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4. MRI-based prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis using SVM and lesion geometry

Author

Bendfeldt, Kerstin, Taschler, Bernd, Gaetano, Laura, Madoerin, Philip, Kuster, Pascal, Mueller-Lenke, Nicole, Amann, Michael, Vrenken, Hugo, Wottschel, Viktor, Barkhof, Frederik, Borgwardt, Stefan, Klöppel, Stefan, Wicklein, Eva-Maria, Kappos, Ludwig, Edan, Gilles, Freedman, Mark S., Montalbán, Xavier, Hartung, Hans-Peter, Pohl, Christoph, Sandbrink, Rupert, Sprenger, Till, Radue, Ernst-Wilhelm, Wuerfel, Jens, and Nichols, Thomas E.

Published
2019
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5. Serum metabolic profile in early multiple sclerosis as predictor of long-term disease progression in BENEFIT (P5-3.013)

Author

Cortese, Marianna, primary, Peng, Xiaojing, additional, Bjornevik, Kjetil, additional, Clish, Clary B., additional, Edan, Gilles, additional, Freedman, Mark, additional, Hartung, Hans-Peter, additional, Montalban, Xavier, additional, Sandbrink, Rupert, additional, Radue, Ernst-Wilhelm, additional, Barkhof, Frederik, additional, Wicklein, Eva-Maria, additional, Kappos, Ludwig, additional, Munger, Kassandra, additional, and Ascherio, Alberto, additional

Published
2023
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6. Bile Acids Metabolites as Predictors of long-term Multiple Sclerosis Progression (S5.004)

Author

Cortese, Marianna, primary, Bjornevik, Kjetil, additional, Clish, Clary B., additional, Edan, Gilles, additional, Freedman, Mark, additional, Hartung, Hans-Peter, additional, Montalban, Xavier, additional, Sandbrink, Rupert, additional, Radue, Ernst-Wilhelm, additional, Barkhof, Frederik, additional, Wicklein, Eva-Maria, additional, Kappos, Ludwig, additional, Munger, Kassandra, additional, and Ascherio, Alberto, additional

Published
2022
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7. A Prospective Study of Serum Levels of Polyunsaturated Fatty Acids and Effects on Multiple Sclerosis Disease Activity and Progression (S40.006)

Author

Munger, Kassandra, primary, Bjornevik, Kjetil, additional, Cortese, Marianna, additional, Edan, Gilles, additional, Freedman, Mark, additional, Hartung, Hans-Peter, additional, Montalban, Xavier, additional, Sandbrink, Rupert, additional, Radue, Ernst-Wilhelm, additional, Barkhof, Frederik, additional, Wicklein, Eva-Maria, additional, Kappos, Ludwig, additional, and Ascherio, Alberto, additional

Published
2022
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8. Body mass index as a predictor of MS activity and progression among participants in BENEFIT

Author

Manuel Escobar, Juan, primary, Cortese, Marianna, additional, Edan, Gilles, additional, Freedman, Mark S, additional, Hartung, Hans-Peter, additional, Montalbán, Xavier, additional, Sandbrink, Rupert, additional, Radü, E-W, additional, Barkhof, Frederik, additional, Wicklein, Eva-Maria, additional, Kappos, Ludwig, additional, Ascherio, Alberto, additional, and Munger, Kassandra L, additional

Published
2022
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10. Real-World Assessment of Interferon-β-1b and Interferon-β-1a Adherence Before and After the Introduction of the BETACONNECT® Autoinjector: A Retrospective Cohort Study.

Author

Butler, Oisín, Heeg, Simone, Holl, Katsiaryna, Frenz, Ann-Kathrin, Wicklein, Eva-Maria, Rametta, Mark, and Yeo, Sandy

Subjects
INTERFERON beta 1b, COHORT analysis, ADULTS, INTERFERON beta-1a, DEMOGRAPHIC characteristics, RETROSPECTIVE studies, INTERFERONS
Abstract

Background: Both interferon beta-1b (IFN-β-1b) and interferon beta-1a (IFN-β-1a) are immunomodulators that require regular subcutaneous self-administration by patients with multiple sclerosis (MS). However, no electronic autoinjector is available for IFN-β-1a in the US. Objective: This retrospective cohort study investigated adherence to two subcutaneous disease-modifying therapies, IFN-β-1b and IFN-β-1a, during two periods (before and after the introduction of the BETACONNECT® autoinjector for IFN-β-1b). Patients and Methods: Data were evaluated from the MarketScan database for adults in the US with an MS diagnosis and a medical claim for subcutaneous IFN-β-1b or IFN-β-1a, either before (October 2013–September 2015) or after the introduction of BETACONNECT (October 2016–September 2018). Patient populations were propensity-score matched by demographic and clinical characteristics. Persistence was recorded, and adherence was evaluated by medication possession ratio (MPR). Results: The study included 196 IFN-β-1b and 365 IFN-β-1a people with MS (PwMS) (pre-BETACONNECT period), and 126 IFN-β-1b and 223 IFN-β-1a PwMS (post-BETACONNECT period). In the pre-BETACONNECT period, the proportion with at least 80% MPR was higher for IFN-β-1a (90%) than for IFN-β-1b (83%), but in the post-BETACONNECT period the proportion with ≥ 80% MPR was higher for IFN-β-1b (92%) than for IFN-β-1a (86%). In the pre-BETACONNECT period, median persistence (in days) was higher for IFN-β-1a (199) than for IFN-β-1b (152), while in post-BETACONNECT period persistence was higher for IFN-β-1b (327) than for IFN-β-1a (229). Conclusions: Following the introduction of BETACONNECT, this exploratory study suggested that PwMS taking IFN-β-1b were more adherent compared with those taking IFN-β-1a, with higher persistence, and more than 90% reached 80% MPR, a threshold commonly used to define good adherence. [ABSTRACT FROM AUTHOR]

Published
2021
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12. Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden

Author

Hakkarainen, Katja Marja, primary, Juuti, Rosa, additional, Burkill, Sarah, additional, Geissbühler, Yvonne, additional, Sabidó, Meritxell, additional, Popescu, Catrinel, additional, Suzart-Woischnik, Kiliana, additional, Hillert, Jan, additional, Artama, Miia, additional, Verkkoniemi-Ahola, Auli, additional, Myhr, Kjell-Morten, additional, Mehtälä, Juha, additional, Bahmanyar, Shahram, additional, Montgomery, Scott, additional, Korhonen, Pasi, additional, Adamo, Alessandra, additional, Wicklein, Eva-Maria, additional, Akbaba, Metin, additional, Borghesi, Gustavo, additional, Köfüncü, Evra, additional, Everage, Nicholas, additional, Pandhi, Avni, additional, Naylor, Maria, additional, Ly, Anh, additional, Jack, Dominic, additional, Todorovic, Milorad, additional, Issard, Delphine, additional, Macklin, Alexandra, additional, Primatesta, Paola, additional, Weitzman, Richard, additional, Klement, Riho, additional, Vehkala, Minna, additional, Vattulainen, Pia, additional, Korjagina, Marta, additional, and Gyllensten, Hanna, additional

Published
2020
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13. Vitamin D and Tobacco Use and Long-Term Clinical and MRI Outcomes among CIS patients: 11-year Follow-up of BENEFIT. (P5.2-003)

Author

Martinez-Lapiscina, Elena, primary, Munger, Kassandra, additional, Cortese, Marianna, additional, Barkhof, Frederik, additional, Edan, Gilles, additional, Freedman, Mark, additional, Hartung, Hans-Peter, additional, Montalban, Xavier, additional, Kappos, Ludwig, additional, Foley, Frederick, additional, Penner, Iris Katharina, additional, Hemmer, Bernhard, additional, Fox, Edward, additional, Schippling, Sven, additional, Wicklein, Eva-Maria, additional, and Ascherio, Alberto, additional

Published
2019
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17. Sodium intake and multiple sclerosis activity and progression in BENEFIT

Author

Fitzgerald, Kathryn C., Munger, Kassandra L., Hartung, Hans peter, Freedman, Mark S., Montalbã¡n, Xavier, Edan, Gilles, Wicklein, Eva maria, Radue, Ernst wilhelm, Kappos, Ludwig, Pohl, Christoph, Ascherio, Alberto, Strasser fuchs, S., Berger, T., Vass, K., Sindic, C., Dubois, B., Dive, D., Debruyne, J., Metz, L., Rice, G., Duquette, P., Lapierre, Y., Freedman, M., Traboulsee, A., O'Connor, P., Å touraä, P., Talab, R., Zapletalova, O., Kovaå™ova, I., Medova, E., Fiedler, J., Frederiksen, J., Brochet, B., Moreau, T., Vermersch, P., Pelletier, J., Edan, G., Clanet, M., Clavelou, P., Lebrun frenay, C., Gout, O., Kallela, M., Pirttila, T., Ruutiainen, J., Koivisto, K., Reunanen, M., Elovaara, I., Villringer, A., Altenkirch, H., Wessel, K., Hartung, H. . P., Steinke, W., Kã¶lmel, H., Oschmann, P., Diem, R., Dressel, A., Hoffmann, F., Baum, K., Jung, S., Petereit, H., Reske, D., Sailer, M., Kohler, J., Sommer, N., Hohlfeld, R., Henn, K. . H., Tumani, H., Gold, R., Rieckmann, P., Komoly, R., Gacs, G., Jakab, G., Csiba, L., Vecsei, L., Miller, A., Karussis, D., Chapman, J., Ghezzi, A., Gallo, P., Cosi, V., Durelli, L., Anten, B., Visser, L., Myhr, K. . M., Szczudlik, A., Selmaj, K., Stelmasiak, Z., Podemski, R., Maciejek, Z., Cunha, L., Sega jazbec, S., Montalban, X., Arbizu, T., Saiz, A., Barcena, J., Arroyo, R., Fernandez, O., Izquierdo, G., Casanova, B., Lycke, J., Kappos, L., Mattle, H., Beer, K., Coleman, R., Chataway, J., Riordan, J. O., Howell, S., COMI, GIANCARLO, Fitzgerald, Kathryn C., Munger, Kassandra L., Hartung, Hans peter, Freedman, Mark S., Montalbã¡n, Xavier, Edan, Gille, Wicklein, Eva maria, Radue, Ernst wilhelm, Kappos, Ludwig, Pohl, Christoph, Ascherio, Alberto, Strasser fuchs, S., Berger, T., Vass, K., Sindic, C., Dubois, B., Dive, D., Debruyne, J., Metz, L., Rice, G., Duquette, P., Lapierre, Y., Freedman, M., Traboulsee, A., O'Connor, P., Å touraä , P., Talab, R., Zapletalova, O., Kovaå ova, I., Medova, E., Fiedler, J., Frederiksen, J., Brochet, B., Moreau, T., Vermersch, P., Pelletier, J., Edan, G., Clanet, M., Clavelou, P., Lebrun frenay, C., Gout, O., Kallela, M., Pirttila, T., Ruutiainen, J., Koivisto, K., Reunanen, M., Elovaara, I., Villringer, A., Altenkirch, H., Wessel, K., Hartung, H. . P., Steinke, W., Kã¶lmel, H., Oschmann, P., Diem, R., Dressel, A., Hoffmann, F., Baum, K., Jung, S., Petereit, H., Reske, D., Sailer, M., Kohler, J., Sommer, N., Hohlfeld, R., Henn, K. . H., Tumani, H., Gold, R., Rieckmann, P., Komoly, R., Gacs, G., Jakab, G., Csiba, L., Vecsei, L., Miller, A., Karussis, D., Chapman, J., Ghezzi, A., Comi, Giancarlo, Gallo, P., Cosi, V., Durelli, L., Anten, B., Visser, L., Myhr, K. . M., Szczudlik, A., Selmaj, K., Stelmasiak, Z., Podemski, R., Maciejek, Z., Cunha, L., Sega jazbec, S., Montalban, X., Arbizu, T., Saiz, A., Barcena, J., Arroyo, R., Fernandez, O., Izquierdo, G., Casanova, B., Lycke, J., Kappos, L., Mattle, H., Beer, K., Coleman, R., Chataway, J., Riordan, J. O., and Howell, S.

Subjects
Adult, Male, Brain, Demyelinating Disease, Neuroimaging, Sodium, Dietary, Magnetic Resonance Imaging, Disability Evaluation, Young Adult, Neurology, Multiple Sclerosi, Disease Progression, Female, Neurology (clinical), Human, Interferon beta-1b
Abstract

Objective: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. Methods: BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13–16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes. Results: Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67–1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97–1.13; relative change in T2 lesion volume: −0.11, 95% CI = −0.25 to 0.04; change in EDSS: −0.01, 95% CI = −0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56–1.07). Results were similar in categorical analyses using quintiles. Interpretation: Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20–29.

Published
2017
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18. Real-World Assessment of Interferon-β-1b and Interferon-β-1a Adherence Before and After the Introduction of the BETACONNECT®Autoinjector: A Retrospective Cohort Study

Author

Butler, Oisín, Heeg, Simone, Holl, Katsiaryna, Frenz, Ann-Kathrin, Wicklein, Eva-Maria, Rametta, Mark, and Yeo, Sandy

Abstract

Background: Both interferon beta-1b (IFN-β-1b) and interferon beta-1a (IFN-β-1a) are immunomodulators that require regular subcutaneous self-administration by patients with multiple sclerosis (MS). However, no electronic autoinjector is available for IFN-β-1a in the US. Objective: This retrospective cohort study investigated adherence to two subcutaneous disease-modifying therapies, IFN-β-1b and IFN-β-1a, during two periods (before and after the introduction of the BETACONNECT®autoinjector for IFN-β-1b). Patients and Methods: Data were evaluated from the MarketScan database for adults in the US with an MS diagnosis and a medical claim for subcutaneous IFN-β-1b or IFN-β-1a, either before (October 2013–September 2015) or after the introduction of BETACONNECT (October 2016–September 2018). Patient populations were propensity-score matched by demographic and clinical characteristics. Persistence was recorded, and adherence was evaluated by medication possession ratio (MPR). Results: The study included 196 IFN-β-1b and 365 IFN-β-1a people with MS (PwMS) (pre-BETACONNECT period), and 126 IFN-β-1b and 223 IFN-β-1a PwMS (post-BETACONNECT period). In the pre-BETACONNECT period, the proportion with at least 80% MPR was higher for IFN-β-1a (90%) than for IFN-β-1b (83%), but in the post-BETACONNECT period the proportion with ≥ 80% MPR was higher for IFN-β-1b (92%) than for IFN-β-1a (86%). In the pre-BETACONNECT period, median persistence (in days) was higher for IFN-β-1a (199) than for IFN-β-1b (152), while in post-BETACONNECT period persistence was higher for IFN-β-1b (327) than for IFN-β-1a (229). Conclusions: Following the introduction of BETACONNECT, this exploratory study suggested that PwMS taking IFN-β-1b were more adherent compared with those taking IFN-β-1a, with higher persistence, and more than 90% reached 80% MPR, a threshold commonly used to define good adherence.

Published
2021
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19. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry.

Author

Hellwig, Kerstin, Geissbuehler, Yvonne, Sabidó, Meritxell, Popescu, Catrinel, Adamo, Alessandra, Klinger, Joachim, Ornoy, Asher, Huppke, Peter, the European Interferon-beta Pregnancy Study Group, Akbaba, Metin, Borghesi, Gustavo, Bugge, Joerg-Peter, Detering, Elke, Köfüncü, Evra, Luenzmann, Claudia, Mueller, Bettina, Olivar, Axel, Suzart-Woischnik, Kiliana, Wicklein, Eva-Maria, and Beynon, Vanessa

Subjects
MULTIPLE sclerosis, MISCARRIAGE, PREGNANCY, PREGNANCY outcomes, PREGNANT women, MEDICAL personnel, ECTOPIC pregnancy
Abstract

Background: Family planning is an important consideration for women with multiple sclerosis (MS), who are often diagnosed during their reproductive years. Currently, limited data are available on pregnancy outcomes in patients exposed to interferon-beta (IFN-beta) before or during pregnancy. Here, we present the cumulative pregnancy exposure data and prevalence of pregnancy and infant outcomes in IFN-beta-exposed pregnant women with MS from the European IFN-beta Pregnancy Registry. Methods: Using spontaneous and solicited reports, the registry collected data from 26 countries of the European Economic Area, consisting of information on women with MS identifying themselves to one of the Marketing Authorisation Holders (Bayer, Biogen, Merck KGaA, and Novartis) or healthcare professionals as pregnant and exposed to IFN-beta during pregnancy or within 1 month before conception. The outcomes collected by the registry included ectopic pregnancies, spontaneous abortions, elective terminations, live, and stillbirths with or without congenital anomalies. The prevalence of pregnancy outcomes was put in context with those reported in the general population. Results: Between 2009 and 2017, the registry collected 948 pregnancy reports with a known pregnancy outcome. Overall, 82.0% (777/948) of pregnancies resulted in live birth without congenital anomaly. When comparing IFN-beta-exposed pregnancies with the general population, the prevalence of spontaneous abortions (10.7% vs. 10–21%) and congenital anomalies in live births (2.1% vs. 2.1–4.1%) were found to be within reported ranges. Conclusions: The data gathered from these pregnancy cases suggest no evidence that IFN-beta exposure before conception and/or during pregnancy adversely increases the rate of congenital anomalies or spontaneous abortions. [ABSTRACT FROM AUTHOR]

Published
2020
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20. Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.

Author

Cortese, Marianna, Munger, Kassandra L., Martinez-Lapiscina, Elena H., Barro, Christian, Edan, Gilles, Freedman, Mark S., Hartung, Hans-Peter, Montalban, Xavier, Foley, Frederick W., Penner, Iris Katharina, Hemmer, Bernhard, Fox, Edward J., Schippling, Sven, Wicklein, Eva-Maria, Kappos, Ludwig, Kuhle, Jens, Ascherio, Alberto, Martínez-Lapiscina, Elena H, Montalbán, Xavier, and BENEFIT Study Group

Published
2020
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21. MRI-based prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis using SVM and lesion geometry

Author

Bendfeldt, Kerstin, primary, Taschler, Bernd, additional, Gaetano, Laura, additional, Madoerin, Philip, additional, Kuster, Pascal, additional, Mueller-Lenke, Nicole, additional, Amann, Michael, additional, Vrenken, Hugo, additional, Wottschel, Viktor, additional, Barkhof, Frederik, additional, Borgwardt, Stefan, additional, Klöppel, Stefan, additional, Wicklein, Eva-Maria, additional, Kappos, Ludwig, additional, Edan, Gilles, additional, Freedman, Mark S., additional, Montalbán, Xavier, additional, Hartung, Hans-Peter, additional, Pohl, Christoph, additional, Sandbrink, Rupert, additional, Sprenger, Till, additional, Radue, Ernst-Wilhelm, additional, Wuerfel, Jens, additional, and Nichols, Thomas E., additional

Published
2018
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22. Long-term safety of interferon beta-1b (IFNB-1b) treatment in early multiple sclerosis ( MS): The 11-year follow-up of BENEFIT (BENEFIT-11)

Author

Freedman, Mark S., Kappos, Ludwig, Edan, Gilles, Montalban, Xavier, Hartung, Hans-Peter, Hemmer, Bernhard, Fox, Edward, Barkhof, Frederik, Schippling, Sven, Schulze, Andrea, Pleimes, Dirk, Pohl, Christoph, Sandbrink, Rupert, Suarez, Gustavo A., Wicklein, Eva-Maria, Department of Biomedicine [Basel], University Hospital Basel [Basel], Centre d'Investigation Clinique [Rennes] (CIC), 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), CHU Pontchaillou [Rennes], Vall d'Hebron University Hospital [Barcelona], Department of neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Central Texas Neurology Consultants [Round Rock], VU University Medical Center [Amsterdam], University hospital of Zurich [Zurich], PAREXEL International [Berlin], Myelo Therapeutics [Berlin], Bayer Pharma AG [Berlin], Rheinische Friedrich-Wilhelms-Universität Bonn, Jonchère, Laurent, and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

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

International audience; Meeting Abstract: P028 - ACTRIMS Forum, New Orleans, LA, feb 2016

Published
2016

23. Long-term Impact of Early MS Treatment with Interferon Beta-1b (IFNB-1b): Clinical, MRI, Employment, and Patient-Reported Outcomes (PROs) at the 11-Year Follow-up of BENEFIT (BENEFIT 11) (P7.012)

Author

Edan, Gilles, Freedman, Mark, Montalban, Xavier, Miller, David, Hartung, Hans, Hemmer, Bernhard, Fox, Edward, Barkhof, Frederik, Schippling, Sven, Schulze, Andrea, Pleimes, Dirk, Pohl, Christoph, Sandbrink, Rupert, Suarez, Gustavo, Wicklein, Eva-Maria, Kappos, Ludwig, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Ottawa Hospital Research Institute [Ottawa] (OHRI), Vall d'Hebron University Hospital [Barcelona], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Central Texas Neurology Consultants [Round Rock], VU University Medical Center [Amsterdam], University hospital of Zurich [Zurich], PAREXEL International [Berlin], Myelo Therapeutics [Berlin], Bayer Pharma AG [Berlin], Rheinische Friedrich-Wilhelms-Universität Bonn, Bayer HealthCare Pharmaceuticals Inc [Whippany], Department of Biomedicine [Basel], University Hospital Basel [Basel], 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 Jonchère, Laurent

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

International audience; OBJECTIVE:To study long-term outcomes in patients treated with IFNB-1b after clinically isolated syndrome (CIS). BACKGROUND:In BENEFIT, patients with CIS were randomized to IFNB-1b or placebo (PL) treatment. After the second clinical event or after 2 years, all patients were treated with IFNB-1b. Mean delay of IFNB-1b in PL was 1.33 years. Comprehensive clinical, MRI, and PROs at 11 years post-randomization are reported. DESIGN/METHODS:All originally randomized patients were asked to undergo clinical, MRI, laboratory, and PRO assessments 11 years after randomization. RESULTS:281 patients were identified (60[percnt] of originally randomized, 72.6[percnt] of eligible patients at participating sites); 278 enrolled. Baseline characteristics were similar to the original BENEFIT population. At Year 11, patients randomized to IFNB-1b still had lower overall annualized relapse rate (p=0.0018) and longer time to first relapse (p=0.0005) and clinically definite MS (p=0.0012). Median EDSS score was 2.0 (change from baseline 0.5) in both groups. PASAT scores remained high (overall median 56 [IQR 10]). Of the 81.3[percnt] working at CIS start, 73.4[percnt] were still employed (64.4[percnt] fulltime). 12.2[percnt] retired early or were on long-term disability (2.9[percnt] at baseline). 64.0[percnt] did not report any sick leave during the past 12 months. Health-related quality of life remained stable (median [IQR] change from baseline EQ-5D: 0.000 [0.209], FAMS TOI: -7.54 [27.17]. Median (IQR) fatigue (FSMC) score: 45.00 (40.00), 46[percnt] of patients without fatigue (cut-off score\textless43), median (IQR) depression (CES-D) score: 9.00 (15.00). MRI findings were similar across groups: 86.4[percnt] had no gadolinium-enhancing lesions; median (IQR) number of new T2 lesions since 5-year MRI: 2.0 (6.0), T2 volume: 1760.0mm³ (3963.0mm³), cortical lesions: 2.0 (5.0), brain volume 1519.0cm³ (152.0mm³), mean cortical thickness 2.64mm³ (0.56mm³). CONCLUSIONS:Results from BENEFIT11 support a long-term impact of early treatment with IFNB-1b on clinical measures, including cognition and fatigue, and health economic and MRI outcomes. Study Supported by:Bayer HealthCare Pharmaceuticals Disclosure: Dr. Edan has received personal compensation for activities with LFB, Biogenidec, speaking from Serono, Inc., Sanofi, Teva, and Bayer Pharmaceuticals Corporation as a consultant and/or scientific advisory board member. Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi-Aventis, and Teva Canada Innovation. Dr. Montalban has received personal compensation for activities with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline Inc., Novartis, Merck & Co. Inc., Chugai, and Mitsubishi Pharma. Dr. Miller has received personal compensation in an editorial capac Dr. Hartung has holds stock and/or stock options from Opexa Therapeutics. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer Schering, Merck Serono, Biogen Idec, GlaxoSmithKline, Chugai Pharmaceutical, Micromet, and Genzyme as a scientific advisory board member. Dr. Fox has received personal compensation for activities Acorda Therapeutics, Bayer Pharmaceuticals Corporation, Biogen Idec, Eli Lilly & Company, EMD Serono, Genzyme Corporation, GlaxoSmithKline, and Novartis. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Sanofi, Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, Synthon BV, and Janssen Research as a consultant. Dr. Schippling has received personal compensation for activities with Novartis. Dr. Schippling has received research support from Bayer Schering and Biogen Idec. Dr. Schulze has received personal compensation for activities with PAREXEL International as an employee. Dr. Pleimes has received personal compensation for activities with Myelo Therapeutics GmbH as an employee, and with Bayer Pharmaceuticals Corp. as an employee and consultant. Dr. Pohl has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Pohl owns stock and/or stock options in Bayer Pharmaceuticals Corporation. Dr. Sandbrink has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Sandbrink holds stock and/or stock options in Bayer Pharmaceuticals Corporation. Dr. Suarez has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Wicklein has received personal compensation for activities with Bayer Pharmaceuticals Corporation as an employee. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals

Published
2015

24. Predictive validity of NEDA in the 16- and 21-year follow-up from the pivotal trial of interferon beta-1b.

Author

Goodin, Douglas S, Reder, Anthony T, Traboulsee, Anthony L, Li, David KB, Langdon, Dawn, Cutter, Gary, Cook, Stuart, O'Donnell, Timothy, Kremenchutzky, Marcelo, Oger, Joel, Koelbach, Ralf, Pohl, Christoph, and Wicklein, Eva-Maria

Subjects
PREDICTIVE validity, INTERFERONS, MAGNETIC resonance imaging, MULTIPLE sclerosis
Abstract

Background: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). Objective: To examine the predictive validity of different NEDA definitions. Methods: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. Results: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs (p = 0.0029), as did baseline EDSS (p < 0.0001), baseline T2-BOD (p < 0.0001), and change in T2-BOD (p = 0.0033). IFNB-1b treatment (p = 0.0251), relapse rate in the 2 years before study start (p = 0.0260), T2-BOD at baseline (p = 0.0014), and change in T2-BOD (p = 0.0129) predicted survival at 21 years. Conclusion: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity. [ABSTRACT FROM AUTHOR]

Published
2019
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25. Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials.

Author

Buck, Dorothea, Andlauer, Till F. M., Igl, Wilmar, Wicklein, Eva-Maria, Mühlau, Mark, Weber, Frank, Köchert, Karl, Pohl, Christoph, Arnason, Barry, Comi, Giancarlo, Cook, Stuart, Filippi, Massimo, Hartung, Hans-Peter, Jeffery, Douglas, Kappos, Ludwig, Barkhof, Frederik, Edan, Gilles, Freedman, Mark S., Montalbán, Xavier, and Müller-Myhsok, Bertram

Subjects
ONTOGENY, INTERFERONS, MULTIPLE sclerosis treatment, IMMUNOGLOBULINS, ALLELES, GENETIC markers
Abstract

Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies. [ABSTRACT FROM AUTHOR]

Published
2019
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26. Sodium intake and multiple sclerosis activity and progression in BENEFIT

Author

Fitzgerald, Kathryn C, Munger, Kassandra L, Hartung, Hans-Peter, Freedman, Mark S, Montalbán, Xavier, Edan, Gilles, Wicklein, Eva-Maria, Radue, Ernst-Wilhelm, Kappos, Ludwig, Pohl, Christoph, Ascherio, Alberto, Strasser-Fuchs, S, Berger, T, Vass, K, Fredriksen, J, Kesselring, J, Petkau, A J, Toyka, K V, Fitzgerald, Kathryn C, Munger, Kassandra L, Hartung, Hans-Peter, Freedman, Mark S, Montalbán, Xavier, Edan, Gilles, Wicklein, Eva-Maria, Radue, Ernst-Wilhelm, Kappos, Ludwig, Pohl, Christoph, Ascherio, Alberto, Strasser-Fuchs, S, Berger, T, Vass, K, Fredriksen, J, Kesselring, J, Petkau, A J, and Toyka, K V

Abstract

OBJECTIVE: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability.METHODS: BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes.RESULTS: Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles.INTERPRETATION: Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.

Published
2017

27. Baseline Predictors of Disease Activity in Patients with CIS Treated with Interferon beta-1b in the BENEFIT 11 Trial (P2.121)

Author

Freedman, Mark, primary, Kappos, Ludwig, additional, Edan, Gilles, additional, Montalban, Xavier, additional, Hartung, Hans, additional, Hemmer, Bernhard, additional, Fox, Edward, additional, Barkhof, Frederik, additional, Schippling, Sven, additional, Koelbach, Ralf, additional, Pleimes, Dirk, additional, Suarez, Gustavo, additional, and Wicklein, Eva-Maria, additional

Published
2016
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30. Real-World Evidence Assessment of Betaseron (interferon beta-1b) Adherence Following the Introduction of the BETACONNECT Autoinjector.

Author

Butler, Oisin, Werner, Simone, Holl, Katsiaryna, Frenz, Ann-Kathrin, Wicklein, Eva-Maria, Yeo, Sandy, and Rametta, Mark

Subjects
THERAPEUTIC use of interferons, CONFERENCES & conventions, PATIENT compliance, SELF medication
Abstract

Background: Maintaining adherence to disease-modifying therapies (DMTs) is challenging for chronic conditions such as multiple sclerosis (MS), and poor adherence in MS has been associated with increased risk of disease activity and higher resource utilization. For DMTs requiring parenteral self-administration, such as interferons, autoinjector devices may help patients overcome injection-related factors interfering with treatment adherence. The BETACONNECT device is an electronic autoinjector for the injection of interferon beta-1b (Betaseron), a DMT used in relapsing-remitting MS (RRMS). Objectives: This retrospective analysis of a US claims database evaluated adherence, as indexed by medication possession ratio (MPR) and persistence, to 2 subcutaneous DMTs, Rebif (interferon beta-1a) and Betaseron (interferon beta-1b), during the period prior to and following the introduction of the BETACONNECT autoinjector for Betaseron in patients with MS. Methods: Data from MarketScan, a US claims database, for patients with a medical claim for Rebif or Betaseron either prior to the introduction of BETACONNECT (October 2013-September 2015) or post approval and uptake of BETACONNECT (October 2016-September 2018), were evaluated. Patients aged ≥18 years with ≥1 confirmed MS diagnosis in the 12-month period prior to the first relevant DMT prescription within the defined time periods were included in this analysis. Four cohorts were defined: incident Rebif or Betaseron users over the 24-month period prior to the introduction of BETACONNECT or over the 24-month period following the introduction and uptake of BETACONNECT. Within each time period, patient populations were propensity score matched on demographic and clinical characteristics. MPR and persistence to both DMTs are described for the period prior to and following the introduction of BETACONNECT. Results: MPR: In the pre-BETACONNECT period, the proportion of users with ≥80% MPR was higher for Rebif (90%, 95% CI 87%-93%) than Betaseron (83%, 95% CI 76%-88%), while in the post-BETACONNECT period, the proportion of users with ≥80% MPR was higher for Betaseron (92%, 95% CI 85%-95%) than Rebif (86%, 95% CI 81%-91%). Persistence: In the pre-BETACONNECT period, median persistence in days was higher for Rebif (199, 95% CI 167-235) than for Betaseron (152, 95% CI 105-231), while in the post-BETACONNECT period, persistence was higher for Betaseron (327, 95% CI 244-440) than for Rebif (229, 95% CI 184-304). Conclusions: Following the introduction of BETACONNECT, Betaseron users were more adherent, with improved persistence and with >90% of users meeting 80% MPR, a threshold commonly used to define good adherence. [ABSTRACT FROM AUTHOR]

Published
2020

31. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial

Author

Kappos, Ludwig, Edan, Gilles, Freedman, Mark S., Montalbán, Xavier, Hartung, Hans-Peter, Hemmer, Bernhard, Fox, Edward J., Barkhof, Frederik, Schippling, Sven, Schulze, Andrea, Pleimes, Dirk, Pohl, Christoph, Sandbrink, Rupert, Suarez, Gustavo, Wicklein, Eva-Maria, Csiba, László, Csépány, Tünde, University of Basel (Unibas), 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), Ottawa Hospital Research Institute [Ottawa] (OHRI), Vall d'Hebron University Hospital [Barcelona], 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), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Virginia Tech [Blacksburg], University hospital of Zurich [Zurich], PAREXEL International [Berlin], VU University Medical Center [Amsterdam], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Bayer HealthCare Pharmaceuticals Inc [Whippany], Bayer Pharma AG [Berlin], University of Zurich, Kappos, L, Edan, Gilles, 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), Dubois, Bénédicte, Department of Neurology [Suisse], University Hospital Basel [Basel], 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 Rennes (UNIV-RENNES)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES)-CentraleSupélec-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 Rennes (UNIV-RENNES)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], The Ottawa Hospital, Medical Image Analysis Center (MIAC AG), Department of neurology, Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Munich Cluster of Systems Neurology (SyNery), Department Neurology of the Klinikum rechts der Isar, Technische Universität München [München] (TUM), Myelo Therapeutics [Berlin], Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Radiology and nuclear medicine, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
0301 basic medicine, Male, Cross-sectional study, MESH: Adjuvants, Immunologic, Kaplan-Meier Estimate, Disability Evaluation, 0302 clinical medicine, Recurrence, Medicine, MESH: Double-Blind Method, Young adult, 10. No inequality, MESH: Treatment Outcome, Clinically isolated syndrome, MESH: Disability Evaluation, Orvostudományok, MESH: Follow-Up Studies, 3. Good health, Treatment Outcome, 2728 Neurology (clinical), MESH: Young Adult, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Interferon beta-1b, Adult, medicine.medical_specialty, Randomization, MESH: Demyelinating Diseases, 610 Medicine & health, MESH: Interferon beta-1b, Placebo, Klinikai orvostudományok, Article, Time-to-Treatment, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Adjuvants, Immunologic, Double-Blind Method, Immunologic/administration & dosage* Adult Cross-Sectional Studies Demyelinating Diseases/diagnostic imaging Demyelinating Diseases/drug therapy* Disability Evaluation Double-Blind Method Female Follow-Up Studies Humans Interferon beta-1b/administration & dosage* Kaplan-Meier Estimate Male Recurrence Time-to-Treatment Treatment Outcome Young Adult, Internal medicine, Humans, Adjuvants, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Time-to-Treatment, MESH: Kaplan-Meier Estimate, Expanded Disability Status Scale, MESH: Humans, business.industry, Multiple sclerosis, MESH: Adult, medicine.disease, MESH: Male, Surgery, 10040 Clinic for Neurology, MESH: Recurrence, 030104 developmental biology, Cross-Sectional Studies, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, Demyelinating Diseases, Follow-Up Studies
Abstract

Objective: To assess outcomes for patients treated with interferon beta-1b immediately after clinicallyisolated syndrome (CIS) or after a short delay.Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment)were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayedtreatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients onplacebo could switch to interferon beta-1b or another treatment. Eleven years after randomization,patients were reassessed.Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible atparticipating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk ofCDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 50.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931[253, 3,296]; p50.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p50.0018). Only25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiplesclerosis. Expanded Disability Status Scale scores remained low and stable, with no differencebetween treatment arms (median [Q1,Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better PacedAuditory Serial Addition Task–3 total scores (p 5 0.0070). Employment rates remained high, andhealth resource utilization tended to be low in both groups.MRI metrics did not differ between groups.Conclusions: Although the delay in treatment was relatively short, several clinical outcomesfavored earlier treatment. Along with low rates of disability and disease progression in bothgroups, this supports the value of treatment at CIS., NCT01795872.

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32. Sodium intake and multiple sclerosis activity and progression in BENEFIT

Author

Fitzgerald, Kathryn C, Munger, Kassandra L, Hartung, Hans-Peter, Freedman, Mark S, Montalbán, Xavier, Edan, Gilles, Wicklein, Eva-Maria, Radue, Ernst-Wilhelm, Kappos, Ludwig, Pohl, Christoph, Ascherio, Alberto, and BENEFIT, Study Group

Subjects
10. No inequality, 610 Medicine & health
Abstract

OBJECTIVE To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. METHODS BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes. RESULTS Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. INTERPRETATION Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.

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