MétaCan
Menu
Back to cohort
Record W3193541681 · doi:10.3233/jnd-210665

A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment

2021· article· en· W3193541681 on OpenAlexfundno aff
Olga Mitelman, Hoda Abdel‐Hamid, Barry J. Byrne, Anne M. Connolly, Peter Heydemann, Crystal M. Proud, Perry B. Shieh, Kathryn R. Wagner, A. Dugar, Sourav Santra, James Signorovitch, Nathalie Goemans, Craig M. McDonald, Eugenio Mercuri, Jerry R. Mendell

Bibliographic record

VenueJournal of Neuromuscular Diseases · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsnot available
FundersNational Institute on Disability, Independent Living, and Rehabilitation ResearchNational Institute on Disability and Rehabilitation ResearchHebrew University of JerusalemNational Medical Research CouncilUniversitaire Ziekenhuizen Leuven, KU LeuvenBioMarin PharmaceuticalNational Institutes of HealthGrifolsItalfarmacoFibroGenAstellas PharmaFondazione TelethonUniversity of AlbertaSarepta TherapeuticsU.S. Department of DefenseEli Lilly and CompanyCSL BehringU.S. Department of EducationAlexion PharmaceuticalsBiogenPfizerParent Project Muscular DystrophyAveXisGlaxoSmithKlinePTC Therapeutics
KeywordsMedicineTerm (time)Prospective cohort studyRetrospective cohort studyPediatricsIntensive care medicineSurgery

Abstract

fetched live from OpenAlex

BACKGROUND: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. OBJECTIVE: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. METHODS: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. RESULTS: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p < 0.0001). CONCLUSIONS: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

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)0.000
metaresearch head score (Gemma)0.000
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 score0.035
Threshold uncertainty score0.535

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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)0.0000.000

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 head0.011
GPT teacher head0.274
Teacher spread0.262 · 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

Citations52
Published2021
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Neuromuscular DiseasesSame topicMuscle Physiology and DisordersFrench-language works237,207