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Record W2804839304 · doi:10.1136/jnnp-2018-anzan.85

086 The rapid efficacy of natalizumab vs fingolimod in patients with active relapsing-remitting multiple sclerosis (RRMS): results from reveal, a randomised, head-to-head study

2018· article· en· W2804839304 on OpenAlexaff
Helmut Butzkueven, Douglas Jeffery, Douglas L. Arnold, Massimo Filippi, Jeroen J.G. Geurts, Qunming Dong, Nolan Campbell, Stephanie Licata, Pei‐Ran Ho

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2018
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsNeuroRx Research (Canada)Montreal Neurological Institute and Hospital
Fundersnot available
KeywordsFingolimodNatalizumabMedicineMultiple sclerosisRelapsing remittingHazard ratioInternal medicineProportional hazards modelExpanded Disability Status ScaleCumulative doseRandomized controlled trialConfidence intervalImmunology

Abstract

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Introduction REVEAL was designed as a 1 year, multicentre, randomised, rater- and sponsor-blinded, prospective study comparing natalizumab and fingolimod in patients with active RRMS. Although the study closed early (for non-safety/non-efficacy reasons), data permitted comparison of effects occurring shortly after treatment initiation. This analysis compares onset of efficacy with natalizumab and fingolimod in REVEAL. Methods Patients were randomised to open-label intravenous natalizumab 300 mg every 4 weeks (n=54) or oral fingolimod 0.5 mg once daily (n=54). Magnetic resonance imaging was scheduled every 4 weeks for the first 24 weeks and at weeks 36 and 52. Analyses included Kaplan-Meier and Cox regression, negative binomial regression (annualised relapse rate [ARR] and number of T1 gadolinium-enhancing [Gd+] lesions) and a negative binomial generalised estimating equation (cumulative Gd +lesions over time). Results As expected for a randomised study, patient characteristics and follow-up time (median 39 weeks) were generally similar between groups. Natalizumab patients were less likely than fingolimod patients to develop new Gd +lesions (for ≥1 lesion, cumulative probability 40.68% vs 57.99%; hazard ratio [HR]=1.678 [95% CI: 0.865 to 3.255]; p=0.1258; for ≥2 lesions, cumulative probability 11.54% vs 48.48%; HR=4.053 [95% CI: 1.474 to 11.144]; p=0.007). Natalizumab patients consistently had 63%–72% fewer Gd +lesions than fingolimod patients, with between-group differences apparent within 4 weeks and reaching significance by 12 weeks (p=0.030). ARR was 83% lower with natalizumab than with fingolimod (0.05 vs 0.29; p=0.023), and cumulative probability of relapse was 1.85% with natalizumab vs 22.28% with fingolimod (HR=12.184 [95% CI: 1.552 to 95.634]; p=0.017). Adverse events were consistent with known safety profiles. Conclusion These results suggest that natalizumab reduces disease activity more rapidly and to a greater extent than fingolimod in patients with active RRMS. Given the early study closure, available data did not permit primary endpoint evaluation, and interpretation of these results requires caution. Study Support Biogen.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.003
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.043
GPT teacher head0.297
Teacher spread0.254 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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".

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Citations1
Published2018
Admission routes1
Has abstractyes

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