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Record W3162915930 · doi:10.1016/j.msard.2021.103012

The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

2021· article· en· W3162915930 on OpenAlexafffund
Johanna Balslev Andersen, Sifat Sharmin, Mathilde Lefort, Nils Koch‐Henriksen, Finn Sellebjerg, Per Soelberg Sørensen, Claudia C Hilt Christensen, Peter Vestergaard Rasmussen, Michael Broksgaard Jensen, Jette Lautrup Frederiksen, Stephan Bramow, Henrik Kahr Mathiesen, Karen Ingrid Schreiber, Dana Horáková, Eva Havrdová, Raed Alroughani, Guillermo Izquierdo, Sara Eichau, Serkan Özakbaş, Francesco Patti, Marco Onofrj, Alessandra Lugaresi, Murat Terzi, Pierre Grammond, Francois Grand’ Maison, Bassem Yamout, Alexandre Prat, Marc Girard, Pierre Duquette, Cavit Boz, María Trojano, Pamela McCombe, Mark Slee, Jeannette Lechner‐Scott, Recai Türkoğlu, Patrizia Sola, Diana Ferraro, Franco Granella, Vahid Shaygannejad, Julie Prévost, Olga Skibina, Claudio Solaro, Rana Karabudak, Bart Van Wijmeersch, Tünde Csépány, Daniele Spitaleri, Steve Vucic, Romain Casey, Marc Debouverie, Gilles Edan, Jonathan Ciron, Aurélie Ruet, de Sèze, Élisabeth Maillart, Hélène Zéphir, Pierre Labauge, Gilles Defer, Christine Lebrun‐Frénay, Thibault Moreau, Eric Berger, Pierre Clavelou, Jean Pelletier, Bruno Stankoff, Olivier Gout, Éric Thouvenot, Olivier Heinzlef, Bertrand Bourre, Olivier Casez, Philippe Cabre, Alexis Montcuquet, Abir Wahab, Jean‐Philippe Camdessanché, Aude Marousset, I. Patry, Karolina Hankiewicz, Corinne Pottier, Nicolas Maubeuge, Céline Labeyrie, Chantal Nifle, Emmanuelle Leray, David Laplaud, Helmut Butzkueven, Tomáš Kalinčík, Sandra Vukusic, Melinda Magyari

Bibliographic record

VenueMultiple Sclerosis and Related Disorders · 2021
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsCegep de Saint JeromeUniversité de MontréalHôpital Notre-DameCentre intégré de santé et de services sociaux de Chaudière-Appalaches
FundersNational Health and Medical Research CouncilCentre Hospitalier Universitaire de RennesSanofi GenzymeMultiple Sclerosis SocietyCentre Hospitalier Universitaire de NiceSanofiUniversité Claude Bernard Lyon 1Institut National de la Santé et de la Recherche MédicaleCanadian Institutes of Health ResearchCentre Hospitalier Universitaire de ToulouseMultiple Sclerosis Society of CanadaFondation pour l'Aide à la Recherche sur la Sclérose en PlaquesNovartisCelgeneFondazione Italiana Sclerosi MultiplaBiogenMedDay PharmaceuticalsGlaxoSmithKlineMerckTeva Pharmaceutical IndustriesUniversité de LorraineCentre Hospitalier Universitaire de BordeauxHospices Civils de LyonAgence Nationale de la RechercheRoche
KeywordsFingolimodNatalizumabMedicineMultiple sclerosisHazard ratioInternal medicineImmunologyConfidence interval

Abstract

fetched live from OpenAlex

BACKGROUND: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. METHODS: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. RESULTS: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. CONCLUSION: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.112
Threshold uncertainty score0.500

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.050
GPT teacher head0.333
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations12
Published2021
Admission routes2
Has abstractyes

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