Evidence map›Paper›PMID 37041077›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2023

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

Steffen Pfeuffer, Leoni Rolfes, Jens Ingwersen, Refik Pul, Konstanze Kleinschnitz, Melanie Korsen, Saskia Räuber, Tobias Ruck, Simon Schieferdecker, Alice Grizzel Willison and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. The Art of Sequencing Disease-Modifying Therapies in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 5 countries.

Steffen PfeufferFrom 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 RolfesFrom 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 IngwersenFrom 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 PulFrom 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 KleinschnitzFrom 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 KorsenFrom 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 RäuberFrom 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 RuckFrom 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 SchieferdeckerFrom 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 WillisonFrom 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 AktasFrom 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 KleinschnitzFrom 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 HartungFrom 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 KapposFrom 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 MeuthFrom 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.
The University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesB 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.

methodsWe 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.

resultsTwo 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.

Indexed as

Multiple SclerosisMultiple Sclerosis, Relapsing-RemittingAdultAntibodies, Monoclonal, HumanizedAntilymphocyte SerumFemaleHumansMaleProspective StudiesRecurrenceTreatment OutcomeUnited StatesAntibodies, Monoclonal, HumanizedAntilymphocyte Serumocrelizumab

Identifiers

PMID37041077
PMCPMC10091366
OpenAlexW4364356088

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.