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192 results on '"Kister I"'

2. Treatment of MOG antibody associated disorders: results of an international survey

Author

Whittam, D. H., Karthikeayan, V., Gibbons, E., Kneen, R., Chandratre, S., Ciccarelli, O., Hacohen, Y., de Seze, J., Deiva, K., Hintzen, R. Q., Wildemann, B., Jarius, S., Kleiter, I., Rostasy, K., Huppke, P., Hemmer, B., Paul, F., Aktas, O., Pröbstel, A. K., Arrambide, G., Tintore, M., Amato, M. P., Nosadini, M., Mancardi, M. M., Capobianco, M., Illes, Z., Siva, A., Altintas, A., Akman-Demir, G., Pandit, L., Apiwattankul, M., Hor, J. Y., Viswanathan, S., Qiu, W., Kim, H. J., Nakashima, I., Fujihara, K., Ramanathan, S., Dale, R. C., Boggild, M., Broadley, S., Lana-Peixoto, M. A., Sato, D. K., Tenembaum, S., Cabre, P., Wingerchuk, D. M., Weinshenker, B. G., Greenberg, B., Matiello, M., Klawiter, E. C., Bennett, J. L., Wallach, A. I., Kister, I., Banwell, B. L., Traboulsee, A., Pohl, D., Palace, J., Leite, M. I., Levy, M., Marignier, R., Solomon, T., Lim, M., Huda, S., and Jacob, A.

Published
2020
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4. Multiple Sclerosis Severity Score (MSSS) improves the accuracy of individualized prediction in MS

Author

Kalincik, T, Kister, I, Bacon, TE, Malpas, CB, Sharmin, S, Horakova, D, Kubala-Havrdova, E, Patti, F, Izquierdo, G, Eichau, S, Ozakbas, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Sola, P, Ferraro, D, Alroughani, R, Terzi, M, Boz, C, Grand'Maison, F, Bergamaschi, R, Gerlach, O, Sa, MJ, Kappos, L, Cartechini, E, Lechner-Scott, J, van Pesch, V, Shaygannejad, V, Granella, F, Spitaleri, D, Iuliano, G, Maimone, D, Prevost, J, Soysal, A, Turkoglu, R, Ampapa, R, Butzkueven, H, Cutter, G, Kalincik, T, Kister, I, Bacon, TE, Malpas, CB, Sharmin, S, Horakova, D, Kubala-Havrdova, E, Patti, F, Izquierdo, G, Eichau, S, Ozakbas, S, Onofrj, M, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Sola, P, Ferraro, D, Alroughani, R, Terzi, M, Boz, C, Grand'Maison, F, Bergamaschi, R, Gerlach, O, Sa, MJ, Kappos, L, Cartechini, E, Lechner-Scott, J, van Pesch, V, Shaygannejad, V, Granella, F, Spitaleri, D, Iuliano, G, Maimone, D, Prevost, J, Soysal, A, Turkoglu, R, Ampapa, R, Butzkueven, H, and Cutter, G

Abstract

BACKGROUND: The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. OBJECTIVE: To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. METHODS: The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients' demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. RESULTS: A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. CONCLUSION: Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.

Published
2022

5. Long-term outcomes in patients presenting with optic neuritis: analyses of the MSBase registry

Author

Horakova, D., Granella, F., Grand-Maison, F., ÖZAKBAŞ, SERKAN, Bergamaschi, R., Ampapa, R., Alroughani, R., Liu, M., Kenney, R., Turkoglu, R., Terzi, M., Spitaleri, D. L. A., Soysal, A., Sola, P., Preiningerova, J. Lizrova, Patti, F., Onofrj, M., Lugaresi, A., Kalincik, T., Ayuso, G. Izquierdo, Galetta, S., Balcer, L., Kister, I., Spelman, T., Madueno, S. Eichau, Ferraro, D., Boz, C., Butzkueven, H., Gomez, J. Cabrera, Cartechini, E., Thorpe, L., Saidha, S., and Van Pesch, V.

Published
2021

6. PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder cohort description

Author

Chien, C., Silva, V. Cruz, Geiter, E., Zimmermann, H., Specovius, S., Oertel, F. C., Bichuetti, D. B., Idagawa, M., Altintas, A., Tanriverdi, U., Siritho, S., Pandit, L., Dcunha, A., Sa, M. J., Figueiredo, R., Tongco, C., Qian, P., Lotan, I., Khasminsky, V., Hellmann, M., Stiebel-Kalish, H., Rotstein, D., Waxman, L., Ontaneda, D., Nakamura, K., Abboud, H., Subei, M. O., Mao-Draayer, Y., Havla, J., Asgari, N., Skejo, P., Kister, I., Rimler, Z., Reid, A., Ringelstein, M., Broadley, S., Arnett, S., Marron, B., Jolley, A., Wunderlich, M., Green, S., Cook, L., Yeaman, M. R., Smith, T. J., Brandt, A. U., Wuerfel, J., Paul, F., and NMOSD, GICC

Published
2021
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8. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.

Author

Van Pesch V., Eichau S., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Giuliano F., Mcguigan C., Cartechini E., Barnett M., Hughes S., Sa M., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., Mccombe P., Ampapa R., Skibina O., Prevost J., Sinnige L.G.F., Sanchez-Menoyo J.L., Vucic S., Laureys G., Van Hijfte L., Khurana D., Macdonell R., Castillo-Trivino T., Gray O., Aguera E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Izquierdo G., Van Pesch V., Eichau S., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Giuliano F., Mcguigan C., Cartechini E., Barnett M., Hughes S., Sa M., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., Mccombe P., Ampapa R., Skibina O., Prevost J., Sinnige L.G.F., Sanchez-Menoyo J.L., Vucic S., Laureys G., Van Hijfte L., Khurana D., Macdonell R., Castillo-Trivino T., Gray O., Aguera E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., and Izquierdo G.

Abstract

Background: Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited. Objective(s): To assess whether patients' response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Method(s): Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, pro

Published
2021

9. Variability of the Response to Immunotherapy among Sub-groups of Patients with Multiple Sclerosis.

Author

Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., and Kalincik T.

Abstract

Objective: To assess whether patients' response to disease modifying therapies (DMT) in multiple sclerosis (MS) varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Background(s): Our understanding of demographic and clinical modifiers of the effectiveness of MS therapies is limited. Design/Methods: Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. Models were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23687 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence [HR=0.52 (0.44-0.61)], 48% lower risk of disability worsening [HR=0.52 (0.38-0.71)] and 33% greater chance of disability improvement [HR=1.33 (95%CI 1.0-1.5)]. The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The effect of DMTs on reducing relapses declined with higher prior relapse rate and in patients with prior cerebral MRI activity. Among 26329 participants with relapsing or progressive MS, DMTs were associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR=0.75 (0.65-0.86) and HR=0.58 (0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR=1.11 (0.91-1.46) and HR=1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. The DMTs are most effective among patients with lower

Published
2021

12. Predicting long-term sustained disability progression in multiple sclerosis.

Author

Van Wijmeersch B., Malpas C., Hupperts R.M.M., Alroughani R., Boz C., Shaygannejad V., Van Pesch V., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Ramo-Tello C., Iuliano G., Granella F., Spitaleri D.L.A., Bolanos R.F., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J.L., Soysal A., Vucic O., Petersen T., Verheul F., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Urtaza F.J.O., Saladino M.L., Barnett M., Deri N., Moore F., Rozsa C., Yamout B., Skibina O., Gray O., Campbell J., Sempere A., Singhal B., Fragoso Y., Shaw C., Kermode A., Petkovska-Boskova T., Taylor B., Simo M., Vella N., Shuey N., Alkhaboori J., Al-Harbi T., Macdonell R., Dominguez J.A., Kister I., Csepany T., Vrech C., Kovacs K., Sirbu C.A., Hughes S., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Horakova D., Havrdova E., Ayuso G.I., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., Terzi M., Van Wijmeersch B., Malpas C., Hupperts R.M.M., Alroughani R., Boz C., Shaygannejad V., Van Pesch V., Kappos L., Lechner-Scott J., Bergamaschi R., Turkoglu R., Solaro C., Ramo-Tello C., Iuliano G., Granella F., Spitaleri D.L.A., Bolanos R.F., Slee M., McCombe P., Prevost J., Ampapa R., Ozakbas S., Sanchez-Menoyo J.L., Soysal A., Vucic O., Petersen T., Verheul F., Butler E., Hodgkinson S., Sidhom Y., Gouider R., Cristiano E., Urtaza F.J.O., Saladino M.L., Barnett M., Deri N., Moore F., Rozsa C., Yamout B., Skibina O., Gray O., Campbell J., Sempere A., Singhal B., Fragoso Y., Shaw C., Kermode A., Petkovska-Boskova T., Taylor B., Simo M., Vella N., Shuey N., Alkhaboori J., Al-Harbi T., Macdonell R., Dominguez J.A., Kister I., Csepany T., Vrech C., Kovacs K., Sirbu C.A., Hughes S., Sormani M.P., Butzkueven H., Kalincik T., Sharmin S., Bovis F., Horakova D., Havrdova E., Ayuso G.I., Eichau S., Trojano M., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Grammond P., Sola P., Ferraro D., and Terzi M.

Abstract

Objective: Using global MSBase registry, this study establishes 6-month confirmed disability progression events as indicators of long-term disability worsening suitable for use in randomized clinical trials in multiple sclerosis (MS). Background(s): Randomized clinical trials evaluate short-term treatment effect on disability in the form of 3-6-month confirmed disability progression, but whether these translate into long-term disability outcomes is unknown. Design/Methods: A Cox proportional hazards model identified associations between patients' demographic and clinical characteristics and the probability of recovery from disability progression events. The coefficients from this model were used to calculate a sustained progression score, which was evaluated in a validation cohort and applied to a trial cohort. Result(s): 902 patients (development cohort), patient characteristics at the time of progression associated with lower probability of subsequent improvement were age (hazard ratio (HR)=0.98), primary progressive (HR=0.37) and progressive-relapsing (HR=0.36) MS, expanded disability status scale score >=6 (HR=0.71) and its change from baseline (HR=0.67), number of affected functional system scores (HR=0.92) and pyramidal (HR=0.79) functional system score (p<0.05). The strength of the association with pyramidal score decreased with time (HR=1.01). A relapse within previous month (HR=1.46) and worsening in sensory functional system score (HR=1.17) were associated with higher probability of improvement after progression. The sustained progression score (range 0.39-4.79) in the validation cohort with 1,271 progression events, estimated a 53% lower chance of improvement for each unit increase in the score (HR=0.47). The proportions of progression events sustained at 5 years stratified by the score were 1: 68%, 2: 79%, 3: 94%, 4: 100%. The progression scores were then applied to the CLARITY trial data. Conclusion(s): Estimate of the probability of disability progress

Published
2020

13. Multiple Sclerosis Severity Score (MSSS) helps predict relapses and recovery from disability in patients treated for multiple sclerosis in the MSBase model

Author

Kister, I., Bacon, T. E., Malpas, C. B., Sharmin, S., Horakova, D., Havrdova, E. K., Sa, M. J., and Ondokuz Mayıs Üniversitesi

Abstract

35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS -- SEP 11-13, 2019 -- Stockholm, SWEDEN Turkoglu, Recai/0000-0001-9724-851X; Ferraro, Diana/0000-0003-4818-3806; WOS: 000485303100308 … European Comm Treatment & Res Multiple Sclerosis, Congrex Switzerland Ltd BiogenBiogen; Czech Minsitry of Education [Q27/LF1] Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, as well as support for research activities from Biogen and Czech Minsitry of Education [project Progres Q27/LF1].; Eva Kubala Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education [project Progres Q27/LF1].

Published
2019

14. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

Author

Brown J, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A, Girard M, Duquette P, Trojano M, Lugaresi A, Bergamaschi R, Grammond P, Alroughani R, Hupperts R, McCombe P, Van Pesch V, Sola P, Ferraro D, Grand'Maison F, Terzi M, Lechner-Scott J, Flechter S, Slee M, Shaygannejad V, Pucci E, Granella F, Jokubaitis V, Willis M, Rice C, Scolding N, Wilkins A, Pearson O, Ziemssen T, Hutchinson M, Harding K, Jones J, McGuigan C, Butzkueven H, Kalincik T, Robertson N, Onofrj M, De Luca G, Di Tommaso V, Travaglini D, Pietrolongo E, di Ioia M, Farina D, Mancinelli L, Hodgkinson S, Oreja-Guevara C, Boz C, Prevost J, Olascoaga J, Van Wijmeersch B, Barnett M, Verheul F, Rojas J, Spitaleri D, Rio M, Taylor B, Sanchez-Menoyo J, Ramo-Tello C, Solaro C, Csepany T, Iuliano G, Skibina O, Petersen T, Bolanos R, Sidhom Y, Riadh, Vucic S, Macdonell R, Sempere A, Simo M, Kister I, Shuey N, Radek, Dominguez J, Amato M, Saladino M, Kermode A, Butler E, Moore F, Hughes S, McDonnell G, Piroska I, Yamout B, Soysal A, Ozakbas S, Zwanikken C, and MSBase Study Grp

Abstract

IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS. RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P

Published
2019

15. The CROCTINO project: an international retrospective multi-center study of retinal optical coherence tomography in 501 patients with neuromyelitis optica spectrum disorders

Author

Specovius, S., Zimmermann, H. G., Chien, C., Oertel, F. C., Cooke, L., Martinez-Lapiscina, E. H., Lana-Peixoto, M. A., Fontenelle, M. A., Palaces, J., Roca-Fernandez, A., Diaz, A. Rubio, Leiter, M. I., Sharma, S. M., Siritho, S., Altintas, A., Yildirim, R., Tanriverdi, U., Jacob, A., Huda, S., Marignier, R., Nerrant, E., Cobo-Calvo, A., de Seze, J., Senger, T., Pandit, L., Dcunha, A., Soto de Castillo, I., Bichuetti, D., Maynart Tavares, I., May, E. F., Tongco, C., Havla, J., Leocani, L., Pisa, M., Radaelli, M., Aktas, O., Ringelstein, M., Rybak, J., Albrecht, P., Kim, H. J., Hyun, J. -W., Asgari, N., Soelberg, K., Mao-Draayer, Y., Stiebel-Kalish, H., Kister, I., Rimler, Z., Reid, A., Brandt, A. U., Paul, F., and [Unknown], GJCF-ICC

Published
2018

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

Author

Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), Terzi M., Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), and Terzi M.

Abstract

Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative

Published
2018

17. Predictors of relapses and disability progression after stopping disease-modifying therapies for multiple sclerosis

Author

Kister, I., Spelman, T., Patti, F., Duquette, P., Trojano, M., Izquierdo, G., Butzkueven, H., and Ondokuz Mayıs Üniversitesi

Abstract

7th Joint European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)-Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) -- OCT 25-28, 2017 -- Paris, FRANCE Ferraro, Diana/0000-0003-4818-3806; Lugaresi, Alessandra/0000-0003-2902-5589 WOS: 000413730202114 … European Comm Treatment & Res Multiple Sclerosis, Americas Comm Treatment & Res Multiple Sclerosis Biogen IncBiogen; Biogen-IdecBiogen; Merck SeronoMerck SeronoMerck & Company; NovartisNovartis; BayerBayer AG; BiogenBiogen; MerckMerck & Company; SanofiSanofi-Aventis; Teva; Associazione Italiana Sclerosi MultiplaFondazione Italiana Sclerosi Multipla (FISM); Teva-neuroscience; Canadian Multiple Sclerosis Society; Bayer ScheringBayer AG; Sanofi/Genzyme; Sanofi-Genzyme; GenzymeGenzyme Corporation; Teva Neurosciences; Mitsubishi; ONO Pharmaceuticals; Merck-SeronoMerck SeronoMerck & Company; Actelion; Addex; Bayer HealthCareBayer AGBayer Healthcare Pharmaceuticals; Biotica; LillyEli Lilly; Ono Pharma; PfizerPfizer; Receptos; Sanofi-AventisSanofi-Aventis; Santhera; Siemens; UCBUCB Pharma SA; Xenoport; CSL Behring; European UnionEuropean Union (EU); RocheRoche Holding; Roche Research Foundations; Swiss MS Society; Swiss National Research FoundationSwiss National Science Foundation (SNSF); Sanofi AventisSanofi-Aventis; LundbeckLundbeck Corporation; Associazone Marchigana Sclerosi Multipla e altre malattie neurologiche; Biogen IdecBiogen; FISM (Fondazione Italiana Sclerosi Multipla)Fondazione Italiana Sclerosi Multipla (FISM) Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc and speaker honoraria from Novartis.; Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva, Novartis and Almirall; has received research grants for her institution from Biogen-Idec, Merck Serono and Novartis.; Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi and Teva, research grants from the Associazione Italiana Sclerosi Multipla.; Pierre Grammond is a Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-neuroscience and Canadian Multiple Sclerosis Society, and received grants for travel from Teva-neuroscience and Novartis.; Patrizia Sola received travel grants and speaking honoraria from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi/Genzyme and Teva.; Diana Ferraro received travel grants and/or speaker honoraria from Merck Serono, Biogen, TEVA, Novartis, Sanofi-Genzyme.; Francois Grand'Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.; Murat Terzi received travel grants from Merck Serono, Novartis, Bayer Schering and Teva and has participated in clinical trials by Sanofi-Aventis, Roche and Novartis.; Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.; Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen, CSL, Genzyme Sanofi, Merck Serono and Novartis.; Ludwig Kappos's institution (University Hospital, Basel) received in the last 3 years and used exclusively for research support: steering committee, advisory board and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis and Teva; royalties from Neurostatus Systems GmbH; and grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, Swiss MS Society and the Swiss National Research Foundation.; Eugenio Pucci served on scientific advisory boards for Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck Serono, Genzyme and Teva; he has received travel grants from Associazone Marchigana Sclerosi Multipla e altre malattie neurologiche.; Suzanne Hodgkinson received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering.; Claudio Solaro served as a member of the advisory board of the following companies: Biogen Idec and Merck Serono; received speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Teva, Almirall, and Sanofi Genzyme and research grants and support by the FISM (Fondazione Italiana Sclerosi Multipla); Helmut Butzkueven served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committes for trials conducted by Biogen and Novartis, and has received research support from Merck Serono, Novartis and Biogen.

Published
2017

18. Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

Author

Schumacher, S., Pache, F., Bellmann-Strobl, J., Behrens, J., Dusek, P., Harms, L., Ruprecht, K., Nytrova, P., Chawla, S., Niendorf, T., Kister, I., Paul, F., Ge, Y., Wuerfel, J., and Sinnecker, T.

Subjects
Cardiovascular and Metabolic Diseases, Function and Dysfunction of the Nervous System
Abstract

Objective: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. Materials and methods: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. Results: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). Conclusion: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system.

Published
2016

19. Contribution of different relapse phenotypes to disability in multiple sclerosis

Author

Stewart, T., Spelman, T., Havrdova, E., Horakova, D., Trojano, M., Izquierdo, G., Duquette, P., Girard, M., Prat, A., Lugaresi, A., Grand’Maison, F., Grammond, P., Sola, P., Shaygannejad, V., Hupperts, R., Alroughani, R., Oreja-Guevara, C., Pucci, E., Boz, C., Lechner-Scott, J., Bergamaschi, R., van Pesch, V., Iuliano, G., Ramo, C., Taylor, B., Slee, M., Spitaleri, D., Granella, F., Verheul, F., McCombe, P., Hodgkinson, S., Amato, M.P., Vucic, S., Gray, O., Cristiano, E., Barnett, M., Sanchez Menoyo, J.L., van Munster, E., Saladino, M.L., Olascoaga, J., Prevost, J., Deri, N., Shaw, C., Singhal, B., Moore, F., Rózsa, C., Shuey, N., Skibina, O., Kister, I., Petkovska-Boskova, T., Ampapa, R., Kermode, A., Butzkueven, H., Jokubaitis, V., Kalincik, T., Stewart, T., Spelman, T., Havrdova, E., Horakova, D., Trojano, M., Izquierdo, G., Duquette, P., Girard, M., Prat, A., Lugaresi, A., Grand’Maison, F., Grammond, P., Sola, P., Shaygannejad, V., Hupperts, R., Alroughani, R., Oreja-Guevara, C., Pucci, E., Boz, C., Lechner-Scott, J., Bergamaschi, R., van Pesch, V., Iuliano, G., Ramo, C., Taylor, B., Slee, M., Spitaleri, D., Granella, F., Verheul, F., McCombe, P., Hodgkinson, S., Amato, M.P., Vucic, S., Gray, O., Cristiano, E., Barnett, M., Sanchez Menoyo, J.L., van Munster, E., Saladino, M.L., Olascoaga, J., Prevost, J., Deri, N., Shaw, C., Singhal, B., Moore, F., Rózsa, C., Shuey, N., Skibina, O., Kister, I., Petkovska-Boskova, T., Ampapa, R., Kermode, A., Butzkueven, H., Jokubaitis, V., and Kalincik, T.

Abstract

Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. Results: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (β = 0.27 (0.25–0.29)), cerebellar (β = 0.35 (0.30–0.39)) and bowel/bladder (β = 0.42 (0.35–0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains. Conclusion: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.

Published
2017

20. SymptoMScreen

Author

Green, R., primary, Kalina, J., additional, Ford, R., additional, Pandey, K., additional, and Kister, I., additional

Published
2017
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21. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis

Author

Warrender-Sparkes, M, Spelman, T, Izquierdo, G, Trojano, M, Lugaresi, A, Grand'Maison, F, Havrdova, E, Horakova, D, Boz, C, Oreja-Guevara, C, Alroughani, R, Iuliano, G, Duquette, P, Girard, M, Terzi, M, Hupperts, R, Grammond, P, Petersen, T, Fernandez-Bolanos, R, Fiol, M, Pucci, E, Lechner-Scott, J, Verheul, F, Cristiano, E, Van Pesch, V, Petkovska-Boskova, T, Moore, F, Kister, I, Bergamaschi, R, Laura Saladino, M, Slee, M, Barnett, M, Amato, MP, Shaw, C, Shuey, N, Young, C, Gray, O, Kappos, L, Butzkueven, H, Kalincik, T, Jokubaitis, V, Warrender-Sparkes, M, Spelman, T, Izquierdo, G, Trojano, M, Lugaresi, A, Grand'Maison, F, Havrdova, E, Horakova, D, Boz, C, Oreja-Guevara, C, Alroughani, R, Iuliano, G, Duquette, P, Girard, M, Terzi, M, Hupperts, R, Grammond, P, Petersen, T, Fernandez-Bolanos, R, Fiol, M, Pucci, E, Lechner-Scott, J, Verheul, F, Cristiano, E, Van Pesch, V, Petkovska-Boskova, T, Moore, F, Kister, I, Bergamaschi, R, Laura Saladino, M, Slee, M, Barnett, M, Amato, MP, Shaw, C, Shuey, N, Young, C, Gray, O, Kappos, L, Butzkueven, H, Kalincik, T, and Jokubaitis, V

Abstract

OBJECTIVE: We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). METHODS: MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. RESULTS: A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation. CONCLUSION: Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications.

Published
2016

24. Extended interval dosing of natalizumab in multiple sclerosis

Author

Zhovtis Ryerson, L, primary, Frohman, T C, additional, Foley, J, additional, Kister, I, additional, Weinstock-Guttman, B, additional, Tornatore, C, additional, Pandey, K, additional, Donnelly, S, additional, Pawate, S, additional, Bomprezzi, R, additional, Smith, D, additional, Kolb, C, additional, Qureshi, S, additional, Okuda, D, additional, Kalina, J, additional, Rimler, Z, additional, Green, R, additional, Monson, N, additional, Hoyt, T, additional, Bradshaw, M, additional, Fallon, J, additional, Chamot, E, additional, Bucello, M, additional, Beh, S, additional, Cutter, G, additional, Major, E, additional, Herbert, J, additional, and Frohman, E M, additional

Published
2016
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26. Multiple sclerosis in Latin America: A different disease course severity? A collaborative study from the MSBase Registry

Author

Rojas, JI, Patrucco, L, Trojano, M, Lugaresi, A, Izquierdo, G, Butzkueven, H, Jokubaitis, V, Duquette, P, Girard, M, Grand’Maison, F, Grammond, P, Oreja-Guevara, C, Hupperts, R, Boz, C, Petersen, T, Bergamaschi, R, Giuliani, G, Lechner-Scott, J, Barnett, M, Rio, ME, Van Pesch, V, Amato, MP, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Fernandez-Bolanos, R, Poehlau, D, Saladino, ML, Braber-Moerland, LD, Deri, N, Oleschko-Arruda, W, Cabrera-Gomez, JA, Paine, M, Vella, N, Kister, I, Skromne, E, Savino, A, Shaw, Cameron, Moore, F, Vucic, S, Petkovska-Boskova, T, Bacile, EAB, Santiago, V, Cristiano, E, Rojas, JI, Patrucco, L, Trojano, M, Lugaresi, A, Izquierdo, G, Butzkueven, H, Jokubaitis, V, Duquette, P, Girard, M, Grand’Maison, F, Grammond, P, Oreja-Guevara, C, Hupperts, R, Boz, C, Petersen, T, Bergamaschi, R, Giuliani, G, Lechner-Scott, J, Barnett, M, Rio, ME, Van Pesch, V, Amato, MP, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Fernandez-Bolanos, R, Poehlau, D, Saladino, ML, Braber-Moerland, LD, Deri, N, Oleschko-Arruda, W, Cabrera-Gomez, JA, Paine, M, Vella, N, Kister, I, Skromne, E, Savino, A, Shaw, Cameron, Moore, F, Vucic, S, Petkovska-Boskova, T, Bacile, EAB, Santiago, V, and Cristiano, E

Abstract

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. Methods Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed. Results A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres ( p = 0.68), regions ( p = 0.96) or countries ( p = 0.50). Conclusions Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.

Published
2015

28. SymptoMScreen: A Tool for Rapid Assessment of Symptom Severity in MS Across Multiple Domains.

Author

Green, R., Kalina, J., Ford, R., Pandey, K., and Kister, I.

Subjects
MULTIPLE sclerosis, MEDICAL screening, TEST validity, DIAGNOSTIC examinations, SYMPTOMS, PROGNOSIS, MULTIPLE sclerosis diagnosis, PSYCHOMETRICS, NEUROPSYCHOLOGICAL tests, RESEARCH evaluation, SEVERITY of illness index, EQUIPMENT & supplies
Abstract

The objective of this study was to describe SymptoMScreen, an in-house developed tool for rapid assessment of MS symptom severity in routine clinical practice, and to validate SymptoMScreen against Performance Scales (PS). MS patients typically experience symptoms in many neurologic domains. A tool that would enable MS patients to efficiently relay their symptom severity across multiple domains to the healthcare providers could lead to improved symptom management. We developed “SymptoMScreen,” a battery of 7-point Likert scales for 12 distinct domains commonly affected by MS: mobility, dexterity, body pain, sensation, bladder function, fatigue, vision, dizziness, cognition, depression, and anxiety. We administered SymptoMScreen and PS scales to consecutive MS patients at a specialty MS Care Center. We assessed the criterion and construct validity of SymptoMScreen by calculating Spearmen rank correlations between the SymptoMScreen composite score and PS composite score, and between SymptoMScreen subscale and the respective PS subscale scores, where applicable. A total of 410 patients with MS (age 46.6 ± 12.9 years; 74% female; mean disease duration 12.2 ± 8.7 years) completed the SymptoMScreen and PSs during their clinic visit. Composite SymptoMScreen score correlated strongly with combined PS score (r = 0.88,p < 0.0001). SymptoMScreen sub scores correlated strongly with the criterion measures of the respective PS (r = 0.69–0.87,p < 0.0001). Test-retest reliability of SymptoMScreen and its subscales was excellent (r = 0.71–0.94,p < .0001). SymptoMScreen is a single-page battery of Likert scales that assesses symptom impact in 12 domains commonly affected in MS. It has excellent criterion and construct validity. SymptoMScreen is patient and clinician friendly, takes approximately one minute to complete, and can help better document, understand, and manage patients’ symptoms in routine clinical practice. SymptoMScreen is freely available to clinicians and researchers. [ABSTRACT FROM PUBLISHER]

Published
2017
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38. Rapid disease course in African Americans with multiple sclerosis

Author

Kister, I., primary, Chamot, E., additional, Bacon, J. H., additional, Niewczyk, P. M., additional, De Guzman, R. A., additional, Apatoff, B., additional, Coyle, P., additional, Goodman, A. D., additional, Gottesman, M., additional, Granger, C., additional, Jubelt, B., additional, Krupp, L., additional, Lenihan, M., additional, Lublin, F., additional, Mihai, C., additional, Miller, A., additional, Munschauer, F. E., additional, Perel, A. B., additional, Teter, B. E., additional, Weinstock-Guttman, B., additional, Zivadinov, R., additional, and Herbert, J., additional

Published
2010
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42. Timing of high-efficacy therapy for multiple sclerosis:a retrospective observational cohort study

Author

Francois Grand'Maison, Alessandra Lugaresi, Christopher McGuigan, Pierre Grammond, Helmut Butzkueven, Ilya Kister, Bernd Merkel, Maria Trojano, Franco Granella, Vincent Van Pesch, Eva Havrdova, Lana Zhovits Ryerson, Anders Svenningsson, Thor Petersen, Jan Lycke, Catherine Larochelle, Jan Hillert, Fredrik Piehl, Guillermo Izquierdo, Alasdair Coles, Tim Spelman, Charles B Malpas, Patrizia Sola, James William L Brown, Dana Horakova, Tomas Kalincik, Marc Girard, Pierre Duquette, Alexandre Prat, Raymond Hupperts, Sifat Sharmin, Diana Ferraro, Sara Eichau, Roberto Bergamaschi, Anna He, He A., Merkel B., Brown J.W.L., Zhovits Ryerson L., Kister I., Malpas C.B., Sharmin S., Horakova D., Kubala Havrdova E., Spelman T., Izquierdo G., Eichau S., Trojano M., Lugaresi A., Hupperts R., Sola P., Ferraro D., Lycke J., Grand'Maison F., Prat A., Girard M., Duquette P., Larochelle C., Svenningsson A., Petersen T., Grammond P., Granella F., Van Pesch V., Bergamaschi R., McGuigan C., Coles A., Hillert J., Piehl F., Butzkueven H., and Kalincik T.

Subjects
Adult, Male, Registrie, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Disease, Follow-Up Studie, Time-to-Treatment, Cohort Studies, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Retrospective Studie, Multiple Sclerosi, medicine, Humans, 030212 general & internal medicine, Registries, Age of Onset, Propensity Score, Retrospective Studies, Sweden, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Treatment Outcome, Propensity score matching, Alemtuzumab, Observational study, Ocrelizumab, Female, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study, Follow-Up Studies, Human
Abstract

Background: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4–6 years after disease onset. Methods: In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0–2 years (early) or 4–6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0–10, with higher scores indicating increased disability), at 6–10 years after disease onset, assessed with a linear mixed-effects model. Findings: We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7–8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p

Published
2020
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43. Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry

Author

Kenney, Rachel, Liu, Mengling, Patil, Sachi, Alroughani, Raed, Ampapa, Radek, Bergamaschi, Roberto, Boz, Cavit, Butzkueven, Helmut, Gomez, Jose Cabrera, Cartechini, Elisabetta, Madueño, Sara Eichau, Ferraro, Diana, Grand-Maison, Francois, Granella, Franco, Horakova, Dana, Izquierdo Ayuso, Guillermo, Kalincik, Tomas, Lizrova Preiningerova, Jana, Lugaresi, Alessandra, Onofrj, Marco, Ozakbas, Serkan, Patti, Francesco, Sola, Patrizia, Soysal, Aysun, Spitaleri, Daniele Litterio A, Terzi, Murat, Turkoglu, Recai, Van Pesch, Vincent, Saidha, Shiv, Thorpe, Lorna E, Galetta, Steven L, Balcer, Laura J, Kister, Ilya, Spelman, Tim, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kenney R., Liu M., Patil S., Alroughani R., Ampapa R., Bergamaschi R., Boz C., Butzkueven H., Gomez J.C., Cartechini E., Madueno S.E., Ferraro D., Grand-Maison F., Granella F., Horakova D., Izquierdo Ayuso G., Kalincik T., Lizrova Preiningerova J., Lugaresi A., Onofrj M., Ozakbas S., Patti F., Sola P., Soysal A., Spitaleri D.L.A., Terzi M., Turkoglu R., van Pesch V., Saidha S., Thorpe L.E., Galetta S.L., Balcer L.J., Kister I., and Spelman T.

Subjects
Registrie, Adult, Optic neuriti, medicine.medical_specialty, Multiple Sclerosis, Optic Neuritis, Adolescent, Expanded disability status scale (EDSS), Vision, Cohort Studies, Disability Evaluation, Young Adult, Internal medicine, Multiple Sclerosi, medicine, Humans, Optic neuritis, Registries, Young adult, Survival analysis, Clinically isolated syndrome, Expanded Disability Status Scale, business.industry, Demyelinating Disease, medicine.disease, Clinical research, MSBase registry, Neurology, Cohort, Disease Progression, Female, Neurology (clinical), Cohort Studie, business, Human, Demyelinating Diseases, Cohort study
Abstract

Background: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. Methods: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. Results: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1–2), and median VFS was 1 (IQR 0–2). Median follow-up time was 5.2 years (IQR 2.4–9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. Conclusions: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.

Published
2021
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44. Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Author

Guillermo Izquierdo, Ayse Altintas, Tomas Kalincik, Petra Nytrova, Charles B Malpas, Roberto Bergamaschi, Ilya Kister, Diana Ferraro, Aysun Soysal, Helmut Butzkueven, Sara Eichau, Francois Grand'Maison, Guy Laureys, Jeannette Lechner-Scott, Jyh Yung Hor, Pamela A. McCombe, Yara Dadalti Fragoso, Steve Vucic, Rana Karabudak, Raed Alroughani, Cavit Boz, Celia Oreja-Guevara, Eugenio Pucci, Tünde Csépány, Patrizia Sola, Serkan Ozakbas, Bhim Singhal, Francesco Patti, Maria Trojano, Franco Granella, Marco Onofrj, Alessandra Lugaresi, Recai Turkoglu, Mark Marriott, Murat Terzi, Amy Kunchok, Talal Al-Harbi, Magdolna Simó, Javier Olascoaga, Eva Havrdova, Bassem Yamout, Kunchok A., Malpas C., Nytrova P., Havrdova E.K., Alroughani R., Terzi M., Yamout B., Hor J.Y., Karabudak R., Boz C., Ozakbas S., Olascoaga J., Simo M., Granella F., Patti F., McCombe P., Csepany T., Singhal B., Bergamaschi R., Fragoso Y., Al-Harbi T., Turkoglu R., Lechner-Scott J., Laureys G., Oreja-Guevara C., Pucci E., Sola P., Ferraro D., Altintas A., Soysal A., Vucic S., Grand'Maison F., Izquierdo G., Eichau S., Lugaresi A., Onofrj M., Trojano M., Marriott M., Butzkueven H., Kister I., Kalincik T., and Ondokuz Mayıs Üniversitesi

Subjects
Male, Time Factors, Azathioprine, Severity of Illness Index, 0302 clinical medicine, Natalizumab, Recurrence, Outcome Assessment, Health Care, Disability, Immunosuppression, Neuromyelitis optica spectrum disorder, Predictors, Relapses, Therapy, 030212 general & internal medicine, Registries, Relapse, Hazard ratio, Neuromyelitis Optica, Age Factors, General Medicine, Middle Aged, Neurology, Cohort, Disease Progression, Female, Rituximab, medicine.drug, Cohort study, Adult, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Humans, Immunologic Factors, Aquaporin 4, Neuromyelitis optica, Expanded Disability Status Scale, Proportional hazards model, business.industry, Mycophenolic Acid, medicine.disease, Immunoglobulin G, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, Predictor
Abstract

Altintas, Ayse/0000-0002-8524-5087; Laureys, Guy/0000-0002-1708-4373; Vucic, Steve/0000-0002-8323-873X; patti, francesco/0000-0002-6923-0846; Kister, Ilya/0000-0003-3549-949X; Lugaresi, Alessandra/0000-0003-2902-5589 WOS: 000521648000049 PubMed: 31877445 Background: Aquaporin-4-IgG positive (AQP4-IgG(+)) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG + NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG + NMOSD. Method: This MSBase cohort study of AQP4-IgG + NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. Results: 206 AQP4-IgG + patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p < 0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (beta = 0.45 (per decade), p < 0.001) and disease duration (beta = 0.07 per year, p < 0.001). A slower increase in EDSS was associated with azathioprine (beta = -0.48, p < 0.001), mycophenolate mofetil (beta = -0.69, p = 0.04) and rituximab (beta = -0.35, p = 0.024). Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort. National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1083539, 1129189, 1140766, 1080518]; MerckMerck & Company; BiogenBiogen; NovartisNovartis; Bayer-ScheringBayer AG; Sanofi-Genzyme; Teva This study was financially supported by National Health and Medical Research Council of Australia [project grants 1083539 and 1129189, and fellowships 1140766 and 1080518]. The MSBase Foundation is a not-for-profit organization that receives support from Merck, Biogen, Novartis, Bayer-Schering, Sanofi-Genzyme and Teva. The study was conducted separately and apart from the guidance of the sponsors.

Published
2020

45. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis

Author

Warrender-Sparkes, Matthew, Spelman, Tim, Izquierdo, Guillermo, Trojano, Maria, Lugaresi, Alessandra, Grand'Maison, François, Havrdova, Eva, Horakova, Dana, Boz, Cavit, Oreja-Guevara, Celia, Alroughani, Raed, Iuliano, Gerardo, Duquette, Pierre, Girard, Marc, Terzi, Murat, Hupperts, Raymond, Grammond, Pierre, Petersen, Thor, Fernandez-Bolanos, Ricardo, Fiol, Marcela, Pucci, Eugenio, Lechner-Scott, Jeannette, Verheul, Freek, Cristiano, Edgardo, Van Pesch, Vincent, Petkovska-Boskova, Tatjana, Moore, Fraser, Kister, Ilya, Bergamaschi, Roberto, Saladino, Maria Laura, Slee, Mark, Barnett, Michael, Amato, Maria Pia, Shaw, Cameron, Shuey, Neil, Young, Carolyn, Gray, Orla, Kappos, Ludwig, Butzkueven, Helmut, Kalincik, Tomas, Jokubaitis, Vilija, MSBase study group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Ondokuz Mayıs Üniversitesi, Warrender-Sparkes M, Spelman T, Izquierdo G, Trojano M, Lugaresi A, Grand'Maison F, Havrdova E, Horakova D, Boz C, Oreja-Guevara C, Alroughani R, Iuliano G, Duquette P, Girard M, Terzi M, Hupperts R, Grammond P, Petersen T, Fernandez-Bolaños R, Fiol M, Pucci E, Lechner-Scott J, Verheul F, Cristiano E, Van Pesch V, Petkovska-Boskova T, Moore F, Kister I, Bergamaschi R, Saladino Ml, Slee M, Barnett M, Amato Mp, Shaw C, Shuey N, Young C, Gray O, Kappos L, Butzkueven H, Kalincik T, Jokubaitis V, and Msbase study group.

Subjects
Oncology, Male, Time Factors, Administration, Oral, Kaplan-Meier Estimate, Pharmacology, Persistence (computer science), 0302 clinical medicine, Natalizumab, Risk Factors, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, Drug Substitution, Research Support, Non-U.S. Gov't, Middle Aged, Fingolimod, disease-modifying therapy, Treatment Outcome, Neurology, Cohort, Female, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, MSBase, Medication Adherence, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Fingolimod Hydrochloride, medicine, Journal Article, Humans, Multiple sclerosi, fingolimod, Aged, Proportional Hazards Models, business.industry, medicine.disease, Medication Persistence, Multivariate Analysis, Neurology (clinical), business, 030217 neurology & neurosurgery, medication persistence, Demyelinating Diseases
Abstract

Lugaresi, Alessandra/0000-0003-2902-5589; Horakova, Dana/0000-0003-1915-0036; amato, Maria Pia/0000-0003-3325-3760; Havrdova, Eva Kubala/0000-0002-9543-4359; Slee, Mark/0000-0003-4323-2453; Jokubaitis, Vilija G./0000-0002-3942-4340; Oreja-Guevara, Celia/0000-0002-9221-5716; Petersen, Thor/0000-0001-5633-2600; pucci, eugenio/0000-0001-7606-7330; , Carolyn/0000-0001-6971-8203; van Pesch, Vincent/0000-0003-2885-9004; Butzkueven, Helmut/0000-0003-3940-8727; Trojano, Maria/0000-0002-6329-8946; Young, Carolyn/0000-0003-1745-7720; Kalincik, Tomas/0000-0003-3778-1376; Kister, Ilya/0000-0003-3549-949X WOS: 000372890900008 PubMed: 26199347 Objective: We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). Methods: MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. Results: A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p

Published
2016
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46. Increasing age at disability milestones among MS patients in the MSBase Registry

Author

Ilya, Kister, Eric, Chamot, Gary, Cutter, Tamar E, Bacon, Vilija G, Jokubaitis, Stella E, Hughes, Orla M, Gray, Maria, Trojano, Guillermo, Izquierdo, Francois, Grand'Maison, Pierre, Duquette, Alessandra, Lugaresi, Pierre, Grammond, Cavit, Boz, Raymond, Hupperts, Thor, Petersen, Giorgio, Giuliani, Celia, Oreja-Guevara, Gerardo, Iuliano, Jeannette, Lechner-Scott, Roberto, Bergamaschi, Maria Edite, Rio, Freek, Verheul, Marcela, Fiol, Vincent, Van Pesch, Mark, Slee, Helmut, Butzkueven, Joseph, Herbert, Vetere, Santiago, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs School for Mental Health and Neuroscience, Kister I, Chamot E, Cutter G, Bacon TE, Jokubaitis VG, Hughes SE, Gray OM, Trojano M, Izquierdo G, Grand'maison F, Duquette P, Lugaresi A, Grammond P, Boz C, Hupperts R, Petersen T, Giuliani G, Oreja-Guevara C, Iuliano G, Lechner-Scott J, Bergamaschi R, Rio ME, Verheul F, Fiol M, Van Pesch V, Slee M, Butzkueven H, Herbert J, and MSBase Investigators

Subjects
Gerontology, Adult, Male, medicine.medical_specialty, Aging, Epidemiology, MEDLINE, relapsing-remitting physiopathology, Multiple sclerosis, Population-based registry, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, medicine, Humans, Registries, business.industry, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Clinical neurology, Natural history, Neurology, Relapsing remitting, multiple sclerosi, Female, Neurology (clinical), business, Population-Based Registry
Abstract

OBJECTIVE: To analyze time-trends in age at disability milestones among MS patients who were enrolled into the MSBase International Registry during 1996-2010 period.METHODS: We used linear regression to describe the relationship between mean age at major EDSS benchmarks and calendar time. We then assessed time-trend in age at initial EDSS rating with a three level linear growth model specifying that patients were nested within each of 20 participating countries. The model estimated the average of time-trends in mean age at initial clinical assessment within each country while controlling for patients' EDSS and sex in each country. Analyses were repeated in subsamples of patients diagnosed according to Poser or McDonald criteria.RESULTS: The MSBase Registry contained data on 11,108 MS patients enrolled between 1996 and 2010 who fulfilled our inclusion criteria. During the 1996-2010 period, enrollment age for patients with EDSS 4/4.5 increased by 7.9 years, from 43 to 51 years (pCONCLUSIONS: The more recent MSBase enrollees in each of the mild-to-moderate disability strata were significantly older than earlier enrollees. Possible explanations for this phenomenon are discussed.

Published
2012
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47. Neurologic Outcomes in People With Multiple Sclerosis Treated With Immune Checkpoint Inhibitors for Oncologic Indications.

Author

Quinn CM, Rajarajan P, Gill AJ, Kopinsky H, Wolf AB, de Camargo CS, Lamb J, Bacon TE, Murray JC, Probasco JC, Galetta KM, Kantor D, Coyle P, Bhise V, Alvarez E, Conway SE, Bhattacharyya S, and Kister I

Subjects
Humans, Female, Male, Retrospective Studies, Middle Aged, Aged, Adult, Treatment Outcome, Multiple Sclerosis drug therapy, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Neoplasms drug therapy
Abstract

Background and Objectives: Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease following ICI initiation. People with multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on the safety of ICIs in MS are limited. This study aims to assess the rate of MS activity, as well as neurologic and nonneurologic irAEs in persons with MS treated with ICIs for cancer., Methods: Participating sites were invited to this retrospective observational study through the Medical Partnership 4 MS+ listserv. Seven large academic centers participated in the study, each conducting a systematic search of their electronic medical record system for patients with MS and history of ICI treatment. The participating neurologist reviewed each chart individually to ensure the inclusion criteria were met. Demographics and data on MS and cancer history, treatments, and outcomes were abstracted from patient charts using a structured instrument., Results: We identified 66 people with MS (median age 66 years, 73% female, 68% not on disease-modifying therapy for MS) who were treated with ICIs for lung cancer (35%), melanoma (21%), or another oncologic indication. During post-ICI follow-up (median: 11.7 months, range 0.2-106.3 months), 2 patients (3%) had relapse or MRI activity, 3 (5%) had neurologic irAEs, and 21 (32%) had nonneurologic irAEs. At the last follow-up, 25 (38%) participants had partial or complete remission of their cancer, while 35 (53%) were deceased., Discussion: In this multi-institutional systematic retrospective study of predominantly older patients with MS, most of whom were not on disease-modifying therapy, MS activity and neurologic irAEs following ICI treatment were rare. These data suggest that preexisting MS should not preclude the use of ICIs for cancer in older patients, but the results may not be generalizable to younger patients with active MS. Prospective studies of ICI safety that enroll younger patients with MS are needed.

Published
2024
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48. Aquaporin-4 Immunoglobulin G-seropositive Neuromyelitis Optica Spectrum Disorder MRI Characteristics: Data Analysis from the International Real-World PAMRINO Study Cohort.

Author

Chien C, Cruz E Silva V, Geiter E, Meier D, Zimmermann H, Bichuetti DB, Idagawa MI, Altintas A, Tanriverdi U, Siritho S, Pandit L, Dcunha A, Sá MJ, Figueiredo R, Qian P, Tongco C, Lotan I, Khasminsky V, Hellmann MA, Stiebel-Kalish H, Rotstein DL, Waxman L, Ontaneda D, Nakamura K, Abboud H, Subei MO, Mao-Draayer Y, Havla J, Asgari N, Skejø PB, Kister I, Ringelstein M, Broadley S, Arnett S, Marron B, Jolley AM, Wunderlich M, Green S, Cook LJ, Yeaman MR, Smith TJ, Brandt AU, Wuerfel J, and Paul F

Subjects
Humans, Female, Male, Adult, Retrospective Studies, Middle Aged, Cross-Sectional Studies, Aged, Young Adult, Adolescent, Cohort Studies, Neuromyelitis Optica diagnostic imaging, Neuromyelitis Optica immunology, Magnetic Resonance Imaging methods, Aquaporin 4 immunology, Immunoglobulin G blood
Abstract

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD ( n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data ( n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI ( n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Published
2024
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49. Longitudinal study of immunity to SARS-CoV2 in ocrelizumab-treated MS patients up to 2 years after COVID-19 vaccination.

Author

Kister I, Curtin R, Piquet AL, Borko T, Pei J, Banbury BL, Bacon TE, Kim A, Tuen M, Velmurugu Y, Nyovanie S, Selva S, Samanovic MI, Mulligan MJ, Patskovsky Y, Priest J, Cabatingan M, Winger RC, Krogsgaard M, and Silverman GJ

Subjects
Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Antibodies, Viral blood, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Immunity, Cellular drug effects, Vaccination, Immunity, Humoral drug effects, Immunity, Humoral immunology, BNT162 Vaccine administration & dosage, BNT162 Vaccine immunology, COVID-19 immunology, COVID-19 prevention & control, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, SARS-CoV-2 immunology, Multiple Sclerosis immunology, Multiple Sclerosis drug therapy
Abstract

Objectives: (1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity., Methods: Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed-effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses., Results: The primary vaccination induced an 11- to 208-fold increase in binding and neutralizing antibody levels and a 3- to 4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3- to 5-fold increase in binding antibodies and 4- to 5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity., Interpretation: Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2024
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50. Diagnostic Utility of MOG Antibody Testing in Cerebrospinal Fluid.

Author

Redenbaugh V, Fryer JP, Cacciaguerra L, Chen JJ, Greenwood TM, Gilligan M, Thakolwiboon S, Majed M, Chia NH, McKeon A, Mills JR, Lopez Chiriboga AS, Tillema JM, Yang B, Abdulrahman Y, Guo K, Vorasoot N, Valencia Sanchez C, Tajfirouz DA, Toledano M, Zekeridou A, Dubey D, Gombolay GY, Caparó-Zamalloa C, Kister I, Pittock SJ, and Flanagan EP

Subjects
Humans, Retrospective Studies, Female, Male, Adult, Middle Aged, Sensitivity and Specificity, Aged, Adolescent, Young Adult, Child, Myelin-Oligodendrocyte Glycoprotein immunology, Autoantibodies cerebrospinal fluid, Autoantibodies blood, Immunoglobulin G cerebrospinal fluid, Immunoglobulin G blood
Abstract

Objective: The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing., Methods: We retrospectively identified patients for CSF MOG-IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG-IgG for testing including: controls, 282; serum MOG-IgG positive MOG antibody-associated disease (MOGAD), 74; serum MOG-IgG negative high-risk phenotypes, 73; serum false positive MOG-IgG with alternative diagnoses, 18. A live cell-based assay assessed CSF MOG-IgG positivity (IgG-binding-index [IBI], ≥2.5) using multiple anti-human secondary antibodies and end-titers were calculated if sufficient sample volume. Correlation of CSF MOG-IgG IBI and titer was assessed., Results: The pan-IgG Fc-specific secondary was optimal, yielding CSF MOG-IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG-IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG-IgG positive MOGAD patients; and 9/73 (12%) serum MOG-IgG negative patients with high-risk phenotypes. Serum negative but CSF positive MOG-IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG-IgG low-positives revealed CSF MOG-IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG-IgG (3/15[20%]) (p = 0.01). CSF MOG-IgG IBI and CSF MOG-IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001)., Interpretation: CSF MOG-IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG-IgG, and those with low positive serum MOG-IgG results and diagnostic uncertainty. These findings support a role for CSF MOG-IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34-45., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2024
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