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Record W2805032224 · doi:10.1136/jnnp-2018-anzan.66

067 Efficacy of cladribine tablets in patients with highly active relapsing-remitting multiple sclerosis: analysis of pooled double-blind data from the clarity and onward studies

2018· article· en· W2805032224 on OpenAlexaff
Gavin Giovannoni, Xavier Montalbán, Kottil Rammohan, Stuart D. Cook, Giancarlo Comi, Per Soelberg Sørensen, Patrick Vermersch, Fernando Dangond, John King, Doris Damian

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2018
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of TorontoSt. Michael's Hospital
Fundersnot available
KeywordsMedicineCladribineMultiple sclerosisInternal medicinePlaceboPost-hoc analysisCohortLesionOdds ratioGastroenterologySurgeryPathologyPsychiatry

Abstract

fetched live from OpenAlex

Introduction Patients with relapsing MS (RMS) who show an increased rate of relapse or disability worsening can be described as showing high disease activity (HDA). Treatment with cladribine tablets (CT) in the CLARITY study, and with CT added to interferon-β in the ONWARD study demonstrated efficacy vs. placebo (PBO) across a range of patients with active MS. Combining double-blind data from these studies allows assessment of the efficacy of treatment with CT 3.5 mg/kg (CT3.5; cumulative dose). The objective of this post-hoc analysis is to compare the effects of CT3.5 vs. PBO on the proportion of patients achieving no evidence of disease activity (NEDA) status in HDA subgroups identified using two sets of criteria in a pooled cohort of patients from CLARITY and ONWARD. Methods Patients from CLARITY and ONWARD were retrospectively stratified using 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: high relapse activity (HRA; n=314) and HRA plus disease-activity-on-treatment (HRA +DAT; n=459). Patients treated with CT3.5 or PBO who fulfilled these criteria and achieved NEDA were compared over 2 years using odds ratios (ORs) and 95%CIs. Results In the HRA subgroup, 76.5% of CT3.5-treated patients were relapse-free, 86.7% were T1 Gd +lesion free vs. 50.7% and 35.8%, respectively, for PBO. In the HRA +DAT subgroup, 77.6% were relapse-free and 88.8% were T1 Gd +lesion free with CT3.5 vs. 53.9% and 40.8%, respectively for PBO. In the HRA and HRA +DAT subgroups, 42.7% and 41.3%, respectively, of CT3.5-treated patients were disease activity free compared with 9.7%, (OR 6.94, 95% CI 3.67;13.12, p<0.0001) and 13.7% (OR 4.28, 95% CI 2.62;6.99, p<0.0001) respectively, of PBO recipients. In the overall CLARITY+ONWARD population (including non-HDA patients), the composite NEDA score also favoured CT over PBO (OR 3.95, 95% CI 2.90;5.37, p<0.0001). Conclusion Compared with placebo, treatment with CT3.5 was associated with increased odds of achieving NEDA in HDA patients.

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)0.012
metaresearch head score (Gemma)0.011
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.064

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.011
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0040.006
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
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 head0.103
GPT teacher head0.337
Teacher spread0.235 · 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 designMeta-analysis
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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Citations0
Published2018
Admission routes1
Has abstractyes

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