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115 results on '"Vukusic S"'

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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2. 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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3. Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Author: Spelman, T, Magyari, M, Butzkueven, H, Van Der Walt, A, Vukusic, S, Trojano, M, Iaffaldano, P, Horáková, D, Drahota, J, Pellegrini, F, Hyde, R, Duquette, P, Lechner-Scott, J, Sajedi, SA, Lalive, P, Shaygannejad, V, Ozakbas, S, Eichau, S, Alroughani, R, Terzi, M, Girard, M, Kalincik, T, Grand'Maison, F, Skibina, O, Khoury, SJ, Yamout, B, Sa, MJ, Gerlach, O, Blanco, Y, Karabudak, R, Oreja-Guevara, C, Altintas, A, Hughes, S, McCombe, P, Ampapa, R, de Gans, K, McGuigan, C, Soysal, A, Prevost, J, John, N, Inshasi, J, Stawiarz, L, Manouchehrinia, A, Forsberg, L, Sellebjerg, F, Glaser, A, Pontieri, L, Joensen, H, Rasmussen, PV, Sejbaek, T, Poulsen, MB, Christensen, JR, Kant, M, Stilund, M, Mathiesen, H, Hillert, J, Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP, Spelman, T, Magyari, M, Butzkueven, H, Van Der Walt, A, Vukusic, S, Trojano, M, Iaffaldano, P, Horáková, D, Drahota, J, Pellegrini, F, Hyde, R, Duquette, P, Lechner-Scott, J, Sajedi, SA, Lalive, P, Shaygannejad, V, Ozakbas, S, Eichau, S, Alroughani, R, Terzi, M, Girard, M, Kalincik, T, Grand'Maison, F, Skibina, O, Khoury, SJ, Yamout, B, Sa, MJ, Gerlach, O, Blanco, Y, Karabudak, R, Oreja-Guevara, C, Altintas, A, Hughes, S, McCombe, P, Ampapa, R, de Gans, K, McGuigan, C, Soysal, A, Prevost, J, John, N, Inshasi, J, Stawiarz, L, Manouchehrinia, A, Forsberg, L, Sellebjerg, F, Glaser, A, Pontieri, L, Joensen, H, Rasmussen, PV, Sejbaek, T, Poulsen, MB, Christensen, JR, Kant, M, Stilund, M, Mathiesen, H, Hillert, J, and Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP
Abstract: BACKGROUND: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. OBJECTIVE: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. METHODS: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. RESULTS: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1
Published: 2023

4. 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

5. 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

6. 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

7. 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

8. 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

9. Myelin-oligodendrocyte glycoprotein antibody-associated disease

Author: Marignier, R. Hacohen, Y. Cobo-Calvo, A. Pröbstel, A.-K. Aktas, O. Alexopoulos, H. Amato, M.-P. Asgari, N. Banwell, B. Bennett, J. Brilot, F. Capobianco, M. Chitnis, T. Ciccarelli, O. Deiva, K. De Sèze, J. Fujihara, K. Jacob, A. Kim, H.J. Kleiter, I. Lassmann, H. Leite, M.-I. Linington, C. Meinl, E. Palace, J. Paul, F. Petzold, A. Pittock, S. Reindl, M. Sato, D.K. Selmaj, K. Siva, A. Stankoff, B. Tintore, M. Traboulsee, A. Waters, P. Waubant, E. Weinshenker, B. Derfuss, T. Vukusic, S. Hemmer, B.
Abstract: Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD. © 2021 Elsevier Ltd
Published: 2021

10. 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

11. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author: Patsopoulos, NA, Baranzini, SE, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, AH, James, T, Replogle, J, Vlachos, IS, McCabe, C, Pers, TH, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, IP, Robbins, A, Andlauer, TFM, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, HB, Sellebjerg, F, Sorensen, PS, Ullum, H, Thorner, LW, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, CM, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, MD, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, MA, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, SD, Celius, EG, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, IL, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, SJ, Calabresi, P, Cree, BAC, Cross, A, Davis, M, de Bakker, PWI, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, IY, Gourraud, PA, Haines, JL, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, MH, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, CP, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, MA, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, RJ, Lechner-Scott, J, Leal, R, Moscato, P, Booth, DR, Stewart, GJ, Vucic, S, Pame, G, BamettO, M, Mason, D, GriffithS, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, BV, Charlesworth, J, Kilpatrick, TJ, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, WM, Kermode, AG, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, JF, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, JP, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, GW, Ng, SME, Oikonomnou, J, Peeters, H, Proctor, DD, Rahier, JF, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, DA, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, HF, Hauser, SL, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, LF, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, McCauley, JL, Oksenberg, JR, Oturai, A, Sawcer, S, Ivinson, AJ, Olsson, T, De Jager, PL, Patsopoulos, Na, Baranzini, Se, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, Ah, James, T, Replogle, J, Vlachos, I, Mccabe, C, Pers, Th, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, Ip, Robbins, A, Andlauer, Tfm, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, Hb, Sellebjerg, F, Sorensen, P, Ullum, H, Thorner, Lw, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, Cm, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, Md, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, Ma, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, Sd, Celius, Eg, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, Il, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, Sj, Calabresi, P, Cree, Bac, Cross, A, Davis, M, de Bakker, Pwi, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, Iy, Gourraud, Pa, Haines, Jl, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, Mh, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, Cp, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, Ma, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, Rj, Lechner-Scott, J, Leal, R, Moscato, P, Booth, Dr, Stewart, Gj, Vucic, S, Pame, G, Bametto, M, Mason, D, Griffiths, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, Bv, Charlesworth, J, Kilpatrick, Tj, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, Wm, Kermode, Ag, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, Jf, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, Gw, Ng, Sme, Oikonomnou, J, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, Km, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H, Mathew, Cg, Palmer, Cna, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cca, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, Da, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, Hf, Hauser, Sl, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, Lf, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, Mccauley, Jl, Oksenberg, Jr, Oturai, A, Sawcer, S, Ivinson, Aj, Olsson, T, De Jager, Pl, Neurology, and Immunology
Subjects: 0301 basic medicine, Multiple Sclerosis, Quantitative Trait Loci, Inheritance Patterns, Cell Cycle Proteins, Genome-wide association study, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Major Histocompatibility Complex, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Gene Frequency, Autoimmune Process, medicine, Humans, RNA-Seq, X chromosome, Genetics, Chromosomes, Human, X, Multidisciplinary, Microglia, Multiple sclerosis, GTPase-Activating Proteins, Chromosome Mapping, Genomics, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Genetic Loci, Case-Control Studies, biology.protein, Genome-Wide Association Study, 030217 neurology & neurosurgery
Abstract: Genetic roots of multiple sclerosis The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis. Science , this issue p. eaav7188 ; see also p. 1383
Published: 2019

12. Aggressive multiple sclerosis (2): Treatment

Author: Arrambide, G., Iacobaeus, E., Amato, M. P., Derfuss, T., Vukusic, S., Hemmer, B., Brundin, L., Tintore, M., Berger, J., Boyko, A., Brinar, V., Brownlee, W., Ciccarelli, O., Coles, A., Correale, J., Cutter, G., Edan, G., Evangelou, N., Fernandez, O., Frederiksen, J., Gold, R., Hacohen, Y., Hartung, H. -P., Hellwig, K., Hillert, J., Imitola, J., Kalincik, T., Kappos, L., Khoury, S., Kim, H. J., Havrdova, E. K., Liblau, R., Lycke, J., Montalban, X., Muraro, P., Reingold, S., Schmierer, K., Sellebjerg, F., Sorensen, P. S., Solari, A., Sormani, M. P., Thompson, A., Trapp, B., Tremlett, H., Trojano, M., Tur, C., Uccelli, A., van Pesch, V., and Waubant, E.
Subjects: Aggressive, medicine.medical_specialty, Treatment response, relapsing–remitting, Disease, Permanent disability, multiple sclerosis, disability, highly active, treatment response, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, 2018 ECTRIMS Focused Workshop Group, medicine, Relapsing-remitting, 030212 general & internal medicine, Intensive care medicine, Highly active, Therapeutic window, Neurology & Neurosurgery, Disability, business.industry, 1103 Clinical Sciences, medicine.disease, ddc, Natural history, Neurology, Relapsing remitting, Neurology (clinical), business, 1109 Neurosciences, 030217 neurology & neurosurgery, Meeting Reviews
Abstract: Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The workshop on which the manuscript is based was supported in its entirety by the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS). The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.
Published: 2020

13. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis

Author: Louapre, C. (Céline), Collongues, N. (Nicolas), Stankoff, B. (Bruno), Giannesini, C. (Claire), Papeix, C. (Caroline), Bensa, C. (Caroline), Deschamps, R. (Romain), Créange, A. (Alain), Wahab, A. (Abir), Pelletier, J. (Jean), Heinzlef, O. (Olivier), Labauge, P. (Pierre), Guilloton, L. (Laurent), Ahle, G. (Guido), Goudot, M. (Mathilde), Bigaut, K. (Kevin), Laplaud, D. (David-Axel), Vukusic, S. (Sandra), Lubetzki, C. (Catherine), and De Sèze, J. (Jérôme)
Subjects: Aucun
Abstract: Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P
Published: 2020

14. Aggressive multiple sclerosis (1) : Towards a definition of the phenotype

Author: Iacobaeus, E., Arrambide, G., Amato, M. P., Derfuss, T., Vukusic, S., Hemmer, B., Tintore, M., Brundin, L., Berger, J., Boyko, A., Brinar, V., Brownlee, W., Ciccarelli, O., Coles, A., Correale, J., Cutter, G., Edan, G., Evangelou, N., Fernandez, O., Frederiksen, J., Gold, R., Hacohen, Y., Hartung, H. -P., Hellwig, K., Hillert, J., Imitola, J., Kalincik, T., Kappos, L., Khoury, S., Kim, H. J., Havrdova, E. K., Liblau, R., Lycke, J., Montalban, X., Muraro, P., Reingold, S., Schmierer, K., Sellebjerg, F., Sorensen, P. S., Solari, A., Sormani, M. P., Thompson, A., Trapp, B., Tremlett, H., Trojano, M., Tur, C., Uccelli, A., van Pesch, V., Waubant, E., UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie
Subjects: Disease subtype, Aggressive, medicine.medical_specialty, Severe disease, Aggressive disease, multiple sclerosis, Relapsing/remitting, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, disability, highly active, observational studies, relapsing/remitting, 2018 ECTRIMS Focused Workshop Group, medicine, Intensive care medicine, Secondary progressive, Highly active, Observational studies, 030304 developmental biology, 0303 health sciences, Neurology & Neurosurgery, Disability, business.industry, 1103 Clinical Sciences, medicine.disease, Phenotype, Additional research, ddc, Neurology, Observational study, Neurology (clinical), 1109 Neurosciences, business, 030217 neurology & neurosurgery, Meeting Reviews
Abstract: Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The workshop on which the manuscript is based was supported in its entirety by the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS). While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.
Published: 2020

15. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author: Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, 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, Sá, MJ, 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, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, Douek, P, Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, 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, Sá, MJ, 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, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, and Douek, P
Published: 2020

16. Aggressive multiple sclerosis (2): Treatment.

Author: Arrambide, G, Iacobaeus, E, Amato, MP, Derfuss, T, Vukusic, S, Hemmer, B, Brundin, L, Tintore, M, 2018 ECTRIMS Focused Workshop Group, Arrambide, G, Iacobaeus, E, Amato, MP, Derfuss, T, Vukusic, S, Hemmer, B, Brundin, L, Tintore, M, and 2018 ECTRIMS Focused Workshop Group
Abstract: The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.
Published: 2020

17. Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

Author: Iacobaeus, E, Arrambide, G, Amato, MP, Derfuss, T, Vukusic, S, Hemmer, B, Tintore, M, Brundin, L, 2018 ECTRIMS Focused Workshop Group, Iacobaeus, E, Arrambide, G, Amato, MP, Derfuss, T, Vukusic, S, Hemmer, B, Tintore, M, Brundin, L, and 2018 ECTRIMS Focused Workshop Group
Abstract: While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.
Published: 2020

18. 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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19. Multiple sclerosis registries in Europe – An updated mapping survey

Author: Glaser, A., Stahmann, A., Meissner, T., Flachenecker, P., Horáková, D., Zaratin, P., Brichetto, G., Pugliatti, M., Rienhoff, O., Vukusic, S., de Giacomoni, A. C., Battaglia, M. A., Brola, W., Butzkueven, H., Casey, R., Drulovic, J., Eichstädt, K., Hellwig, K., Iaffaldano, P., Ioannidou, E., Kuhle, J., Lycke, K., Magyari, M., Malbaša, T., Middleton, R., Myhr, K. M., Notas, K., Orologas, A., Otero-Romero, S., Pekmezovic, T., Sastre-Garriga, J., Seeldrayers, P., Soilu-Hänninen, M., Stawiarz, L., Trojano, M., Ziemssen, T., Hillert, J., Thalheim, C., Glaser, A., Stahmann, A., Meissner, T., Flachenecker, P., Horáková, D., Zaratin, P., Brichetto, G., Pugliatti, M., Rienhoff, O., Vukusic, S., de Giacomoni, A. C., Battaglia, M. A., Brola, W., Butzkueven, H., Casey, R., Drulovic, J., Eichstädt, K., Hellwig, K., Iaffaldano, P., Ioannidou, E., Kuhle, J., Lycke, K., Magyari, M., Malbaša, T., Middleton, R., Myhr, K. M., Notas, K., Orologas, A., Otero-Romero, S., Pekmezovic, T., Sastre-Garriga, J., Seeldrayers, P., Soilu-Hänninen, M., Stawiarz, L., Trojano, M., Ziemssen, T., Hillert, J., and Thalheim, C.
Published: 2019

20. Gender Inequities in the Multiple Sclerosis Community: A Call for Action

Author: Waubant, E, Amezcua, L, Sicotte, N, Hellwig, K, Krupp, L, Weinstock-Guttman, B, Yeh, A, Lucas, RM, Longbrake, EE, Yadav, V, Rensel, M, Mar, S, Hersh, C, Block, V, Zipp, F, Han, MH, Spain, R, Kelland, EE, Charvet, L, Dimitri, D, Papeix, C, Cross, AH, Inglese, M, Amato, MP, Airas, L, Leray, E, Sormani, MP, Van der Walt, A, Vukusic, S, Castillo-Trivino, T, Tenembaum, S, Ciccarelli, O, Bommarito, G, Petracca, M, Celius, EG, Carson, MJ, Hua, LH, Van der Mei, I, Lubetzki, C, Jokubaitis, V, Trojano, M, Voskuhl, R, Tintore, M, Harbo, H, Asgari, N, Piccio, L, Burton, JM, Tremlett, H, Goldman, MD, Michel, L, Zhang, Y, Bove, R, Quandt, JA, Costello, F, Ionete, C, Lebrun-Frenay, C, Pakpoor, J, Bevan, C, Morrow, SA, Waldman, AT, Oh, J, Jacobs, D, Palace, J, Marrie, RA, Tiwari-Woodruff, SK, Metz, LM, Cortese, R, Chitnis, T, Benson, L, Benveniste, ET, Conway, J, Sand, IK, Murphy, JO, Kita, M, Riley, C, Goverman, JM, Langer-Gould, AM, Azevedo, CJ, Morales, IB, Barcellos, LF, Crabtree, E, Plummer, P, Shirani, A, Whartenby, K, Brilot-Turville, F, Kingwell, E, Coyle, P, Mowry, E, Zabad, R, Bielekova, B, Monson, N, Laule, C, Burnett, M, Schreiner, T, Grinspan, J, Dobson, R, Akassoglou, K, Graves, J, Gray, O, Smyth, P, Havrdova, EK, Preiningerova, JL, Banwell, B, Makhani, N, Lucchinetti, C, Arrambide, G, Maillart, E, Macklin, W, Gilmore, W, Waubant, E, Amezcua, L, Sicotte, N, Hellwig, K, Krupp, L, Weinstock-Guttman, B, Yeh, A, Lucas, RM, Longbrake, EE, Yadav, V, Rensel, M, Mar, S, Hersh, C, Block, V, Zipp, F, Han, MH, Spain, R, Kelland, EE, Charvet, L, Dimitri, D, Papeix, C, Cross, AH, Inglese, M, Amato, MP, Airas, L, Leray, E, Sormani, MP, Van der Walt, A, Vukusic, S, Castillo-Trivino, T, Tenembaum, S, Ciccarelli, O, Bommarito, G, Petracca, M, Celius, EG, Carson, MJ, Hua, LH, Van der Mei, I, Lubetzki, C, Jokubaitis, V, Trojano, M, Voskuhl, R, Tintore, M, Harbo, H, Asgari, N, Piccio, L, Burton, JM, Tremlett, H, Goldman, MD, Michel, L, Zhang, Y, Bove, R, Quandt, JA, Costello, F, Ionete, C, Lebrun-Frenay, C, Pakpoor, J, Bevan, C, Morrow, SA, Waldman, AT, Oh, J, Jacobs, D, Palace, J, Marrie, RA, Tiwari-Woodruff, SK, Metz, LM, Cortese, R, Chitnis, T, Benson, L, Benveniste, ET, Conway, J, Sand, IK, Murphy, JO, Kita, M, Riley, C, Goverman, JM, Langer-Gould, AM, Azevedo, CJ, Morales, IB, Barcellos, LF, Crabtree, E, Plummer, P, Shirani, A, Whartenby, K, Brilot-Turville, F, Kingwell, E, Coyle, P, Mowry, E, Zabad, R, Bielekova, B, Monson, N, Laule, C, Burnett, M, Schreiner, T, Grinspan, J, Dobson, R, Akassoglou, K, Graves, J, Gray, O, Smyth, P, Havrdova, EK, Preiningerova, JL, Banwell, B, Makhani, N, Lucchinetti, C, Arrambide, G, Maillart, E, Macklin, W, and Gilmore, W
Published: 2018

21. Fampridine-PR (prolonged released 4-aminopyridine) improves upper limb dysfunction in multiple sclerosis patients: Clinical and kinematic analysis

Author: Cheiney-Kulak, C., primary, Revol, P., additional, Durand-Dubief, F., additional, Ionescu, I., additional, Roggerone, S., additional, Benoit, A., additional, Delporte, L., additional, Roche, L., additional, Rabilloud, M., additional, Vukusic, S., additional, Rossetti, Y., additional, and Jacquin-Courtois, S., additional
Published: 2018
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22. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study

Author: Barbin, L. (Laetitia), Rousseau, C. (Chloe), Jousset, N. (Natacha), Casey, R. (Romain), Debouverie, M. (Marc), Vukusic, S. (Sandra), De Seze, J. (Jerome), Brassat, D. (David), Wiertlewski, S. (Sandrine), Brochet, B. (Bruno), Pelletier, J. (Jean), Vermersch, P. (Patrick), Edan, G. (Gilles), Lebrun-Frenay, C. (Christine), Clavelou, P. (Pierre), Thouvenot, E. (Eric), Camdessanché, J. (Jean-Philippe), Tourbah, A. (Ayman), Stankoff, B. (Bruno), Al Khedr, A. (Abdullatif), Cabre, P. (Philippe), Papeix, C. (Caroline), Berger, E. (Eric), Heinzlef, O. (Olivier), Debroucker, T. (Thomas), Moreau, T. (Thibault), Gout, O. (Olivier), Bourre, B. (Bertrand), Créange, A. (Alain), Labauge, P. (Pierre), Magy, L. (Laurent), Defer, G. (Gilles), Foucher, Y. (Yohann), Laplaud, D. (David A), CFSEP and OFSEP groups, Jonchère, Laurent, 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), Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), ReLSEP, Lorraine Register of MS, EA 4360, Department of Neurology, CHU Nancy, Department of Neurology, CHU Lyon, Service de Neurologie [Lyon], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Bordeaux (UB), Pôle de Neurosciences Cliniques, Department of Neurology, Hôpital de la Timone [CHU - APHM] (TIMONE), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de neurologie D, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Clermont-Ferrand, CHU Saint-Etienne, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurologie [CHRU Besançon], Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondation Ophtalmologique Rothschild, Excitabilité nerveuse et thérapeutique (ENT), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), CHU Limoges, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), 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 Régional Universitaire de Nancy (CHRU Nancy), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université de Rennes 1 (UR1), 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 des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), and Service de Neurologie [CHU Besançon]
Subjects: Male, [SDV]Life Sciences [q-bio], Aucun, diagnosis, drug therapy, epidemiology, Cohort Studies, 0302 clinical medicine, Natalizumab, Medicine, 030212 general & internal medicine, 10. No inequality, Fingolimod, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Cohort, Female, France, Immunosuppressive Agents, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Multiple Sclerosis, Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC], Article, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Fingolimod Hydrochloride, Internal medicine, Humans, Immunologic Factors, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Surgery, Propylene Glycols, therapeutic use, Propensity score matching, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: OBJECTIVE: To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French follow-up cohort Observatoire of Multiple Sclerosis. METHODS: Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0-5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting). RESULTS: The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation. CONCLUSION: Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod. comparative study journal article multicenter study observational study research support, non-u.s. gov't 2016 Feb 23 2016 01 29 imported
Published: 2016

23. Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid

Author: Marignier, R., primary, Ruiz, A., additional, Cavagna, S., additional, Nicole, A., additional, Watrin, C., additional, Touret, M., additional, Parrot, S., additional, Malleret, G., additional, Peyron, C., additional, Benetollo, C., additional, Auvergnon, N., additional, Vukusic, S., additional, and Giraudon, P., additional
Published: 2016
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24. Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial

Author: Edan, G, Comi, G, Le Page, E, Leray, E, Rocca, Ma, Filippi, M, French–Italian Mitoxantrone Interferon beta 1b Trial Group Trojano, M, Paolicelli, D, D'Onghia, M, Rumbach, L, Clavelou, P, Aufauvre, D, Moreau, T, Amato, Mp, Portaccio, E, Ghezzi, A, Mancardi, A, Vermersch, P, Hautecoeur, P, De Sèze, J, Magy, L, Vallat, Jm, Confavreux, C, Vukusic, S, Ionescu, I, Blanc, S, Pelletier, J, Malikova Klemina, I, Ranjeva, Jp, Debouverie, M, Pittion, S, Lebrun, C, Roullet, E, Heinzlef, O, Gout, O, Lubetzki, C, Stankoff, B, Tourbah, A, Veillard, D, Warter, Jm, Tranchant, C, Berry, I, Brassat, D, Clanet, M, Durelli, Luca, Clerico, Marinella, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), École des Hautes Études en Santé Publique [EHESP] (EHESP), Edan, G, Comi, Giancarlo, Le Page, E, Leray, E, Rocca, Ma, Filippi, Massimo, French Italian Mitoxantrone Interferon beta 1b Trial, Group, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)
Subjects: Oncology, Male, medicine.medical_treatment, Gadolinium, Severity of Illness Index, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, 030212 general & internal medicine, 10. No inequality, Brain, Immunosuppression, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Methylprednisolone, Drug Therapy, Combination, Female, Immunosuppressive Agents, medicine.drug, Interferon beta-1b, Adult, medicine.medical_specialty, Multiple Sclerosis, Neuroimaging, Drug Administration Schedule, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Immunologic Factors, Mitoxantrone, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Interferon-beta, medicine.disease, Surgery, Secondary progressive, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Objectives: The long-term impact of interferon-beta-1b (IFN) might be improved by short-term immunosuppression with mitoxantrone (MITOX) in aggressive relapsing-remitting multiple sclerosis (ARMS) patients. Methods: In this 3-year clinical and MRI study, 109 ARMS patients (two or more relapses in the previous 12 months and one or more gadolinium (Gd)-enhancing MRI lesion) were randomised into two groups: 54 patients received MITOX monthly (12 mg/m2; maximum 20 mg) combined with 1 g of methylprednisolone (MP) for 6 months followed by IFN for the last 27 months, and 55 patients received IFN for 3 years combined with 1 g of MP monthly for the first 6 months. The primary endpoint was the time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months. Results: The time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months was delayed by 18 months in the MITOX group compared with the IFN group (p
Published: 2011

25. Treating systematic errors in multiple sclerosis data

Author: Heigenhauser, L., Confavreux, C., Daumer, Martin, Ebers, G. C., Kappos, L., Lederer, C., Neiß, A., Polman, C., and Vukusic, S.
Subjects: ddc:519
Abstract: Multiple sclerosis (MS) is characterized by high variability between patients and, more importantly here, within an individual over time. This makes categorization and prognosis difficult. Moreover, it is unclear to what degree this intra-individual variation reflects the long-term course of irreversible disability and what is attributable to short-term processes such as relapses, to interrater variability and to measurement error. Any investigation and prediction of the medium or long term evolution of irreversible disability in individual patients is therefore confronted with the problem of systematic error in addition to random fluctuations. The approach described in this article aims to assist in detecting relapses in disease curves and in identifying the underlying disease course. To this end neurological knowledge was transformed into simple rules which were then implemented into computer algorithms for pre-editing disease curves. Based on simulations it is shown that pre-editing time series of disability measured with the Expanded Disability Status Scale (EDSS) can lead to more robust and less biased estimates for important disease characteristics, such as baseline EDSS and time to reach certain EDSS levels or sustained progression.
Published: 2005

26. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse

Author: Vukusic, S., Hutchinson, M., Hours, M., Moreau, Thibault, Cortinovis-Tourniaire, P., Adeleine, P., Confavreux, C., Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Published: 2004

27. Reliability of Longitudinal Brain Volume Loss Measurements between 2 Sites in Patients with Multiple Sclerosis: Comparison of 7 Quantification Techniques

Author: Durand-Dubief, F., primary, Belaroussi, B., additional, Armspach, J.P., additional, Dufour, M., additional, Roggerone, S., additional, Vukusic, S., additional, Hannoun, S., additional, Sappey-Marinier, D., additional, Confavreux, C., additional, and Cotton, F., additional
Published: 2012
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28. Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility

Author: Couturier, N., primary, Bucciarelli, F., additional, Nurtdinov, R. N., additional, Debouverie, M., additional, Lebrun-Frenay, C., additional, Defer, G., additional, Moreau, T., additional, Confavreux, C., additional, Vukusic, S., additional, Cournu-Rebeix, I., additional, Goertsches, R. H., additional, Zettl, U. K., additional, Comabella, M., additional, Montalban, X., additional, Rieckmann, P., additional, Weber, F., additional, Muller-Myhsok, B., additional, Edan, G., additional, Fontaine, B., additional, Mars, L. T., additional, Saoudi, A., additional, Oksenberg, J. R., additional, Clanet, M., additional, Liblau, R. S., additional, and Brassat, D., additional
Published: 2011
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29. Unusual mechanism of monocular oscillopsia

Author: Jasse, L., primary, Vighetto, A., additional, Vukusic, S., additional, Pelisson, D., additional, Pisella, L., additional, and Tilikete, C., additional
Published: 2010
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30. Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases

Author: Labauge, P., primary, Horzinski, L., additional, Ayrignac, X., additional, Blanc, P., additional, Vukusic, S., additional, Rodriguez, D., additional, Mauguiere, F., additional, Peter, L., additional, Goizet, C., additional, Bouhour, F., additional, Denier, C., additional, Confavreux, C., additional, Obadia, M., additional, Blanc, F., additional, Seze, J. d., additional, Fogli, A., additional, and Boespflug-Tanguy, O., additional
Published: 2009
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31. Regional variations in the prevalence of multiple sclerosis in French farmers

Author: Vukusic, S., primary, Van Bockstael, V., additional, Gosselin, S., additional, and Confavreux, C., additional
Published: 2006
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32. Reply to: Age at disability milestones in multiple sclerosis and history of multiple sclerosis: a unifying concept

Author: Confavreux, C., primary and Vukusic, S., additional
Published: 2006
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33. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process.

Author: Confavreux C, Vukusic S, Adeleine P, Confavreux, Christian, Vukusic, Sandra, and Adeleine, Patrice
Published: 2003

34. Regional variations in the prevalence of multiple sclerosis in French farmers.

Author: Vukusic S, Van Bockstael V, Gosselin S, Confavreux C, Vukusic, Sandra, Van Bockstael, Vincent, Gosselin, Sophie, and Confavreux, Christian
Abstract: Background: Studies on the prevalence of multiple sclerosis have been carried out worldwide, showing a heterogeneous distribution between countries and even between the different regions of the same country.Methods: We estimated the regional and national prevalence of multiple sclerosis in France on 1 January 2003, based on the computerised database of the national farmer health insurance system ("Mutualité Sociale Agricole").Results: There were 2667 cases of multiple sclerosis registered on the prevalence date, out of 4,098,477 affiliates. After standardisation on age, estimates for the national prevalence of multiple sclerosis in French farmers were 65.0 per 100,000 inhabitants (95% confidence interval 62.5 to 67.5), 41.9 per 100,000 in men (39.1 to 44.7) and 96.3 per 100,000 in women (92.0 to 100.6). The prevalence of multiple sclerosis was significantly higher in the north eastern regions (approximately 100 per 100,000 inhabitants) compared with the south western regions (around 50 per 100,000 inhabitants).Conclusion: Our study is the first to evaluate the overall prevalence of multiple sclerosis in France and its 22 regions using the same methodology. Our results may be generalised to the whole French population as there is no convincing evidence of an increased or decreased susceptibility to multiple sclerosis among farmers or persons living in the countryside. This places France among the countries of medium to high prevalence. Confirming the uneven distribution of multiple sclerosis that correlates with latitude, raises once more the question of the role of genetic and environmental factors in the susceptibility to multiple sclerosis. [ABSTRACT FROM AUTHOR]
Published: 2007

35. Outcome of patients with sarcoidosis refractory to TNF antagonists: A case series

Author: Thery-Casari, C., Yvan Jamilloux, Bouvry, D., Chapelon-Abric, C., Marquet, A., Bielefeld, P., Schleinitz, N., Vukusic, S., Girszyn, N., Fain, O., Bonnet, F., Valeyre, D., Seve, P., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MORPH3Eus, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Background: Tumor necrosis factor (TNF) antagonists have been reported as an efficient third-line therapy for sarcoidosis but there is no data regarding patients who do not respond to this treatment. Objective: To report the characteristics, the outcome and the response to therapy of patients with sarcoidosis resistant to TNF antagonists. Methods: Patients from the French STAT (Sarcoidosis Treatment with Anti-TNF) registry who were classified as non-responders and who were followed-up for >1 year were included. The response to further therapies was classified as complete response, or partial response, and the others were classified as non-responders. Results: Among the 132 patients from the registry, 14 were considered as non-responders to anti-TNF. Nine patients (66% of women; mean age 48 years) were analyzed. The mean number of organs involved was 4.2. Seven patients were previously treated with more than 2 immunosuppressive treatments. The mean duration of the anti-TNF treatment was 9 months (range, 3-24). After a mean follow-up duration of 58 months (median, 35; range, 19-128) a complete response was observed in 2/9 cases, a partial response in 5/9 cases, and 2/9 cases were considered as non-responders. In all but one patient, the immunosuppressant that allowed the clinical response had previously been used. Furthermore, the dosage was not necessarily increased to gain efficacy. Non-responders were treated by corticosteroids only because of their comorbidities or noncompliance. Conclusion: In patients who do not respond to TNF antagonists, previously used immunosuppressants may be useful. Excluding a differential diagnosis, assessing compliance and testing for anti-drug antibodies should be systematic.

36. 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

37. 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

38. 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

39. Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis.

Author: Androdias G, Noroy L, Psimaras D, Birzu C, Pelletier J, Beigneux Y, Branger P, Ciron J, Dananchet Y, Depaz R, Froment Tilikete C, Gignoux L, Grosset-Janin C, Joubert B, Kerschen P, Kwiatkowski A, Lebrun-Frenay C, Maillart E, Maureille A, Nicolas P, Roux T, Marignier R, and Vukusic S
Subjects: Humans, Middle Aged, Immune Checkpoint Inhibitors adverse effects, Retrospective Studies, Prospective Studies, Recurrence, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy
Abstract: Objectives: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation., Methods: This French multicentric study collected retrospective and prospective data on patients with MS treated with ICIs after a cancer diagnosis., Results: We identified 18 patients with a median age of 48 years. Three of them (17%), all aged 50 years or younger, with a relapsing-remitting course, showed clinical and/or radiologic signs of MS activity 3 to 6 months after ICI initiation. They had stopped disease-modifying treatment (DMT) several months earlier, at the time of cancer diagnosis. Only one had both clinical and MRI activity, with mild severity and complete recovery., Discussion: Our study suggests that the overall risk of MS activity under ICI is low and could be mainly driven by DMT discontinuation, as in MS in general. Although larger studies are needed for better risk assessment in younger patients with more active disease, ICI should be considered when needed in patients with MS.
Published: 2024
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40. Priority setting: women's health topics in multiple sclerosis.

Author: Ross L, Finlayson M, Amato MP, Cohen JA, Hellwig K, Tintore M, Vukusic S, Salter A, and Marrie RA
Abstract: Background: A scoping review found that most studies on women's health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies addressed menopause, contraception, gynecologic cancers/cancer screening. However, the perceived relative importance of these knowledge gaps to people living with MS and other partners is unknown. We engaged a range of partners, including people living with MS, health care providers, researchers, and patient advocacy groups, to set priorities for future research in women's health in MS., Methods: We employed a three-step global engagement process. First, we identified which broad research topics relevant to women's health in MS were of highest priority using two surveys. Second, we developed specific research questions within these topics using focus groups. Finally, we prioritized the research questions with a third survey., Results: Overall, 5,266 individuals responded to the initial surveys [ n = 1,430 global survey, mean (SD) age 50.0 (12.6), all continents; n = 3,836 North American Research Committee on Multiple Sclerosis survey, mean (SD) age 64.8 (9.6), United States]. Menopause, sexual dysfunction, pregnancy, gynecologic cancer/cancer screening, hormones and parenthood were identified as the most important topics. Focus groups generated 80 potential research questions related to these topics. In the final survey 712 individuals prioritized these questions. The highest priority questions in each research topic were: (i) How do perimenopause and menopause affect disease activity, course, response to disease-modifying treatment and quality of life in MS; (ii) What are the most effective strategies for managing issues around sexual intimacy, including related to low sexual desire, changes in physical function, and MS symptoms; (iii) Are there long-term effects of disease-modifying therapies on the children of persons with MS; (iv) What are the short and long-term effects of disease-modifying drugs on gynecologic cancer risk, particularly for high efficacy disease-modifying drugs and hematopoietic stem cell transplantation; (v) Are there hormone related treatments that can stabilize fluctuations in MS symptoms; and (vi) How does MS fatigue impact parenting strategies., Conclusion: Priorities for research relating to women's health issues for persons with MS have been delineated using a collaborative process with key partners. Alignment of future research with these priorities should be monitored., Competing Interests: RM receives research funding from: CIHR, Research Manitoba, MS Canada, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. LR received research funding from the National Multiple Sclerosis Society. SV has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Janssen, Merck, Novartis, Roche, Sandoz and Sanofi. JC has received personal compensation for consulting for Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an Editor of Multiple Sclerosis Journal. MF holds research funding from MS Canada, and has received consulting or teaching honoraria from Novartis and Biogen. KH received personal compensation as a speaker for Biogen, Bristol-Myers Squibb, Roche, Teva, Novartis, Bayer, Sanofi-Genzyme and Merck. She receives currently funding by the Innovations fonds, the National MS society, Biogen, Teva, Novartis, Roche, Sanofi-Genzyme and Merck. MT has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma, Relapse Adjudication Committee for IMCYSE SA. MA has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Janssen, Merck, Novartis, Roche, Sandoz, Sanofi and Celgene BMS. AS receives research funding from Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, Consortium of MS Centers and the US Department of Defense and is a member of editorial board for Neurology. She serves as a consultant for Gryphon Bio, LLC and Abata Therapeutics. She is a member of the Data and Safety Monitoring Board for Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2), Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), and Methotrexate treatment of Arthritis caused by Chikungunya virus (MARCH). The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ross, Finlayson, Amato, Cohen, Hellwig, Tintore, Vukusic, Salter and Marrie.)
Published: 2024
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41. Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Author: Spelman T, Magyari M, Butzkueven H, Van Der Walt A, Vukusic S, Trojano M, Iaffaldano P, Horáková D, Drahota J, Pellegrini F, Hyde R, Duquette P, Lechner-Scott J, Sajedi SA, Lalive P, Shaygannejad V, Ozakbas S, Eichau S, Alroughani R, Terzi M, Girard M, Kalincik T, Grand'Maison F, Skibina O, Khoury SJ, Yamout B, Sa MJ, Gerlach O, Blanco Y, Karabudak R, Oreja-Guevara C, Altintas A, Hughes S, McCombe P, Ampapa R, de Gans K, McGuigan C, Soysal A, Prevost J, John N, Inshasi J, Stawiarz L, Manouchehrinia A, Forsberg L, Sellebjerg F, Glaser A, Pontieri L, Joensen H, Rasmussen PV, Sejbaek T, Poulsen MB, Christensen JR, Kant M, Stilund M, Mathiesen H, and Hillert J
Abstract: Background: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods., Objective: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry., Methods: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect., Results: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006)., Conclusion: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices., Competing Interests: TSp received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen; and speaker honoraria from Novartis. MM has served on the scientific advisory board for Sanofi, Novartis, and Merck and has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. HB is an employee of Monash University and has accepted travel compensation from Merck; his institution receives honoraria for talks, steering committee activities, and research grants from Roche, Merck, Biogen, Novartis, UCB Pharma, Medical Research Future Fund Australia, NHMRC Australia, Trish MS Foundation, MS Australia, and the Pennycook Foundation. He receives personal compensation for steering group activities for the Brain Health Initiative from the Oxford Health Policy Forum and is funded by an NHMRC Australia Investigator Grant. SV received consulting and lecturing fees, travel grants, and research support from Biogen, Celgene, Genentech, Genzyme, Medday Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi Aventis, and Teva Pharma. MT has served on scientific advisory boards for Biogen, Novartis, Roche, and Genzyme; has received speaker honoraria and travel support from Biogen Idec, Sanofi Aventis, Merck Serono, Teva, Genzyme, and Novartis; and has received research grants for her institution from Biogen Idec, Merck Serono, and Novartis. PI has served on scientific advisory boards for Biogen Idec, Bayer, Teva, Roche, Merck Serono, Novartis, and Genzyme and has received funding for travel and/or speaker honoraria from Sanofi Aventis, Genzyme, Biogen Idec, Teva, Merck Serono, and Novartis. DH was supported by the Charles University Cooperation Program in Neuroscience, the project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) funded by the European Union (Next Generation EU), and by the General University Hospital in Prague project MH CZ-DRO-VFN64165. She also received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen Idec. FP is an employee of Biogen. RH is an employee of Biogen and holds stock. PD served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme. JL-S received travel compensation from Novartis, Biogen, Roche, and Merck. Her institution receives honoraria for talks and advisory board commitments, as well as research grants from Biogen, Merck, Roche, TEVA, and Novartis. SS declared no competing interests. PL received honoraria for speaking and/or travel expenses from Biogen, Merck, Novartis, Roche; consulting fees from Biogen, GeNeuro, Merck, Novartis, Roche; and research support from Biogen, Merck, Novartis. None were related to this work. SE received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva. RAI received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche, and Sanofi-Genzyme. MT received travel grants from Novartis, Bayer-Schering, Merck, and Teva; and has participated in clinical trials by Sanofi Aventis, Roche, and Novartis. MG received consulting fees from Teva Canada Innovation, Biogen, Novartis, and Genzyme Sanofi; and lecture payments from Teva Canada Innovation, Novartis, and EMD. He has also received a research grant from the Canadian Institutes of Health Research. TK served on scientific advisory boards for MS International Federation and World Health Organization, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck, and Biogen; on the steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL, and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck. FG received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, and ATARA Pharmaceuticals. OS received honoraria and consulting fees from Bayer-Schering, Novartis, Merck, Biogen, and Genzyme. SK received compensation for scientific advisory board activity from Merck and Roche. BY received honoraria as a speaker and member of scientific advisory boards from Sanofi, Bayer, Biogen, Merck, Janssen, Novartis, Roche, and Aspen. MJ received consulting fees, speaker honoraria, and/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck Serono, Novartis, Roche, Sanofi, and Teva. YB received speaker honoraria/consulting fees from Merck, Biogen, Roche, Bristol Myers Squibb, Novartis, Sanofi, and Sandoz. CO-G received honoraria as a consultant on scientific advisory boards from Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, and TEVA. AA received speaker honoraria from Novartis and Alexion. SH has received unrestricted educational grants or speaking honoraria from Biogen, Merck Serono, Novartis, Roche, and Sanofi Genzyme. PM received speaker fees and travel grants from Novartis, Biogen, T'évalua, and Sanofi. RAm received conference travel support from Novartis, Teva, Biogen, Bayer, and Merck and has participated in clinical trials by Biogen, Novartis, Teva, and Actelion. KdG served on scientific advisory boards for Roche, Janssen, Sanofi-Genzyme, Novartis, and Merck, received conference fees and travel support from Novartis, Biogen, Sanofi-Genzyme, Teva, AbbVie, and Merck, and received educational event support from Novartis. CM received honoraria as a consultant on scientific advisory boards for Genzyme, BMS, Janssen, Biogen, Merck, Roche, and Novartis; has received travel grants from Roche and Novartis. JP accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme, and Teva. NJ is a local principal investigator on commercial studies funded by Novartis, Biogen, Amicus, and Sanofi. JI declared no competing interests. FS has served on scientific advisory boards for, served as a consultant for, received support for congress participation, or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. HJ declared no competing interests. PR has served on scientific advisory boards for, served as consultant for, received support for congress participation, or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi Genzyme. TSe received and has served on scientific advisory boards for, served as a consultant for, received support for congress participation, or received speaker honoraria from Biogen, Merck, Novartis, Roche, and Sanofi. T. Sejbaeks received unrestricted research grants to his research institution from Biogen, Merck, and Roche and is currently engaged in sponsor-initiated research projects by Eisai, Lundbeck, Roche, and Sanofi. MP declared no competing interests. JC has received speaker honoraria from Biogen. MS has served on scientific advisory boards for, served as a consultant for, received support for congress participation, participated in industrial trials with, or received speaker honoraria from Bayer, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. JH has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme, and Novartis and speaker's fees from Biogen, Novartis, Merck Serono, Bayer-Schering, Teva, and Sanofi-Genzyme. He has served as P.I. for projects or received unrestricted research support from BiogenIdec, Merck Serono, TEVA, Sanofi-Genzyme, and Bayer-Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain Foundation. The authors declare that this study received funding from Biogen. The funder had the following involvement with the study: study design and manuscript review. The funder was not involved in the collection of data, analysis, writing of the article, or the decision to submit it for publication. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Spelman, Magyari, Butzkueven, Van Der Walt, Vukusic, Trojano, Iaffaldano, Horáková, Drahota, Pellegrini, Hyde, Duquette, Lechner-Scott, Sajedi, Lalive, Shaygannejad, Ozakbas, Eichau, Alroughani, Terzi, Girard, Kalincik, Grand'Maison, Skibina, Khoury, Yamout, Sa, Gerlach, Blanco, Karabudak, Oreja-Guevara, Altintas, Hughes, McCombe, Ampapa, de Gans, McGuigan, Soysal, Prevost, John, Inshasi, Stawiarz, Manouchehrinia, Forsberg, Sellebjerg, Glaser, Pontieri, Joensen, Rasmussen, Sejbaek, Poulsen, Christensen, Kant, Stilund, Mathiesen, Hillert and the Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP.)
Published: 2023
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42. Vaccine response in people with multiple sclerosis treated with fumarates.

Author: Tremblay MA, Vukusic S, Shanmugasundaram M, Bozin I, Levin S, Gocke A, and Wipfler P
Abstract: People with multiple sclerosis (pwMS) have an increased risk of infection. As disease-modifying therapies (DMTs) and other treatments may interact with the immune system, there may be concerns about vaccine efficacy and safety. Therefore, it is important to evaluate possible interactions between DMTs and vaccines. The fumarates, dimethyl fumarate, diroximel fumarate, and monomethyl fumarate, are approved for the treatment of relapsing multiple sclerosis. This review assesses the evidence on vaccine response in pwMS treated with fumarates, with a particular focus on COVID-19 vaccines. Treatment with fumarates does not appear to result in blunting of humoral responses to vaccination; for COVID-19 vaccines, particularly RNA-based vaccines, evidence indicates antibody responses similar to those of healthy recipients. While data on the effect of fumarates on T-cell responses are limited, they do not indicate any significant blunting. COVID-19 vaccines impart a similar degree of protection against severe COVID-19 infection for pwMS on fumarates as in the general population. Adverse reactions following vaccination are generally consistent with those observed in the wider population; no additional safety signals have emerged in those on fumarates. Additionally, no increase in relapse has been observed in pwMS following vaccination. In pwMS receiving fumarates, vaccination is generally safe and elicits protective immune responses., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MAT received research funding support from Biogen; consulting fees for medical advisory boards from Alexion, Biogen, Genentech, and TG Therapeutics; and speaker fees from Genentech. SV received lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, and Teva. MS and AG employees of and held stock/stock options in Biogen at the time of this work. IB and SL are employees of and hold stock/stock options in Biogen. PW received funding for travel and honoraria (for lectures and advisory boards) from Biogen, Celgene/BMS, Janssen-Cilag, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, and Teva., (© The Author(s), 2023.)
Published: 2023
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43. Association Between Anti-CD20 Therapies and COVID-19 Severity Among Patients With Relapsing-Remitting and Progressive Multiple Sclerosis.

Author: Januel E, Hajage D, Labauge P, Maillart E, De Sèze J, Zephir H, Pelletier J, Guilloton L, Bensa C, Heinzlef O, Casez O, Biotti D, Bourre B, Vukusic S, Maurousset A, Berger E, Laplaud D, Lebrun-Frénay C, Dubessy AL, Branger P, Thouvenot E, Clavelou P, Sellal F, Manchon E, Moreau T, Papeix C, Tubach F, and Louapre C
Subjects: Humans, Female, Adult, Middle Aged, Male, Cohort Studies, Retrospective Studies, COVID-19 Vaccines, Multiple Sclerosis, COVID-19
Abstract: Importance: In patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS clinical course., Objective: To assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS)., Design, Setting, and Participants: This multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death., Exposures: Current anti-CD20 therapy (ocrelizumab or rituximab)., Main Outcomes and Measures: The main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score-weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age., Results: A total of 1400 patients, 971 with RRMS (median age, 39.14 years [IQR, 31.38-46.80 years]; 737 [76.1%] female) and 429 with PMS (median age, 54.21 years [IQR, 48.42-60.14 years]; 250 [58.3%] female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio [OR], 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS., Conclusions and Relevance: In this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.
Published: 2023
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44. Immune Profiling Reveals the T-Cell Effect of Ocrelizumab in Early Relapsing-Remitting Multiple Sclerosis.

Author: Garcia A, Dugast E, Shah S, Morille J, Lebrun-Frenay C, Thouvenot E, De Sèze J, Le Page E, Vukusic S, Maurousset A, Berger E, Casez O, Labauge P, Ruet A, Raposo C, Bakdache F, Buffels R, Le Frère F, Nicot A, Wiertlewski S, Gourraud PA, Berthelot L, and Laplaud D
Subjects: Humans, Leukocytes, Mononuclear, Antibodies, Monoclonal, Humanized therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis drug therapy
Abstract: Background and Objectives: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in patients with relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular immune profiles and their association with disease activity at treatment start and under therapy, which may provide new clues on the mechanisms of action of OCR and on the disease pathophysiology., Methods: A first group of 42 patients with an early RR-MS, never exposed to disease-modifying therapy, was included in 11 centers participating to an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR. The phenotypic immune profile was comprehensively assessed by multiparametric spectral flow cytometry at baseline and after 24 and 48 weeks of OCR treatment on cryopreserved peripheral blood mononuclear cells and analyzed in relation to disease clinical activity. A second group of 13 untreated patients with RR-MS was included for comparative analysis of peripheral blood and CSF. The transcriptomic profile was assessed by single-cell qPCRs of 96 genes of immunologic interest., Results: Using an unbiased analysis, we found that OCR as an effect on 4 clusters of CD4 + T cells: one corresponding to naive CD4 + T cells was increased, the other clusters corresponded to effector memory (EM) CD4 + CCR6 - T cells expressing homing and migration markers, 2 of them also expressing CCR5 and were decreased by the treatment. Of interest, one CD8 + T-cell cluster was decreased by OCR corresponding to EM CCR5-expressing T cells with high expression of the brain homing markers CD49d and CD11a and correlated with the time elapsed since the last relapse. These EM CD8 + CCR5 + T cells were enriched in the CSF of patients with RR-MS and corresponded to activated and cytotoxic cells., Discussion: Our study provides novel insights into the mode of action of anti-CD20, pointing toward the role of EM T cells, particularly a subset of CD8 T cells expressing CCR5., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2023
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45. Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers.

Author: Forsberg L, Spelman T, Klyve P, Manouchehrinia A, Ramanujam R, Mouresan E, Drahota J, Horakova D, Joensen H, Pontieri L, Magyari M, Ellenberger D, Stahmann A, Rodgers J, Witts J, Middleton R, Nicholas R, Bezlyak V, Adlard N, Hach T, Lines C, Vukusic S, Soilu-Hänninen M, van der Walt A, Butzkueven H, Iaffaldano P, Trojano M, Glaser A, and Hillert J
Abstract: Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported., Materials and Methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published., Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned., Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Lars Forsberg has nothing to disclose. Tim Spelman has received compensation for serving on the scientific advisory board for Biogen and speaker honoraria from Novartis. Pernilla Klyve has nothing to disclose. Ali Manouchehrinia is supported by the Margaretha af Ugglas Foundation. Ryan Ramanujam has nothing to disclose. Elena Mouresan has nothing to disclose. Jiri Drahota has nothing to disclose. Dana Horakova was supported by the Czech Ministry of Education (project Cooperatio LF1, research area Neuroscience). She also received compensation for travel, speaker honoraria, and consultant fees from Biogen Idec, Novartis, Merck, Sanofi, Roche, and Teva, as well as support for research activities from Biogen Idec. Hanna Joensen has received honoraria for an advisory board from Biogen. Luigi Pontieri has nothing to disclose. Melinda Magyari has served on the scientific advisory board, served as a consultant for, received support for congress participation, and received speaker honoraria from Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, and Alexion. The Danish MR Registry received research support from Biogen, Genzyme, Roche, Merck, and Novartis. David Ellenberger has nothing to disclose. Alexander Stahmann has no personal pecuniary interests to disclose, other than being the lead of the German MS Registry, which receives funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German MS Trust, German MS Society, Biogen, Celgene (Bristol-Myers Squibb), Merck, Novartis, Roche, and Sanofi. None resulted in a conflict of interest. Jeff Rodgers has nothing to disclose. The UK MS Register is funded by the MS Society. James Witts has nothing to disclose. The UK MS Register is funded by the MS Society. Rod Middleton has nothing to disclose. The UK MS Register is funded by the MS Society. Richard Nicholas has received support from advisory boards from Roche and Biogen. He has grant support from the UK MS Society and Berkeley Foundation and is a vice chair of a NICE HTA committee. Vladimir Bezlyak is an employee of Novartis Pharma AG. Nicholas Adlard is an employee of Novartis Pharma AG. Thomas Hach is an employee of Novartis Pharma AG. Carol Lines is an employee of Novartis Pharma AG. Sandra Vukusic has received grants, personal fees, unrestricted research grants, and nonfinancial support from Biogen, BMS-Celgene, Genzyme, Janssen, Merck Serono, Novartis, Roche, Sanofi, and Teva. Merja Soilu-Hanninen has received congress fee covering and lecture and consultation fees by Biogen, Celgene, Merck, Novartis, Roche, Sanofi, and Teva. Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck, Alexion, NervGen, and Roche. She has received speaker's honoraria and travel support from Novartis, Roche, Biogen, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. Helmut Butzkueven's institution (Monash University) has received compensation for his services on scientific advisory boards and as a speaker from Biogen, Novartis, Roche, Merck, and UCB. He serves on steering committees for trials conducted by Biogen, Merck, and Novartis, and his institution has received research support from Roche, Merck, Novartis, and Biogen. Pietro Iaffaldano has received advisory board membership, speaker honoraria, and travel support from Almirall, Bayer Shering, Biogen, Genzyme, Merck, Novartis, Sanofi, Roche, Teva, and their local affiliates. Maria Trojano received advisory board membership, speaker honoraria, travel support and research grant from Almirall, Bayer Shering, Biogen, Genzyme, Merck, Novartis, Sanofi, Roche, Teva, and their local affiliates. Anna Glaser has received research support from Novartis. Jan Hillert has received honoraria for serving on advisory boards for Biogen, Celgene, Sanofi-Genzyme, Merck KGaA, Novartis, and Sandoz and speaker's fees from Biogen, Novartis, Merck KGaA, Teva, and Sanofi-Genzyme. He has served as PI for projects or received unrestricted research support from Biogen, Celgene, Merck KGaA, Novartis, Roche, and Sanofi-Genzyme. His MS research was funded by the Swedish Research Council and the Swedish Brain foundation., (© The Author(s), 2023.)
Published: 2023
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46. Effects of socioeconomic status on excess mortality in patients with multiple sclerosis in France: A retrospective observational cohort study.

Author: Wilson S, Calocer F, Rollot F, Fauvernier M, Remontet L, Tron L, Vukusic S, Le Page E, Debouverie M, Ciron J, Ruet A, De Sèze J, Zephir H, Moreau T, Lebrun-Frénay C, Laplaud DA, Clavelou P, Labauge P, Berger E, Pelletier J, Heinzlef O, Thouvenot E, Camdessanché JP, Leray E, Dejardin O, and Defer G
Abstract: Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status., Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality., Findings: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = -6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%-22.9%]) for men and 12.3% (95%CI [7.6%-17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients., Interpretation: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality., Funding: This study was funded by the ARSEP foundation "Fondation pour l'aide à la recherche sur la Sclérose en Plaques" (Grant Reference Number 1122). Data collection has been 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" programme, under the reference ANR-10-COHO-002, Observatoire Français de la Sclérose en Plaques (OFSEP)., Competing Interests: Sarah Wilson, Fabien Rollot, Mathieu Fauvernier, Laurent Remontet, Laure Tron, Marc Debouverie, Jérôme de Sèze, Thibault Moreau, Christine Lebrun Frenay, Pierre Labauge, Jean Pelletier and Olivier Dejardin report no disclosures. Floriane Calocer: received funding for the present research from the ARSEP foundation for a Postdoctoral Fellowship (payment to the institution), from the “Réseau Bas-Normand pour la SEP” for a Postdoctoral Fellowship (payment to the institution), from the Regional Council of Normandy (payment to the institution), from the Ecole Doctorale of Caen University for a training in LSHTD to conduct this research (payment to the institution). She received support for attending meetings and/or travel from the ARSEP Foundation (paid directly to herself, unrelated to this work). Sandra Vukusic: received grants or contracts (paid to her university hospital) from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva; received consulting fees from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva (paid to her university hospital); received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva (paid to her university hospital); received support for attending meetings and/or travel from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, participated on a Data Safety Monitoring Board or Advisory Board for Biogen (contracts with her university hospital), all of the above unrelated to this work. Emmanuelle Le Page: received payment or honoraria for consulting or lectures from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis Alexion; received research support from Teva and Biogen, and received academic research grants from PHRC and LFSEP, and a travel grant from the ARSEP Foundation; received payment for consulting from Biogen, Merck, Sanofi-Genzyme, and Novartis; received invitations for national and international congresses from Biogen, Merck, Sanofi-Genzyme, Novartis Alexion, all of the above unrelated to this work. Jonathan Ciron: participated on a Data Safety Monitory Board of Advisory Board with Biogen, Novartis, Merck, Sanofi, Roche, Alexion and BMS-Celgene (all unrelated to this work). Aurélie Ruet: Consultancy fees from Roche and Biogen, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck, Roche, Biogen, research grants (paid to the institution) from Roche, Biogen and Sanofi-Genzyme, and support for attending meetings and/or travel from Biogen, Novartis and Alexion, all of the above unrelated to this work. Hélène Zephir: received research support for one PhD student from Roche, and research support for one MD student from FHU Imminent, consulting fees from Biogen IDEC (Symposium Biogen Idec in ISNI congress); received payment or honoraria for lectures from Merck, received payment or honoraria for lectures and boards from Novartis, all of the above unrelated to this work. David-Axel Laplaud: received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Merck, Alexion, BMS, Roche and Novartis, all of the above unrelated to this work. Pierre Clavelou: received consulting fees from Biogen, Janssen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme and Teva Pharma; and support for attending meetings and/or travel from Sanofi-Genzyme, and participated on a Data Safety Monitoring Board or Advisory Board for Medday, Merck and Novartis. All of the above unrelated to this work. Eric Berger: received consulting fees from Novartis, Sanofi Aventis, Biogen, Genzyme, Roche and Teva Pharma; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Sanofi Aventis, Biogen, Genyme, Roche and Teva Pharma (all of the above unrelated to this work). Olivier Heinzlef: consulting fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall and BiogenIdec, support for attending meetings and/or travel grants from Novartis, Teva, Genzyme, Merck Serono and Biogen Idec and other financial or non-financial interests from Novartis, Teva, Genzyme, Merck Serono and BiogenIdec (all of the above unrelated to this work). Eric Thouvenot: received grants or contracts from Novartis and Biogen (paid to the institution), consulting fees from Merck, Novartis, Biogen and Celgene (paid directly to himself); received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck, Novartis, Biogen, Celgene (paid directly to himself). All of the above unrelated to this work. Jean Philippe Camdessanché: received grants or contracts from CSL-Behring, Grifols, Laboratoire Français des Biotechnologies, consulting fees from Akcea, Alexion, Alnylam, Argenx, Bristol Myers Squibb, Laboratoire Français des Biotechnologies, Pfizer, UCB Pharma, SNF-Floeger, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck-Serono, Natus, Novartis, Pfizer, UCB Pharma and Teva. Received support for attending meetings and/or travel from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck-Serono, Natus, Novartis, Pfizer, Teva, SNF-Floeger, all of the above unrelated to this work. Emmanuelle Leray: received consulting fees from Alexion, Merck, Novartis, Roche and Biogen, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi Genzyme, and received support for attending meetings and/or travel from Sanofi Genzyme, all of the above unrelated to this work. Gilles Defer Received research grants (paid to institution) from Biogen, Merck Serono, Novartis, Sanofi Genzyme; payment for speaker honoraria from Biogen, Merck Serono, Novartis, Sanofi Genzyme, Teva Pharmaceuticals, BMS; funding for travel from Biogen, Merck Serono, Novartis, Sanofi Genzyme, Teva Pharmaceuticals; and personal compensation for scientific advisory boards from Biogen, Merck Serono, Novartis, Sanofi Genzyme, Teva Pharmaceuticals, and BMS. All of the above unrelated to this work., (© 2022 The Author(s).)
Published: 2022
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47. Overall and patient-level comparative effectiveness of dimethyl fumarate and fingolimod: A precision medicine application to the Observatoire Français de la Sclérose en Plaques registry.

Author: Simoneau G, Jiang X, Rollot F, Tian L, Copetti M, Guéry M, Ruiz M, Vukusic S, de Moor C, and Pellegrini F
Abstract: Background: Comparing real-world effectiveness and tolerability of therapies for relapsing-remitting multiple sclerosis is increasingly important, though average treatment effects fail to capture possible treatment effect heterogeneity. With the clinical course of the disease being highly heterogeneous across patients, precision medicine methods enable treatment response heterogeneity investigations., Objective: To compare real-world effectiveness and discontinuation profiles between dimethyl fumarate and fingolimod while investigating treatment effect heterogeneity with precision medicine methods., Methods: Adults initiating dimethyl fumarate or fingolimod as a second-line therapy were selected from a French registry. The primary outcome was annualized relapse rate at 12 months. Seven secondary outcomes relative to discontinuation and disease progression were considered. A precision medicine framework was used to characterize treatment effect heterogeneity., Results: Annualized relapse rates at 12 months were similar for dimethyl fumarate and fingolimod. The odd of treatment persistence was 47% lower for patients treated with dimethyl fumarate relative to those treated with fingolimod (odds ratio: 0.53, 95% confidence interval: 0.39, 0.70). None of the five precision medicine scoring approaches identified treatment heterogeneity., Conclusion: These findings substantiated the similar effectiveness and different discontinuation profiles for dimethyl fumarate and fingolimod as a second-line therapy for relapsing-remitting multiple sclerosis, with no significant effect heterogeneity observed., Competing Interests: Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FP, MR, CM, GS, XJ, and CdM are employees of Biogen and hold stocks of the company. LT and MC received consulting fees from Biogen. The funder participated in the study conception and design, interpretation of findings, and drafting of the manuscript. FP had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. SV and FR have nothing to disclose., (© The Author(s), 2022.)
Published: 2022
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48. Treatment regimens for neuromyelitis optica spectrum disorder attacks: a retrospective cohort study.

Author: Demuth S, Guillaume M, Bourre B, Ciron J, Zephir H, Sirejacob Y, Kerbrat A, Lebrun-Frenay C, Papeix C, Michel L, Laplaud D, Vukusic S, Maillart E, Cohen M, Audoin B, Marignier R, and Collongues N
Subjects: Aquaporin 4, Autoantibodies, Cohort Studies, Humans, Retrospective Studies, Multiple Sclerosis, Neuromyelitis Optica drug therapy
Abstract: Background: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy., Methods: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome., Results: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response., Conclusions: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids., (© 2022. The Author(s).)
Published: 2022
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49. Comparative Effectiveness of Natalizumab Versus Anti-CD20 in Highly Active Relapsing-Remitting Multiple Sclerosis After Fingolimod Withdrawal.

Author: Rollot F, Couturier J, Casey R, Wiertlewski S, Debouverie M, Pelletier J, De Sèze J, Labauge P, Ruet A, Thouvenot E, Ciron J, Berger E, Gout O, Clavelou P, Stankoff B, Casez O, Bourre B, Zephir H, Moreau T, Lebrun-Frenay C, Maillart E, Edan G, Neau JP, Montcuquet A, Cabre P, Camdessanché JP, Defer G, Nasr HB, Maurousset A, Hankiewicz K, Pottier C, Leray E, Vukusic S, and Laplaud DA
Subjects: Antigens, CD20, Fingolimod Hydrochloride therapeutic use, Humans, Immunologic Factors adverse effects, Immunosuppressive Agents therapeutic use, Natalizumab adverse effects, Recurrence, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract: In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing-remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions., (© 2022. The American Society for Experimental NeuroTherapeutics, Inc.)
Published: 2022
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50. Women's Health in Multiple Sclerosis: A Scoping Review.

Author: Ross L, Ng HS, O'Mahony J, Amato MP, Cohen JA, Harnegie MP, Hellwig K, Tintore M, Vukusic S, and Marrie RA
Abstract: Background: Women with multiple sclerosis (MS) may face challenges related to managing reproduction, pregnancy, and menopause while simultaneously managing their disease. The purpose of this scoping review was to map the literature broadly related to topics relevant to women's health in MS to inform the clinical and research communities about the existing types and sources of evidence and knowledge gaps. Apart from coverage of topics within the field of women's health, we were interested in potential gaps related to geographic and racial and ethnic diversity. We also aimed to understand the degree of inclusion of women with progressive MS in this research., Methods: We searched the EMBASE and Ovid Medline databases from 1980 until November 23, 2020. We included case-control and cohort studies, clinical trials and case series published in any language, conducted in women with MS, clinically isolated syndrome, or radiologically isolated syndrome, that addressed women's health. Two reviewers independently screened abstracts and full-text reports for study inclusion, and completed data extraction., Results: Of 112,106 citations screened, 1,041 underwent full-text review and 353 met the inclusion criteria. The number of studies regarding women's health has increased exponentially over time. Almost half of the studies were conducted (at least in part) in Europe, while 21.7% were conducted in North America; only one study was conducted in Africa. Most studies did not report the race or ethnicity of their participants ( n = 308, 87.2%). Among the 353 studies, 509 topics were reported as some studies addressed more than one topic. Over one-third of these focused on pregnancy ( n = 201, 37.2%), followed by fetal/neonatal outcomes (14.4%) and sexual dysfunction (10%). Among the 201 studies that focused on pregnancy, only 51 (25.4%) included participants with progressive MS., Conclusions: This review identifies important knowledge gaps related to women's health in MS and particularly the need for future studies to include participants with a broader range of races and ethnicities, with progressive MS, and living in Asia-Pacific and African regions., Competing Interests: LR received funding from the National MS Society Sylvia Lawry Physician Fellowship. HN receives funding from the Multiple Sclerosis Society of Canada's end MS Post-doctoral Fellowship, and the Michael Smith Foundation for Health Research Trainee Award. MA served on Scientific Advisory Boards for Biogen, Novartis, Roche, Merck, Sanofi Genzyme and Teva; received speaker honoraria from Biogen, Merck, Sanofi Genzyme, Roche, Novartis and Teva; received research grants for her Institution from Biogen, Merck, Sanofi Genzyme, Novartis and Roche. She is co-editor of the Multiple Sclerosis Journal. JC received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaking for H3 Communications; and serving as an Editor of Multiple Sclerosis Journal. KH received personal compensation as a speaker for Biogen, Bristol-Myers Squibb, Roche, Teva, Novartis, Bayer, Sanofi-Genzyme and Merck. She receives currently funding by the Innovationsfonds, the national MS society, Biogen, Teva, Novartis, Roche, Sanofi-Genzyme and Merck. MT has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals. SV received consulting and lecture fees, travel grants and research support from Biogen, Celgène/BMS, Novartis, Merck, Roche, Sanofi Genzyme and Teva Pharma. RM receives research funding from CIHR, the MS Society of Canada, the National MS Society, the Consortium of MS Centers, the US Department of Defense, Research Manitoba and Crohn's and Colitis Canada. She was supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on studies funded by Biogen Idec and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ross, Ng, O'Mahony, Amato, Cohen, Harnegie, Hellwig, Tintore, Vukusic and Marrie.)
Published: 2022
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