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Record W2969550544 · doi:10.1101/735662

Immunotherapy prevents long-term disability in relapsing multiple sclerosis over 15 years

2019· preprint· en· W2969550544 on OpenAlexaff
Tomáš Kalinčík, Sifat Sharmin, Charles B. Malpas, Tim Spelman, Dana Horáková, Eva Havrdová, María Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Alexandre Prat, Marc Girard, Pierre Duquette, Pierre Grammond, Vilija Jokubaitis, Anneke van der Walt, François Grand’Maison, Patrizia Sola, Diana Ferraro, Vahid Shaygannejad, Raed Alroughani, Raymond Hupperts, Murat Terzi, Cavit Boz, Jeannette Lechner‐Scott, Eugenio Pucci, Vincent Van Pesch, Franco Granella, Roberto Bergamaschi, Daniele Spitaleri, Mark Slee, Steve Vucic, Radek Ampapa, Pamela McCombe, Cristina Ramo‐Tello, Julie Prévost, Javier Olascoaga, Edgardo Cristiano, Michael Barnett, Maria Luisa Saladino, José Luis Sánchez-Menoyo, Suzanne Hodgkinson, Csilla Rózsa, Stella Hughes, Fraser Moore, Cameron Shaw, Ernest Butler, Olga Skibina, Orla Gray, Allan G. Kermode, Tünde Csépány, Bhim Singhal, Neil Shuey, Piroska Imre, Bruce Taylor, Magdolna Simó, Carmen Adella Sîrbu, Attila Sas, Helmut Butzkueven

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsCegep de Saint JeromeJewish General HospitalCentre intégré de santé et de services sociaux de Chaudière-AppalachesUniversité de MontréalHôpital Notre-Dame
FundersNational Health and Medical Research CouncilTeva Pharmaceutical IndustriesBiogenMedical Research CouncilSanofi
KeywordsMedicineMultiple sclerosisHazard ratioConfidence intervalIncidence (geometry)Proportional hazards modelInternal medicinePediatricsCumulative incidencePhysical therapyImmunologyCohort

Abstract

fetched live from OpenAlex

ABSTRACT Objective Whether immunotherapy improves long-term disability in multiple sclerosis has not been satisfactorily demonstrated. This study examined the effect of immunotherapy on long-term disability outcomes in relapsing-remitting multiple sclerosis. Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the hazard of 12-month confirmed increase and decrease in disability, EDSS step 6 and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously re-adjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability and MRI activity. Results 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval 0.43–0.82, p=0.0016), worsening of disability (0.56, 0.38-0.82, p=0.0026) and progress to EDSS step 6 (0.33, 0.19-0.59, p=0.00019). Among 1085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p=10 -9 ) and worsening of disability (0.81, 0.67-0.99, p=0.043). Conclusions Continued treatment with multiple sclerosis immunotherapies reduces disability accrual (by 19-44%), the risk of need of a walking aid by 67% and the frequency of relapses (by 40-41%) over 15 years. A proof of long-term effect of immunomodulation on disability outcomes is the key to establishing its disease modifying properties.

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)0.001
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.044
GPT teacher head0.287
Teacher spread0.243 · 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 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

Citations2
Published2019
Admission routes1
Has abstractyes

Explore more

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