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Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab

S. Pfeuffer, L. Rolfes, J. Ingwersen, R. Pul, K. Kleinschnitz, M. Korsen, S. Räuber, T. Ruck, S. Schieferdecker, AG. Willison, O. Aktas, C. Kleinschnitz, HP. Hartung, L. Kappos, SG. Meuth

Pfeuffer, Steffen
Autor Pfeuffer, Steffen ORCID From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland. steffen.pfeuffer@neuro.med.uni-giessen.de
Rolfes, Leoni
Autor Rolfes, Leoni From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Ingwersen, Jens
Autor Ingwersen, Jens From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Pul, Refik
Autor Pul, Refik From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Kleinschnitz, Konstanze
Autor Kleinschnitz, Konstanze From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Korsen, Melanie
Autor Korsen, Melanie From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Räuber, Saskia
Autor Räuber, Saskia ORCID From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Ruck, Tobias
Autor Ruck, Tobias From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Schieferdecker, Simon
Autor Schieferdecker, Simon From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Willison, Alice Grizzel
Autor Willison, Alice Grizzel From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Aktas, Orhan
Autor Aktas, Orhan ORCID From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Kleinschnitz, Christoph
Autor Kleinschnitz, Christoph ORCID From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Hartung, Hans-Peter
Autor Hartung, Hans-Peter From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Kappos, Ludwig
Autor Kappos, Ludwig From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland
Meuth, Sven G
Autor Meuth, Sven G From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic Department of Neurology (H.-P.H.), Medical University of Vienna, Austria Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

Neurology® neuroimmunology & neuroinflammation. 2023 ; 10 (3) : . [pub] 20230411

Neurol Neuroimmunol Neuroinflamm
ISSN 2332-7812
Medvik
Zdroj

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz https://www.medvik.cz/link/bmc23011547

Online Plný text

NLK Directory of Open Access Journals od 2014
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PubMed Central od 2014
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PubMed 37041077
DOI 10.1212/nxi.0000000000200104
Knihovny.cz E-zdroje

MeSH
antilymfocytární sérum MeSH
dospělí MeSH
lidé MeSH
prospektivní studie MeSH
recidiva MeSH
relabující-remitující roztroušená skleróza * farmakoterapie MeSH
roztroušená skleróza * farmakoterapie MeSH
výsledek terapie MeSH
Check Tag
dospělí MeSH
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
Geografické názvy
Spojené státy americké MeSH

BACKGROUND AND OBJECTIVES: B cell-depleting antibodies were proven as effective strategy for the treatment of relapsing multiple sclerosis (RMS). The monoclonal antibody ocrelizumab was approved in 2017 in the United States and in 2018 in the European Union, but despite proven efficacy in randomized, controlled clinical trials, its effectiveness in the real-world setting remains to be fully elucidated. In particular, most study patients were treatment naive or switched from injectable therapies, whereas oral substances or monoclonal antibodies made up >1% of previous treatments. METHODS: We evaluated ocrelizumab-treated patients with RMS enrolled in the prospective cohorts at the University Hospitals Duesseldorf and Essen, Germany. Epidemiologic data at baseline were compared, and Cox proportional hazard models were applied to evaluate outcomes. RESULTS: Two hundred eighty patients were included (median age: 37 years, 35% male patients). Compared with using ocrelizumab as a first-line treatment, its use as a third-line therapy increased hazard ratios (HRs) for relapse and disability progression, whereas differences between first- vs second-line and second- vs third-line remained smaller. We stratified patients according to their last previous disease-modifying treatment and here identified fingolimod (FTY) (45 patients, median age 40 years, 33% male patients) as a relevant risk factor for ongoing relapse activity despite 2nd-line (HR: 3.417 [1.007-11.600]) or 3rd-line (HR: 5.903 [2.489-13.999]) ocrelizumab treatment, disability worsening (2nd line: HR: 3.571 [1.013-12.589]; 3rd line: HR: 4.502 [1.728-11.729]), and occurrence of new/enlarging MRI lesions (2nd line: HR: 1.939 [0.604-6.228]; 3rd line: HR: 4.627 [1.982-10.802]). Effects were persistent throughout the whole follow-up. Neither peripheral B-cell repopulation nor immunoglobulin G levels were associated with rekindling disease activity. DISCUSSION: Our prospectively collected observational data suggest suboptimal effectiveness of ocrelizumab in patients switching from FTY compared with those switching from other substances or having been treatment naive. These findings support previous studies indicating abated effectiveness of immune cell-depleting therapies following FTY treatment in patients with RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RMS, previous treatment with FTY compared with previous treatment with other immunomodulating therapies decreases the effectiveness of ocrelizumab.

Brain and Mind Center University of Sydney NSW Australia

Department of Neurology and Centre for Translational Neuro and Behavioural Sciences University Hospital Essen Germany

Department of Neurology Medical University of Vienna Austria

Department of Neurology Palacky University Olomouc Czech Republic

Department of Neurology University Hospital Duesseldorf Germany

From the Department of Neurology University Hospital Giessen and Marburg Justus Liebig University Giessen

Neurologic Clinic and Policlinic Departments of Medicine Biomedicine and Clinical Research University Hospital Basel University of Basel Switzerland

Citace poskytuje Crossref.org

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100 1_: $a Pfeuffer, Steffen $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland. steffen.pfeuffer@neuro.med.uni-giessen.de $1 https://orcid.org/0000000151714845

245 10: $a Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab / $c S. Pfeuffer, L. Rolfes, J. Ingwersen, R. Pul, K. Kleinschnitz, M. Korsen, S. Räuber, T. Ruck, S. Schieferdecker, AG. Willison, O. Aktas, C. Kleinschnitz, HP. Hartung, L. Kappos, SG. Meuth

520 9_: $a BACKGROUND AND OBJECTIVES: B cell-depleting antibodies were proven as effective strategy for the treatment of relapsing multiple sclerosis (RMS). The monoclonal antibody ocrelizumab was approved in 2017 in the United States and in 2018 in the European Union, but despite proven efficacy in randomized, controlled clinical trials, its effectiveness in the real-world setting remains to be fully elucidated. In particular, most study patients were treatment naive or switched from injectable therapies, whereas oral substances or monoclonal antibodies made up >1% of previous treatments. METHODS: We evaluated ocrelizumab-treated patients with RMS enrolled in the prospective cohorts at the University Hospitals Duesseldorf and Essen, Germany. Epidemiologic data at baseline were compared, and Cox proportional hazard models were applied to evaluate outcomes. RESULTS: Two hundred eighty patients were included (median age: 37 years, 35% male patients). Compared with using ocrelizumab as a first-line treatment, its use as a third-line therapy increased hazard ratios (HRs) for relapse and disability progression, whereas differences between first- vs second-line and second- vs third-line remained smaller. We stratified patients according to their last previous disease-modifying treatment and here identified fingolimod (FTY) (45 patients, median age 40 years, 33% male patients) as a relevant risk factor for ongoing relapse activity despite 2nd-line (HR: 3.417 [1.007-11.600]) or 3rd-line (HR: 5.903 [2.489-13.999]) ocrelizumab treatment, disability worsening (2nd line: HR: 3.571 [1.013-12.589]; 3rd line: HR: 4.502 [1.728-11.729]), and occurrence of new/enlarging MRI lesions (2nd line: HR: 1.939 [0.604-6.228]; 3rd line: HR: 4.627 [1.982-10.802]). Effects were persistent throughout the whole follow-up. Neither peripheral B-cell repopulation nor immunoglobulin G levels were associated with rekindling disease activity. DISCUSSION: Our prospectively collected observational data suggest suboptimal effectiveness of ocrelizumab in patients switching from FTY compared with those switching from other substances or having been treatment naive. These findings support previous studies indicating abated effectiveness of immune cell-depleting therapies following FTY treatment in patients with RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RMS, previous treatment with FTY compared with previous treatment with other immunomodulating therapies decreases the effectiveness of ocrelizumab.

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700 1_: $a Rolfes, Leoni $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Ingwersen, Jens $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Pul, Refik $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Kleinschnitz, Konstanze $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Korsen, Melanie $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Räuber, Saskia $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland $1 https://orcid.org/0000000189015572

700 1_: $a Ruck, Tobias $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Schieferdecker, Simon $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Willison, Alice Grizzel $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Aktas, Orhan $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland $1 https://orcid.org/0000000220209210

700 1_: $a Kleinschnitz, Christoph $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland $1 https://orcid.org/0000000216508875

700 1_: $a Hartung, Hans-Peter $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Kappos, Ludwig $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

700 1_: $a Meuth, Sven G $u From the Department of Neurology (S.P.), University Hospital Giessen and Marburg, Justus-Liebig-University Giessen; Department of Neurology (L.R., J.I., M.K., S.R., T.R., S.S., A.G.W., O.A., H.-P.H., S.G.M.), University Hospital Duesseldorf, Germany; Brain and Mind Center (H.-P.H.), University of Sydney, NSW, Australia; Department of Neurology (H.-P.H.), Palacky University, Olomouc, Czech Republic; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Department of Neurology and Centre for Translational Neuro- and Behavioural Sciences (C-TNBS) (R.P., K.K., C.K.), University Hospital Essen, Germany; and Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland

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