Evidence map›Paper›PMID 41420376›Full record

ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2026

Managing reactivation of multiple sclerosis during treatment with natalizumab.

Nathaniel Lizak, Sifat Sharmin, Dana Horáková, Eva Kubala Havrdova, Sara Eichau, Anneke van der Walt, Helmut Butzkueven, Jeannette Lechner-Scott, Katherine Buzzard, Olga Skibina and 27 more

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Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

37 authors.

Nathaniel LizakClinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.ORCID 0009-0009-3213-8390
Sifat SharminClinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Dana HorákováDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University, Prague, Czech Republic; General University Hospital, Prague, Czech Republic.ORCID 0000-0003-1915-0036
Eva Kubala HavrdovaDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University, Prague, Czech Republic; General University Hospital, Prague, Czech Republic.
Sara EichauDepartment of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain.ORCID 0000-0001-9159-3128
Anneke van der WaltDepartment of Neurology, The Alfred Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0002-4278-7003
Helmut ButzkuevenDepartment of Neurology, The Alfred Hospital, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0003-3940-8727
Jeannette Lechner-ScottHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia; Hunter New England Health, John Hunter Hospital, Newcastle, NSW, Australia.
Katherine BuzzardDepartment of Neurosciences, Box Hill Hospital, Melbourne, VIC, Australia; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia.
Olga SkibinaDepartment of Neurology, The Alfred Hospital, Melbourne, VIC, Australia; Department of Neurosciences, Box Hill Hospital, Melbourne, VIC, Australia; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia.
Oliver GerlachAcademic MS Center Zuyd, Department of Neurology, Zuyderland Medical Center, Heerlen, The Netherlands; School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
Alexandre PratCHUM MS Center and Universite de Montreal, Montreal, QC, Canada.
Marc GirardCHUM MS Center and Universite de Montreal, Montreal, QC, Canada.
Pierre DuquetteCHUM MS Center and Universite de Montreal, Montreal, QC, Canada.ORCID 0000-0001-7231-1754
Raed AlroughaniDivision of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait.
Francesco PattiDepartment of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.ORCID 0000-0002-6923-0846
Francois Grand'MaisonNeuro Rive-Sud, Longueuil, QC, Canada.
Maria José SáDepartment of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal; Instituto de Investigação, Inovação e Desenvolvimento Fernando Pessoa, Universidade Fernando Pessoa, Porto, Portugal; Faculdade de Ciências da Saúde (FCS-UFP), Universidade Fernando Pessoa, Porto, Portugal; Rede de Investigação em Saúde (RISE-UFP), Universidade Fernando Pessoa, Porto, Portugal.
Eduardo Aguera-MoralesDepartment of Medicine and Surgery, University Hospital Reina Sofia, Cordoba, Spain; Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.ORCID 0000-0002-8604-2054
Suzanne HodgkinsonImmune Tolerance Laboratory, Ingham Institute & Department of Medicine, UNSW, Sydney, NSW, Australia.
Pierre GrammondCISSS Chaudière-Appalache, Levis, QC, Canada.
Jens KuhleDepartment of Neurology, University Hospital & University of Basel, Basel, Switzerland; Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.ORCID 0000-0002-6963-8892
Bassem YamoutNeurology Institute, Harley Street Medical Center, Abu Dhabi, United Arab Emirates.
Samia J KhouryNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
Serkan OzakbasIzmir University of Economics, Medical Point Hospital, Izmir, Turkey.
Tunde CsepanyDepartment of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Nevin JohnDepartment of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Department of Neurology, Monash Health, Clayton, MO, Australia.ORCID 0000-0002-9834-4498
Guy LaureysDepartment of Neurology, University Hospital Ghent, Ghent, Belgium.
Murat TerziMedical Faculty, Mayis University, Samsun, Turkey.
Maria Pia AmatoDepartment NEUROFARBA, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Milano, Italy.ORCID 0000-0003-3325-3760
Cavit BozDepartment of Neurology, KTU Medical Faculty, Farabi Hospital, Trabzon, Turkey.
Abdullah Al-AsmiCollege of Medicine & Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Al-Khodh, Oman.
Elisabetta CartechiniNeurology Unit, P O Unico Macerata, Macerata, Italy.
Riadh GouiderDepartment of Neurology, LR 18SP03, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.ORCID 0000-0001-9615-3797
Saloua MrabetDepartment of Neurology, LR 18SP03, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Izanne RoosClinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.ORCID 0000-0003-0371-3666
Tomas KalincikClinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.ORCID 0000-0003-3778-1376

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFollowing natalizumab failure, it is unknown whether switching to alternative high-efficacy therapies offers superior effectiveness over continuing natalizumab.

objectiveTo compare different treatment strategies following natalizumab failure.

methodsPatients suffering a relapse during natalizumab treatment with adequate follow-up were identified from the MSBase registry. Following natalizumab failure, natalizumab continuation was compared to switching to anti-CD20 therapies/alemtuzumab/lower-efficacy therapies and treatment discontinuation. The primary outcome was the risk of further relapses. Secondary outcomes included risk of subsequent magnetic resonance imaging (MRI) activity, confirmed disability worsening and disease-activity-free survival. Multivariable proportional hazards models compared outcomes during time-varying therapy exposures. Four sensitivity analyses were conducted with varied inclusion criteria and treatment failure definitions.

resultsOf 1553 patients experiencing a relapse during natalizumab treatment, 1037 met the inclusion criteria. Following natalizumab failure, switch to anti-CD20 therapy was associated with a lower relapse risk (heart rate (HR) = 0.48, 95% confidence interval (CI) = 0.27-0.84) compared to continuing natalizumab; no differences were observed in MRI or disability outcomes. Treatment de-escalation or cessation was associated with increased relapse risk (HR = 1.46, 95% CI = 1.15-1.85; HR = 2.08, 95% CI = 1.22-3.55, respectively). We did not find evidence of a difference for switching to alemtuzumab. Sensitivity analyses replicated primary findings.

conclusionThis exploratory study indicates that switching to anti-CD20 therapies following natalizumab failure is associated with a >50% reduction in relapse risk. No differences were seen in secondary outcomes, despite consistent trends. Clinicians may consider anti-CD20 therapies following natalizumab failure, noting further research is needed to confirm differences in MRI and disability outcomes.

Indexed as

Immunologic FactorsMultiple SclerosisMultiple Sclerosis, Relapsing-RemittingNatalizumabAdultFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedRecurrenceRegistriesImmunologic FactorsNatalizumabdisease-modifying treatmentMultiple sclerosisnatalizumabrelapsestreatment failure

Identifiers

PMID41420376
PMCPMC12756529

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