Brunel, H., Coze, S., Girard, Nicolas, Lehmann, P., Ranjeva, P. J., Menjot De Champfleur, Nicolas, Anxionnat, P. R., Desal, D. H., Mondot, D. L., Savatovsky, D. J., Galanaud, P. D., Pyatigorskaya, D. N., Guillevin, D. R., Pierot, D. L., Barillot, D. C., Ferre, D. J., Bannier, E., Gerardin, D. E., Boutet, D. C., Kremer, D. S., Armspach, P. J., Berry, P. I., Bonneville, P. F., Dufay, N., Zephir, D. H., Gele, P., Marignier, D. R., Fiard, G., Lehmann, S., Lommazi, S., Laplaud, P. D., Gallot, G., Thouvenot, P. E., Fontaine, P. B., Rebeix, I., Desille-Dugast, M., CHU Pitié-Salpêtrière [APHP], 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), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de Hautepierre [Strasbourg], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Department of Neurology, CHU Lyon, Centre Hospitalier Universitaire de Nice (CHU Nice), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Reims (CHU Reims), Observatoire astronomique de Strasbourg (ObAS), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), The Functional Electrical Neuroimaging Laboratory, Université de Lausanne (UNIL), Department of Economics, École Polytechnique, Palaiseau Cedex, 91128, France, affiliation inconnue, Alimentation et sciences sociales (ALISS), Institut National de la Recherche Agronomique (INRA), CHU Marseille, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, ISL, Laboratoire Charles Coulomb (L2C), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Instituto de Tecnologia Ceramica, Universitat Jaume I, CHU Grenoble, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, medicine.medical_specialty, Visual acuity, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, business.industry, Hazard ratio, Encephalopathy, Myelitis, Retrospective cohort study, Lower risk, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, Optic neuritis, Neurology (clinical), medicine.symptom, 10. No inequality, business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Survival analysis
Abstract

ObjectiveTo describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis.MethodsClinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included.ResultsMedian age at onset was 36.46 (range 18.0–76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26–0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22–0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07–0.72). Finally, MOG-Ab titers were higher at relapse than in remission (p = 0.009).ConclusionIn adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients.

Published
2018
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26. Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI

Author

Roca, P., primary, Attye, A., additional, Colas, L., additional, Tucholka, A., additional, Rubini, P., additional, Cackowski, S., additional, Ding, J., additional, Budzik, J.-F., additional, Renard, F., additional, Doyle, S., additional, Barbier, E.L., additional, Bousaid, I., additional, Casey, R., additional, Vukusic, S., additional, Lassau, N., additional, Verclytte, S., additional, Cotton, F., additional, Brochet, B., additional, De Sèze, J., additional, Douek, P., additional, Guillemin, F., additional, Laplaud, D., additional, Lebrun-Frenay, C., additional, Mansuy, L., additional, Moreau, T., additional, Olaiz, J., additional, Pelletier, J., additional, Rigaud-Bully, C., additional, Stankoff, B., additional, Marignier, R., additional, Debouverie, M., additional, Edan, G., additional, Ciron, J., additional, Ruet, A., additional, Collongues, N., additional, Lubetzki, C., additional, Vermersch, P., additional, Labauge, P., additional, Defer, G., additional, Cohen, M., additional, Fromont, A., additional, Wiertlewsky, S., additional, Berger, E., additional, Clavelou, P., additional, Audoin, B., additional, Giannesini, C., additional, Gout, O., additional, Thouvenot, E., additional, Heinzlef, O., additional, Al-Khedr, A., additional, Bourre, B., additional, Casez, O., additional, Cabre, P., additional, Montcuquet, A., additional, Créange, A., additional, Camdessanché, J.-P., additional, Faure, J., additional, Maurousset, A., additional, Patry, I., additional, Hankiewicz, K., additional, Pottier, C., additional, Maubeuge, N., additional, Labeyrie, C., additional, Nifle, C., additional, Ameli, R., additional, Anxionnat, R., additional, Bannier, E., additional, Barillot, C., additional, Ben Salem, D., additional, Boncoeur-Martel, M.-P., additional, Bonneville, F., additional, Boutet, C., additional, Brisset, J.-C., additional, Cervenanski, F., additional, Claise, B., additional, Commowick, O., additional, Constans, J.-M., additional, Dardel, P., additional, Desal, H., additional, Dousset, Vincent, additional, Durand-Dubief, F., additional, Ferre, J.-C., additional, Gerardin, E., additional, Glattard, T., additional, Grand, S., additional, Grenier, T., additional, Guillevin, R., additional, Guttmann, C., additional, Krainik, A., additional, Kremer, S., additional, Lion, S., additional, Menjot de Champfleur, N., additional, Mondot, L., additional, Outteryck, O., additional, Pyatigorskaya, N., additional, Pruvo, J.-P., additional, Rabaste, S., additional, Ranjeva, J.-P., additional, Roch, J.-A., additional, Sadik, J.C., additional, Sappey-Marinier, D., additional, Savatovsky, J., additional, Tanguy, J.-Y., additional, Tourbah, A., additional, and Tourdias, T., additional

Published
2020
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29. New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

Author

Brisset, Jean-Christophe, primary, Kremer, Stephane, additional, Hannoun, Salem, additional, Bonneville, Fabrice, additional, Durand-Dubief, Francoise, additional, Tourdias, Thomas, additional, Barillot, Christian, additional, Guttmann, Charles, additional, Vukusic, Sandra, additional, Dousset, Vincent, additional, Cotton, Francois, additional, Ameli, R., additional, Anxionnat, R., additional, Audoin, B., additional, Attye, A., additional, Bannier, E., additional, Barillot, C., additional, Ben Salem, D., additional, Boncoeur-Martel, M.-P., additional, Bonhomme, G., additional, Bonneville, F., additional, Boutet, C., additional, Brisset, J.C., additional, Cervenanski, F., additional, Claise, B., additional, Commowick, O., additional, Constans, J.-M., additional, Cotton, F., additional, Dardel, P., additional, Desal, H., additional, Dousset, V., additional, Durand-Dubief, F., additional, Ferre, J.-C., additional, Gaultier, A., additional, Gerardin, E., additional, Glattard, T., additional, Grand, S., additional, Grenier, T., additional, Guillevin, R., additional, Guttmann, C., additional, Krainik, A., additional, Kremer, S., additional, Lion, S., additional, Champfleur, N. Menjot De, additional, Mondot, L., additional, Outteryck, O., additional, Pyatigorskaya, N., additional, Pruvo, J.-P., additional, Rabaste, S., additional, Ranjeva, J.-P., additional, Roch, J.-A., additional, Sadik, J.-C., additional, Sappey-Marinier, D., additional, Savatovsky, J., additional, Stankoff, B., additional, Tanguy, J.-Y., additional, Tourbah, A., additional, Tourdias, T., additional, Brochet, B., additional, Casey, R., additional, De Sèze, J., additional, Douek, P., additional, Guillemin, F., additional, Laplaud, D., additional, Lebrun-Frenay, C., additional, Mansuy, L., additional, Moreau, T., additional, Olaiz, J., additional, Pelletier, J., additional, Rigaud-Bully, C., additional, Vukusic, S., additional, Debouverie, M., additional, Edan, G., additional, Ciron, J., additional, Lubetzki, C., additional, Vermersch, P., additional, Labauge, P., additional, Defer, G., additional, Berger, E., additional, Clavelou, P., additional, Gout, O., additional, Thouvenot, E., additional, Heinzlef, O., additional, Al-Khedr, A., additional, Bourre, B., additional, Casez, O., additional, Cabre, P., additional, Montcuquet, A., additional, Créange, A., additional, Camdessanché, J.-P., additional, Bakchine, S., additional, Maurousset, A., additional, Patry, I., additional, De Broucker, T., additional, Pottier, C., additional, Neau, J.-P., additional, Labeyrie, C., additional, and Nifle, C., additional

Published
2020
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30. Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

Author

Bigaut, K, primary, Lambert, C, additional, Kremer, L, additional, Lebrun, C, additional, Cohen, M, additional, Ciron, J, additional, Bourre, B, additional, Créange, A, additional, Kerschen, P, additional, Montcuquet, A, additional, Carra-Dalliere, C, additional, Ayrignac, X, additional, Labauge, P, additional, de Seze, J, additional, and Collongues, N, additional

Published
2020
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31. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

Lebrun, C., primary, Vukusic, S., additional, Abadie, V., additional, Achour, C., additional, Ader, F., additional, Alchaar, H., additional, Alkhedr, A., additional, Andreux, F., additional, Androdias, G., additional, Arjmand, R., additional, Audoin, B., additional, Audry, D., additional, Aufauvre, D., additional, Autreaux, C., additional, Ayrignac, X., additional, Bailbe, M., additional, Benazet, M., additional, Bensa, C., additional, Bensmail, D., additional, Berger, E., additional, Bernady, P., additional, Bertagna, Y., additional, Biotti, D., additional, Blanchard-Dauphin, A., additional, Bonenfant, J., additional, Bonnan, M., additional, Bonnemain, B., additional, Borgel, F., additional, Botelho-Nevers, E., additional, Boucly, S., additional, Bourre, B., additional, Boutière, C., additional, Branger, P., additional, Brassat, D., additional, Bresch, S., additional, Breuil, V., additional, Brochet, B., additional, Brugeilles, H., additional, Bugnon, P., additional, Cabre, P., additional, Camdessanché, J.-P., additional, Carra-Dalière, C., additional, Casez, O., additional, Chamouard, J.-M., additional, Chassande, B., additional, Chataignier, P., additional, Chbicheb, M., additional, Chenet, A., additional, Ciron, J., additional, Clavelou, P., additional, Cohen, M., additional, Colamarino, R., additional, Collongues, N., additional, Coman, I., additional, Corail, P.-R., additional, Courtois, S., additional, Coustans, M., additional, Creange, A., additional, Creisson, E., additional, Daluzeau, N., additional, Davenas, C., additional, De Seze, J., additional, Debouverie, M., additional, Depaz, R., additional, Derache, N., additional, Divio, L., additional, Douay, X., additional, Dulau, C., additional, Durand-Dubief, F., additional, Edan, G., additional, Elias, Z., additional, Fagniez, O., additional, Faucher, M., additional, Faucheux, J.-M., additional, Fournier, M., additional, Gagneux-Brunon, A., additional, Gaida, P., additional, Galli, P., additional, Gallien, P., additional, Gaudelus, J., additional, Gault, D., additional, Gayou, A., additional, Genevray, M., additional, Gentil, A., additional, Gere, J., additional, Gignoux, L., additional, Giroux, M., additional, Givron, P., additional, Gout, O., additional, Grimaud, J., additional, Guennoc, A.-M., additional, Hadhoum, N., additional, Hautecoeur, P., additional, Heinzlef, O., additional, Jaeger, M., additional, Jeannin, S., additional, Kremer, L., additional, Kwiatkowski, A., additional, Labauge, P., additional, Labeyrie, C., additional, Lachaud, S., additional, Laffont, I., additional, Lanctin-Garcia, C., additional, Lannoy, J., additional, Lanotte, L., additional, Laplaud, D., additional, Latombe, D., additional, Lauxerois, M., additional, Le Page, E., additional, Lebrun-Frenay, C., additional, Lejeune, P., additional, Lejoyeux, P., additional, Lemonnier, B., additional, Leray, E., additional, Loche, C.-M., additional, Louapre, C., additional, Lubetzki, C., additional, Maarouf, A., additional, Mada, B., additional, Magy, L., additional, Maillart, E., additional, Manchon, E., additional, Marignier, R., additional, Marque, P., additional, Mathey, G., additional, Maurousset, A., additional, Mekies, C., additional, Merienne, M., additional, Michel, L., additional, Milor, A.-M., additional, Moisset, X., additional, Montcuquet, A., additional, Moreau, T., additional, Morel, N., additional, Moussa, M., additional, Naudillon, J.-P., additional, Normand, M., additional, Olive, P., additional, Ouallet, J.-C., additional, Outteryck, O., additional, Pacault, C., additional, Papeix, C., additional, Patry, I., additional, Peaureaux, D., additional, Pelletier, J., additional, Pichon, B., additional, Pittion, S., additional, Planque, E., additional, Pouget, M.-C., additional, Pourcher, V., additional, Radot, C., additional, Robert, I., additional, Rocher, F., additional, Ruet, A., additional, Saint-Val, C., additional, Salle, J.-Y., additional, Salmon, A., additional, Sartori, E., additional, Schaeffer, S., additional, Stankhof, B., additional, Taithe, F., additional, Thouvenot, E., additional, Tizon, C., additional, Tourbah, A., additional, Tourniaire, P., additional, Vaillant, M., additional, Vermersch, P., additional, Vidil, S., additional, Wahab, A., additional, Warter, M.-H., additional, Wiertlewski, S., additional, Wiplosz, B., additional, Wittwer, B., additional, Zaenker, C., additional, and Zephir, H., additional

Published
2019
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32. Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders.

Author

Bigaut, K, Lambert, C, Kremer, L, Lebrun, C, Cohen, M, Ciron, J, Bourre, B, Créange, A, Kerschen, P, Montcuquet, A, Carra-Dalliere, C, Ayrignac, X, Labauge, P, de Seze, J, and Collongues, N

Subjects
NEUROMYELITIS optica, MYELITIS, MULTIPLE sclerosis, MULTIPLE comparisons (Statistics), TRANSVERSE myelitis, DISEASES
Abstract

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis. [ABSTRACT FROM AUTHOR]

Published
2021
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33. Efficacité comparée du Teriflunomide et du Dimethyl-Fumarate : une étude observationnelle française multicentrique

Author

Laplaud, D.-A., primary, Barbin, L., additional, Casey, R., additional, Debouverie, M., additional, Vukusic, S., additional, Labauge, P., additional, Brassat, D., additional, Wiertlewski, S., additional, De Seze, J., additional, Edan, G., additional, Brochet, B., additional, Moreau, T., additional, Berger, E., additional, Clavelou, P., additional, Castelnovo, G., additional, Ciron, J., additional, Pelletier, J., additional, Bourre, B., additional, Lubetzki, C., additional, Al Khedr, A., additional, Vermersch, P., additional, Lebrun-Frenay, C., additional, Defer, G., additional, Tourbah, A., additional, Camdessanche, J.-P., additional, Stankoff, B., additional, Labeyrie, C., additional, Patry, I., additional, Creange, A., additional, Gout, O., additional, Heinzlef, O., additional, Casez, O., additional, Magy, L., additional, Guennoc, A.-M., additional, De Broucker, T., additional, Nifle, C., additional, Dupel-Pottier, C., additional, Leray, E., additional, Rollot, F., additional, and Foucher, Y., additional

Published
2018
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36. Sclerosi multipla: aspetti evolutivi e prognostici

Author

Ciron, J.

Abstract

L’evoluzione e la prognosi dei pazienti affetti da sclerosi multipla sono difficili da prevedere su scala individuale. A livello di gruppo, sono fortemente condizionate dal tipo di forma progressiva della patologia, con le attuali terapie che risultano efficaci nel prevenire un’attività infiammatoria e quindi un peggioramento legato a tale attività infiammatoria, mentre sono poco efficaci nel prevenire un peggioramento indipendente dall’attività infiammatoria. Lo studio di coorti recenti che hanno beneficiato di trattamenti di base convalidati ha rivelato un miglioramento della prognosi rispetto alle coorti storiche non trattate. Le forme recidivanti-remittenti hanno un’evoluzione a breve termine dipendente essenzialmente dal verificarsi di riacutizzazioni e dai loro postumi, anche se sempre più lavori documentano anche allo stadio iniziale di queste forme progressive la possibilità di un peggioramento indipendente dall’attività infiammatoria della patologia. Il rischio a lungo termine è quello di un’evoluzione verso una forma secondariamente progressiva. Le forme primarie progressive hanno un’evoluzione più peggiorativa, dal momento che l’aggravamento è solo debolmente legato all’attività infiammatoria e quindi poco influenzato dagli attuali trattamenti di base della patologia. Indipendentemente dalla forma progressiva della patologia, sono stati identificati numerosi fattori prognostici clinici, biologici e radiologici. Alcuni sono disponibili fin dalla diagnosi della patologia, mentre altri vengono valutati durante il follow-up, in particolare la persistenza dell’attività infiammatoria della patologia nonostante un trattamento di fondo.

Published
2024
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39. Disease reactivation after cessation of disease-modifying therapy in relapsing-remitting multiple sclerosis

Author

Izanne Roos, Malpas, C., Leray, E., Casey, R., Horakova, D., Havrdova, E. Kubala, Debouverie, M., Patti, F., Seze, J., Izquierdo, G., Eichau, S., Edan, G., Prat, A., Girard, M., Ozakbas, S., Grammond, P., Zephir, H., Ciron, J., Maillart, E., Moreau, T., Amato, M. P., Labauge, P., Alroughani, R., Buzzard, K., Skibina, O., Terzi, M., Laplaud, D., Berger, E., Grand Maison, F., Lebrun-Frenay, C., Cartechini, E., Boz, C., Lechner-Scott, J., Clavelou, P., Stankoff, B., Prevost, J., Kappos, L., Pelletier, J., Shaygannejad, V., Yamout, B., Gerlach, O., Spitaleri, D., Pesch, V., Gout, O., Turkoglu, R., Heinzlef, O., Thouvenot, E., Vukusic, S., Butzkueven, H., and Kalincik, T.

40. 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.

41. The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

Author

Alexis Montcuquet, Henrik Kahr Mathiesen, Tomas Kalincik, Marc Girard, Karolina Hankiewicz, Marco Onofrj, Francois Grand Maison, Raed Alroughani, Mathilde Lefort, Olivier Gout, Jeannette Lechner-Scott, Marc Debouverie, Julie Prevost, Eva Havrdova, Olivier Casez, Per Soelberg Sørensen, Pierre Duquette, Jean Pelletier, Claudio Solaro, Alessandra Lugaresi, Francesco Patti, Emmanuelle Leray, Johanna Balslev Andersen, Bassem Yamout, Céline Labeyrie, Karen Schreiber, Eric Thouvenot, Nils Koch-Henriksen, Michael Broksgaard Jensen, Elisabeth Maillart, Chantal Nifle, Stephan Bramow, Pierre Clavelou, Bruno Stankoff, Olivier Heinzlef, Finn Sellebjerg, Abir Wahab, Mark Slee, Gilles Defer, Pierre Labauge, Melinda Magyari, Steve Vucic, Guillermo Izquierdo, Helmut Butzkueven, Peter Vestergaard Rasmussen, Bertrand Bourre, Maria Trojano, Franco Granella, Corinne Pottier, Jette L. Frederiksen, Olga Skibina, Recai Turkoglu, Ivania Patry, Pierre Grammond, Bart Van Wijmeersch, Eric Berger, Aurélie Ruet, Serkan Ozakbas, Jonathan Ciron, Tünde Csépány, Jean Philippe Camdessanche, Sandra Vukusic, Nicolas Maubeuge, David Laplaud, Cavit Boz, Christine Lebrun, Claudia C. Hilt Christensen, Patrizia Sola, Vahid Shaygannejad, Romain Casey, Murat Terzi, Philippe Cabre, Jérôme De Seze, Abdullatif Al-Khedr, Dana Horakova, Pamela A. McCombe, Daniele Spitaleri, Alexandre Prat, Gilles Edan, Hélène Zéphir, Aude Marousset, Sifat Sharmin, Diana Ferraro, Sara Eichau, Rana Karabudak, Thibault Moreau, Sellebjerg, Finn/0000-0002-1333-9623, Lugaresi, Alessandra/0000-0003-2902-5589, frederiksen, jette/0000-0003-1661-7438, Ciron, Jonathan/0000-0002-3386-6308, University of Copenhagen = Københavns Universitet (KU), University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Aarhus University Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The study was conducted separately and apart from the guidance of the sponsors. CORe received funding from NHMRC [1140766, 1129789, 1157717] to support studies of comparative effectiveness of MS therapies.OFSEP was 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, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation.DMSR did not receive any funding to collaborate in this study., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Andersen J.B., Sharmin S., Lefort M., Koch-Henriksen N., Sellebjerg F., Sorensen P.S., Hilt Christensen C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Eichau S., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Shaygannejad V., Prevost J., Skibina O., Solaro C., Karabudak R., Wijmeersch B.V., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., Seze J.D., Maillart E., Zephir H., Labauge P., Defer G., Lebrun C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Marousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Leray E., Laplaud D.A., Butzkueven H., Kalincik T., Vukusic S., Magyari M., University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Centre Hospitalier de Versailles André Mignot (CHV)

Subjects
medicine.medical_specialty, Fingolimod, Head-to-head comparison, Multiple sclerosis, Natalizumab, Treatment effectiveness, [SDV]Life Sciences [q-bio], Relapse rate, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Fingolimod Hydrochloride, Epidemiology, Humans, Medicine, Multiple sclerosi, Registries, 030212 general & internal medicine, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, First relapse, Treatment Outcome, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform meth-odologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/ exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab-and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed. BiogenBiogen; NovartisNovartis; MerckMerck & Company; RocheRoche Holding; Teva; Sanofi GenzymeSanofi-AventisGenzyme Corporation; NHMRCNational Health and Medical Research Council of Australia [1140766,1129789, 1157717]; French State; Agence Nationale de la Recherche-French National Research Agency (ANR)European Commission [ANR-10-COHO-002]; Eugene Devic EDMUS Foundation; ARSEP Foundation

Published
2021
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42. Determinants of therapeutic lag in multiple sclerosis

Author

Tomas Kalincik, Marc Girard, Corinne Pottier, Murat Terzi, Jean Pelletier, Oliver Gerlach, Julie Prevost, Dana Horakova, Francois Grand'Maison, Raed Alroughani, Guillermo Izquierdo, Francesco Patti, Federico Frascoli, Maria Trojano, Franco Granella, Pamela A. McCombe, Charles B Malpas, Recai Turkoglu, Aurélie Ruet, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Helmut Butzkueven, Pierre Clavelou, Tamara Castillo Trivino, Marco Onofrj, Jean Philippe Camdessanche, Pierre Labauge, Vincent Van Pesch, Pierre Grammond, Abir Wahab, Roberto Bergamaschi, Aysun Soysal, Diana Ferraro, Bertrand Bourre, Olivier Gout, Jeannette Lechner-Scott, Sara Eichau, Emmanuelle Leray, Alexis Montcuquet, Pierre Duquette, Olivier Casez, Youssef Sidhom, Patrizia Sola, Bart Van Wijmeersch, Izanne Roos, Gilles Edan, Serkan Ozakbas, David Laplaud, Sandra Vukusic, Abdullatif Al Khedr, Céline Labeyrie, Philippe Cabre, Eric Thouvenot, Céline Louapre, Romain Casey, Alessandra Lugaresi, Riadh Gouider, Alasdair Coles, Eric Berger, Ivania Patry, Gerardo Iuliano, Elisabetta Cartechini, Cavit Boz, Karolina Hankiewicz, Eva Havrdova, Eduardo Aguera-Morales, J William L Brown, Jérôme De Seze, Bruno Stankoff, Olivier Heinzlef, Gilles Defer, Alexandre Prat, Chantal Nifle, Maria José Sá, Marc Debouverie, Daniele Spitaleri, Aude Maurousset, Thibault Moreau, Christine Lebrun-Frenay, Hélène Zéphir, University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Charles University [Prague], Università degli studi di Catania [Catania], Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Università degli Studi di Modena e Reggio Emilia (UNIMORE), University of Queensland [Brisbane], Monash University [Clayton], UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charles University [Prague] (CU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Virgen Macarena, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), CHU Toulouse [Toulouse], INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, 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 [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), CHU Lille, Fernando Pessoa University, Azienda Ospedaleria Universitaria di Modena, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Karadeniz Technical University (KTU), Università degli Studi di Macerata = University of Macerata (UNIMC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Newcastle [Australia] (UoN), Zuyderland Hospital [Heerlen, The Netherlands], Ondokuz Mayis University, University of Parma = Università degli studi di Parma [Parme, Italie], Amiri hospital, University of Salerno (UNISA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hasselt University (UHasselt), San Giuseppe Moscati Hospital [Avellino, Italie], Bakirkoy Matern & Childrens State Hosp, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Universidad de Córdoba [Cordoba], Hospital Donostia, CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHI Poissy-Saint-Germain, Université de la Manouba [Tunisie] (UMA), University of Debrecen, Hôpital Charles Nicolle [Rouen], CHU Amiens-Picardie, CHU de la Martinique [Fort de France], CHU Limoges, CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], This study was supported by the EDMUS Foundation and NHMRC [1140766,1129189, 1157717]. IR is supported by a MSIF-ARSEP McDonald fellowship grantand a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profitorganization that receives support from Biogen, Novartis, Merck, Roche, Teva andSanofi Genzyme. The study was conducted separately and apart from the guidanceof the sponsors. The Observatoire Français de la Sclérose en Plaques (OFSEP) issupported by a grant provided by the French State and handled by the 'AgenceNationale de la Recherche,' within the framework of the 'Investments for the Future'program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUSFoundation against multiple sclerosis and by the ARSEP Foundation., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Roos I., Leray E., Frascoli F., Casey R., Brown J.W.L., Horakova D., Havrdova E.K., Debouverie M., Trojano M., Patti F., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grammond P., Ciron J., Ruet A., Ozakbas S., De Seze J., Louapre C., Zephir H., Sa M.J., Sola P., Ferraro D., Labauge P., Defer G., Bergamaschi R., Lebrun-Frenay C., Boz C., Cartechini E., Moreau T., Laplaud D., Lechner-Scott J., Grand'Maison F., Gerlach O., Terzi M., Granella F., Alroughani R., Iuliano G., Van Pesch V., Van Wijmeersch B., Spitaleri D.L.A., Soysal A., Berger E., Prevost J., Aguera-Morales E., McCombe P., Castillo Trivino T., Clavelou P., Pelletier J., Turkoglu R., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Sidhom Y., Gouider R., Csepany T., Bourre B., Al Khedr A., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Coles A., Malpas C.B., Vukusic S., Butzkueven H., Kalincik T., Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], 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), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), University of Newcastle [Callaghan, Australia] (UoN), Ondokuz Mayis University (OMU), Università degli studi di Parma = University of Parma (UNIPR), Universidad de Córdoba = University of Córdoba [Córdoba], University of Debrecen Egyetem [Debrecen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Registrie, Male, medicine.medical_specialty, Treatment response, Pediatrics, Neurology, Lag, [SDV]Life Sciences [q-bio], Aucun, multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Recurrence, medicine, Humans, Treatment effect, Disabled Persons, Registries, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Delayed onset, medicine.disease, 3. Good health, Clinical neurology, therapeutic lag, multiple sclerosi, Disease Progression, Disabled Person, Observational study, Female, observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract

International audience; Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS

Published
2021
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43. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

Author

Mark Slee, Guillermo Izquierdo, Per Soelberg Soerensen, Karen Schreiber, Alexandre Prat, Francois Grand'Maison, Maria Trojano, Franco Granella, Pierre Duquette, David Laplaud, Elisabeth Maillart, Henrik Kahr Mathiesen, Bassem Yamout, Cavit Boz, Jean Pelletier, Corinne Pottier, Jette L. Frederiksen, Claudia Christina Pfleger, Tomas Kalincik, Olivier Gout, Daniele Spitaleri, Marc Girard, Marco Onofrj, Jérôme De Seze, Helmut Butzkueven, Emmanuelle Leray, Philippe Cabre, Julie Prevost, Abullatif Al-Khedr, Aude Maurousset, Eric Berger, Sifat Sharmin, Ivania Patry, Pamela A. McCombe, Patrizia Sola, Olga Skibina, Diana Ferraro, Pierre Clavelou, Francesco Patti, Finn Sellebjerg, Niels Koch-Henriksen, Alexis Montcuquet, Recai Turkoglu, Romain Casey, Bart Van Wijmeersch, Hélène Zéphir, Pierre Grammond, Dana Horakova, Davide Maimone, Serkan Ozakbas, Céline Labeyrie, Murat Terzi, Aurélie Ruet, Steve Vucic, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Bruno Stankoff, Mathilde Lefort, Katherine Buzzard, Karolina Hankiewicz, Jean-Philippe Camdessanché, Raed Alroughani, Michael Broksgaard Jensen, Pierre Labauge, Olivier Casez, Peter Vestergaard Rasmussen, Bertrand Bourre, Olivier Heinzlef, Gilles Defer, Gilles Edan, Alessandra Lugaresi, Abir Wahab, Melinda Magyari, Anneke van der Walt, Eva Havrdova, Johanna Balslev Andersen, Chantal Nifle, Stephan Bramow, Marc Debouverie, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Jeannette Lechner-Scott, Eric Thouvenot, Sharmin S., Lefort M., Andersen J.B., Leray E., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand'Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Prevost J., Maimone D., Skibina O., Buzzard K., Van der Walt A., Van Wijmeersch B., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., De Seze J., Maillart E., Zephir H., Labauge P., Defer G., Lebrun-Frenay C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Laplaud D., Koch-Henriksen N., Sellebjerg F.T., Soerensen P.S., Pfleger C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Magyari M., Vukusic S., Butzkueven H., Kalincik T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), Charles University [Prague] (CU), Amiri hospital, Hospital Virgen Macarena, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), University of Catania [Italy], G.F. Ingrassia Hospital, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Neurological Science of Bologna (IRCCS), Ondokuz Mayis University (OMU), American University of Beirut Faculty of Medicine and Medical Center (AUB), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Karadeniz Technical University (KTU), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Queensland [Brisbane], Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Flinders University [Adelaide, Australia], University of Newcastle [Callaghan, Australia] (UoN), Azienda Ospedaleria Universitaria di Modena, Università degli studi di Parma = University of Parma (UNIPR), University Hospital Parma, Monash University [Melbourne], The Alfred Hospital, Hasselt University (UHasselt), University of Debrecen Egyetem [Debrecen], San Giuseppe Moscati Hospital [Avellino, Italie], Westmead Hospital [Sydney], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, Service de neurologie [Amiens], CHU Amiens-Picardie, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), 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), 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), Aarhus University Hospital, Aalborg University [Denmark] (AAU), University Hospital of Northern Sealand, Rigshospitalet [Copenhagen], Copenhagen University Hospital, The Royal Melbourne Hospital, 1140766, National Health and Medical Research Council, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Bologna, University of Bari Aldo Moro (UNIBA), University of Newcastle [Australia] (UoN), University of Parma = Università degli studi di Parma [Parme, Italie], University of Debrecen, Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Ondokuz Mayis University, Centre de recherche en neurosciences de Lyon (CRNL), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, 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), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Internationality, Subgroup analysis, Rate ratio, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, 030225 pediatrics, Internal medicine, Secondary Prevention, Medicine, Humans, Immunologic Factors, Pharmacology (medical), Longitudinal Studies, Registries, 10. No inequality, Expanded Disability Status Scale, business.industry, Proportional hazards model, Fingolimod Hydrochloride, Multiple sclerosis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, medicine.disease, Fingolimod, 3. Good health, multiple sclerosis, sex, age, natalizumab, fingolimod, big data, Psychiatry and Mental health, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed withweighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤38 years (0.64; 0.54–0.76); in those withdisease duration ≤7 years (0.63; 0.53–0.76); in those with EDSS score 38 years (1.34; 1.04–1.73); those with disease duration >7 years (1.33; 1.01–1.74); those with EDSS score

Published
2021
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44. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author

Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Bergamaschi, Roberto, Sá, Maria José, Cartechini, Elisabetta, Boz, Cavit, Granella, Franco, Hupperts, Raymond, Terzi, Murat, Lechner-Scott, Jeannette, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Olascoaga, Javier, Prevost, Julie, Aguera-Morales, Eduardo, Slee, Mark, Csepany, Tunde, Turkoglu, Recai, Sidhom, Youssef, Gouider, Riadh, Van Wijmeersch, Bart, McCombe, Pamela, Macdonell, Richard, Coles, Alasdair, Malpas, Charles, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, Duquette, Pierre, Grand'Maison, Francois, Iuliano, Gerardo, Ramo-Tello, Cristina, Solaro, Claudio, Cabrera-Gomez, Jose Antonio, Rio, Maria Edite, Bolaños, Ricardo Fernandez, Shaygannejad, Vahid, Oreja-Guevara, Celia, Sanchez-Menoyo, Jose Luis, Petersen, Thor, Altintas, Ayse, Barnett, Michael, Flechter, Shlomo, Fragoso, Yara, Amato, Maria Pia, Moore, Fraser, Ampapa, Radek, Verheul, Freek, Hodgkinson, Suzanne, Cristiano, Edgardo, Yamout, Bassem, Laureys, Guy, Dominguez, Jose Andres, Zwanikken, Cees, Deri, Norma, Dobos, Eniko, Vrech, Carlos, Butler, Ernest, Rozsa, Csilla, Petkovska-Boskova, Tatjana, Karabudak, Rana, Rajda, Cecilia, Alkhaboori, Jabir, Saladino, Maria Laura, Shaw, Cameron, Shuey, Neil, Vucic, Steve, Sempere, Angel Perez, Campbell, Jamie, Piroska, Imre, Taylor, Bruce, van der Walt, Anneke, Kappos, Ludwig, Roullet, Etienne, Gray, Orla, Simo, Magdolna, Sirbu, Carmen-Adella, Brochet, Bruno, Cotton, François, De Sèze, Jérôme, Dion, Armelle, Douek, Pascal, Guillemin, Francis, Laplaud, David, Lebrun-Frenay, Christine, Moreau, Thibault, Olaiz, Javier, Pelletier, Jean, Rigaud-Bully, Claire, Stankoff, Bruno, Marignier, Romain, Debouverie, Marc, Edan, Gilles, Ciron, Jonathan, Ruet, Aurélie, Collongues, Nicolas, Lubetzki, Catherine, Vermersch, Patrick, Labauge, Pierre, Defer, Gilles, Cohen, Mikaël, Fromont, Agnès, Wiertlewsky, Sandrine, Berger, Eric, Clavelou, Pierre, Audoin, Bertrand, Giannesini, Claire, Gout, Olivier, Thouvenot, Eric, Heinzlef, Olivier, Al-Khedr, Abdullatif, Bourre, Bertrand, Casez, Olivier, Cabre, Philippe, Montcuquet, Alexis, Créange, Alain, Camdessanché, Jean-Philippe, Faure, Justine, Maurousset, Aude, Patry, Ivania, Hankiewicz, Karolina, Pottier, Corinne, Maubeuge, Nicolas, Labeyrie, Céline, Nifle, Chantal, University of Melbourne, The Royal Melbourne Hospital, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, University of Cambridge [UK] (CAM), Medicine Charles University and General Faculty Hospital in Prague, University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Universitario Virgen Macarena [Seville, Spain], University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université de Montréal (UdeM), University of Modena and Reggio Emilia, Partenaires INRAE, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), IRCCS Mondino Foundation, Universidade Fernando Pessoa, KTU Medical Faculty Farabi Hospital, University of Parma = Università degli studi di Parma [Parme, Italie], Zuyderland Ziekenhuis, Medical Faculty [Samsun, Turkey], University of Newcastle [Australia] (UoN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Hospital Universitario Donostia, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Haydarpasa Numune Training and Research Hospital, Hasselt University (UHasselt), University of Queensland [Brisbane], Hitachi Cambridge Laboratory [University of Cambridge], Hitachi, Ltd-University of Cambridge [UK] (CAM), Monash University [Melbourne], Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Ospedali Riuniti di Salerno, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 1157717, National Health and Medical Research Council, Biogen, MSIF-ARSEP McDonald, Melbourne Research Scholarship, French State, ‘Agence Nationale de la Recherche,’, ANR-10-COHO-002, ‘Investments for the Future’, Eugène Devic EDMUS Foundation, ARSEP Foundation, Novartis, Merck, Roche, Teva Pharmaceutical Industries, Sanofi Genzyme, EDMUS Foundation, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Roos I., Leray E., Frascoli F., Casey R., Brown W.J.L., Horakova D., Havrdova E.K., Trojano M., Patti F., Izquierdo G., Eichau S., Onofrj M., Lugaresi A., Prat A., Girard M., Grammond P., Sola P., Ferraro D., Ozakbas S., Bergamaschi R., Sa M.J., Cartechini E., Boz C., Granella F., Hupperts R., Terzi M., Lechner-Scott J., Spitaleri D., van Pesch V., Soysal A., Olascoaga J., Prevost J., Aguera-Morales E., Slee M., Csepany T., Turkoglu R., Sidhom Y., Gouider R., van Wijmeersch B., McCombe P., Macdonell R., Coles A., Malpas C.B., Butzkueven H., Vukusic S., Kalincik T., Duquette P., Grand'Maison F., Iuliano G., Ramo-Tello C., Solaro C., Cabrera-Gomez J.A., Rio M.E., Bolanos R.F., Shaygannejad V., Oreja-Guevara C., Sanchez-Menoyo J.L., Petersen T., Altintas A., Barnett M., Flechter S., Fragoso Y., Amato M.P., Moore F., Ampapa R., Verheul F., Hodgkinson S., Cristiano E., Yamout B., Laureys G., Dominguez J.A., Zwanikken C., Deri N., Dobos E., Vrech C., Butler E., Rozsa C., Petkovska-Boskova T., Karabudak R., Rajda C., Alkhaboori J., Saladino M.L., Shaw C., Shuey N., Vucic S., Sempere A.P., Campbell J., Piroska I., Taylor B., van der Walt A., Kappos L., Roullet E., Gray O., Simo M., Sirbu C.-A., Brochet B., Cotton F., de Seze J., Dion A., Douek P., Guillemin F., Laplaud D., Lebrun-Frenay C., Moreau T., Olaiz J., Pelletier J., Rigaud-Bully C., Stankoff B., Marignier R., Debouverie M., Edan G., Ciron J., Ruet A., Collongues N., Lubetzki C., Vermersch P., Labauge P., Defer G., Cohen M., Fromont A., Wiertlewsky S., Berger E., Clavelou P., Audoin B., Giannesini C., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Creange A., Camdessanche J.-P., Faure J., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Apollo - University of Cambridge Repository, McCombe, Pamela/0000-0003-2704-8517, Slee, Mark/0000-0003-4323-2453, Brown, William/0000-0002-7737-5834, Laplaud, David/0000-0001-6113-6938, Ciron, Jonathan/0000-0002-3386-6308, Roos, Izanne/0000-0003-0371-3666, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Kalincik, Tomas, Girard, Marc, Patti, Francesco, Horakova, Dana, Malpas, Charles B., Olascoaga, Javier, Prevost, Julie, Roos, Izanne, Hupperts, Raymond, Csepany, Tunde, VAN WIJMEERSCH, Bart, Ferraro, Diana, Aguera-Morales, Eduardo, Cartechini, Elisabetta, Vukusic, Sandra, Frascoli, Federico, Lugaresi, Alessandra, Sa, Maria Jose, Butzkueven, Helmut, Spitaleri, Daniele, Macdonell, Richard, Coles, Alasdair, Havrdova, Eva K., Granella, Franco, Turkoglu, Recai, Trojano, Maria, Sola, Patrizia, Van Pesch, Vincent, Onofrj, Marco, Grammond, Pierre, Bergamaschi, Roberto, Izquierdo, Guillermo, McCombe, Pamela, Slee, Mark, Eichau, Sara, Prat, Alexandre, Leray, Emmanuelle, Soysal, Aysun, Terzi, Murat, Brown, J. William L., Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Ozakbas, Serkan, Casey, Romain, Lechner-Scott, Jeannette, Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Hospital Universitario Virgen Macarena [Séville], Università degli studi di Parma = University of Parma (UNIPR), University of Newcastle [Callaghan, Australia] (UoN), University of Cambridge [UK] (CAM)-Hitachi, Ltd, and ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010)

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, multiple sclerosis, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Randomized controlled trial, law, Internal medicine, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, therapeutic lag, business.industry, Multiple sclerosis, Interferon beta-1a, Middle Aged, medicine.disease, Fingolimod, 3. Good health, Treatment Outcome, Cohort, Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Immunotherapies, 030217 neurology & neurosurgery, Immunosuppressive Agents, Therapeutic lag, prognosis, treatment, medicine.drug, Cohort study, Follow-Up Studies
Abstract

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag. This study was supported by the EDMUS Foundation, Biogen and NHMRC (1140766, 1129189, 1157717). I.R. is supported by a MSIF-ARSEP McDonald fellowship grant and a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The Observatoire Francais de la Sclerose en Plaques (OFSEP) 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, by the Eugene Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. The study was conducted separately and apart from the guidance of the sponsors. Kalincik, T (corresponding author), Univ Melbourne, Dept Med, CORe, 300 Grattan St, Melbourne, Vic 3050, Australia. tomas.kalincik@unimelb.edu.au

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45. 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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46. Advocating for rituximab as first-line treatment for NMOSD-AQP4 patients in France: Cost and efficacy considerations.

Author

Deschamps R, Papeix C, Ayrignac X, Bourre B, Ciron J, Cohen M, Collongues N, Deiva K, Durand Dubief F, Laplaud DA, Maillart E, Michel L, Pique J, Ruet A, Thouvenot E, Zéphir H, Marignier R, and Audoin B

Subjects
Humans, France epidemiology, Immunologic Factors economics, Immunologic Factors therapeutic use, Treatment Outcome, Rituximab therapeutic use, Rituximab economics, Neuromyelitis Optica drug therapy, Neuromyelitis Optica economics, Aquaporin 4 immunology, Cost-Benefit Analysis
Published
2024
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47. Neurosarcoidosis: Clinical, biological, and MRI presentation of central nervous system disease in a national multicenter cohort.

Author

Dos Santos A, Courtin E, Ruet A, Duffau P, Mathey G, Bekkour I, Ciron J, Michel L, Blanc FX, Aguilar J, Lejeune P, Marc G, Laplaud D, Magot A, Hamidou M, and Wiertlewski S

Subjects
Humans, Male, Female, Middle Aged, Adult, Retrospective Studies, France, Aged, Immunosuppressive Agents therapeutic use, Adrenal Cortex Hormones therapeutic use, Sarcoidosis diagnostic imaging, Sarcoidosis drug therapy, Central Nervous System Diseases diagnostic imaging, Central Nervous System Diseases drug therapy, Magnetic Resonance Imaging
Abstract

Introduction: Neurosarcoidosis (NS) is a systemic inflammatory granulomatous disease affecting of patients with sarcoidosis. Its diagnosis is difficult as there is no specific test for it. Because of its rarity, the management of NS has so far only been described in case series and short retrospective cohorts. The objective of this study is description of the clinical, paraclinical presentation and the therapeutic management of central nervous system (CNS) involvement in NS patients in France., Methods: This multicenter, retrospective, observational study involved patients hospitalized between 2010 and 2019 with a diagnosis of sarcoidosis and CNS involvement., Results: We included 118 patients (38 with isolated NS, 80 with NS associated with systemic sarcoidosis). NS was the initial presentation in 78% of patients, with cranial nerve involvement (36%), medullary symptoms (23%), and seizures (21%). Twenty-one percent of the patients had already been diagnosed with systemic sarcoidosis. The most frequent biological abnormality was lymphopenia (62.5%), while angiotensin-converting enzyme was increased in 21%. Meningitis was present in 45% and hyperproteinorachia in 69.5% of cases. MRI mainly revealed white matter abnormalities and leptomeningeal enhancement (34%). Corticosteroids were the most useful treatment, and immunosuppressive agents were used in steroid-resistant patients and to limit side effects. Methotrexate, cyclophosphamide, and anti-TNFα were also used, exhibiting good efficacy., Conclusions: This cohort contributes to a better understanding of the clinical phenotype and associated imaging and biological abnormalities. Sharing of clinical, biological, and imaging data, as well as the therapeutic responses, of patients with NS helps to better understand and manage this disease that affects a small number of patients per center. A database project could be implemented in the future to enable this., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Published
2024
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49. Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

Author

Deschamps R, Guillaume J, Ciron J, Audoin B, Ruet A, Maillart E, Pique J, Benyahya L, Laplaud DA, Michel L, Collongues N, Cohen M, Ayrignac X, Thouvenot E, Zephir H, Bourre B, Froment Tilikete C, Moreau T, Cantagrel P, Kerschen P, Cabasson S, Maubeuge N, Hankiewicz K, Nifle C, Berger E, Megherbi H, Magy L, Klapczynski F, Sarov Riviere M, Giannesini C, Hamelin L, Giroux M, Branger P, Maurousset A, Mathey G, Moulin M, Mélé N, Papeix C, and Marignier R

Subjects
Humans, Male, Female, Adult, Middle Aged, Aged, Young Adult, Autoantibodies blood, France epidemiology, Cohort Studies, Follow-Up Studies, Optic Neuritis, Recurrence, Myelin-Oligodendrocyte Glycoprotein immunology
Abstract

Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Published
2024
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50. 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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