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

Humans Male United States Adult Female Multiple Sclerosis, Relapsing-Remitting / drug therapy Prospective Studies Multiple Sclerosis / drug therapy Treatment Outcome Antilymphocyte Serum Recurrence

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
05 2023
Historique:
received: 27 05 2022
accepted: 27 01 2023
medline: 13 4 2023
entrez: 11 4 2023
pubmed: 12 4 2023
Statut: epublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1212/NXI.0000000000200104 PMID: 37041077 PMC: PMC10091366
pubmed: 37041077
pii: 10/3/e200104
doi: 10.1212/NXI.0000000000200104
pmc: PMC10091366
pii:
doi:

Substances chimiques

ocrelizumab A10SJL62JY
Antilymphocyte Serum 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Steffen Pfeuffer (S)

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.
ORCID: 0000-0001-5171-4845

Leoni Rolfes (L)

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.

Jens Ingwersen (J)

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.

Refik Pul (R)

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.

Konstanze Kleinschnitz (K)

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.

Melanie Korsen (M)

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.

Saskia Räuber (S)

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.
ORCID: 0000-0001-8901-5572

Tobias Ruck (T)

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.

Simon Schieferdecker (S)

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.

Alice Grizzel Willison (AG)

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.

Orhan Aktas (O)

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.
ORCID: 0000-0002-2020-9210

Christoph Kleinschnitz (C)

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.
ORCID: 0000-0002-1650-8875

Hans-Peter Hartung (HP)

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.

Ludwig Kappos (L)

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.

Sven G Meuth (SG)

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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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Nord › États-Unis › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Sclérose en plaques récurrente-rémittente › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Sérums immuns › Sérum antilymphocyte › Effect of Previous Disease-Modifying Therapy...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Récidive › Effect of Previous Disease-Modifying Therapy...