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Record W4293522767 · doi:10.1016/j.ymgme.2022.08.007

Findings from the Morquio A Registry Study (MARS) after 6 years: Long-term outcomes of MPS IVA patients treated with elosulfase alfa

2022· article· en· W4293522767 on OpenAlexafffund
John J. Mitchell, Barbara K. Burton, Michael B. Bober, Philippe M. Campeau, Shelda Cohen, Sara Dosenovic, Carolyn Ellaway, Kaustuv Bhattacharya, Nathalie Guffon, David A. Hinds, Alice Lail, Shuan‐Pei Lin, Martin Magner, Julian Raiman, Liat Schwartz-Sagi, Karolina M. Stępień

Bibliographic record

VenueMolecular Genetics and Metabolism · 2022
Typearticle
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsCentre Hospitalier Universitaire Sainte-JustineMcGill University Health Centre
FundersMcGill UniversityBioMarin Pharmaceutical
KeywordsMedicineEnzyme replacement therapyConfidence intervalObservational studyInternal medicinePediatricsDisease

Abstract

fetched live from OpenAlex

The Morquio A Registry Study (MARS) is an ongoing, multinational, observational study of patients with MPS IVA. Key objectives of MARS are to characterize the heterogeneity and natural history of disease and to evaluate long-term effectiveness and safety of elosulfase alfa enzyme replacement therapy (ERT). Enrollment began in September 2014; data on medical history, clinical outcomes, and safety assessments are collected as part of routine care. As of February 2021, 381 subjects from 17 countries had enrolled in MARS: 58 ERT-naïve subjects and 323 ERT-treated subjects (≥1 infusion), with a mean ERT exposure of 5.5 years (SD 2.8) and median age at first ERT treatment of 9.8 years. ERT-treated subjects were younger at diagnosis (median 3.4 vs 6.5 years) relative to ERT-naïve subjects. Among ERT-treated subjects, urinary keratan sulfate (uKS) levels declined from pre-ERT baseline to last follow-up on treatment (mean % change [95% confidence interval]: −52.5% [−57.5%, −47.4%]; n = 115) and 6-min walk test distance remained stable (mean change: −6.1 [−27.6, 15.5] m; n = 131) over a mean follow-up of 5.5 years. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) increased in subjects who were < 18 years of age at ERT initiation (mean change: +0.3 [0.1, 0.4] L and + 0.4 [0.3, 0.5] L; mean follow-up: ∼6 years; n = 82) and were stable in subjects ≥18 years (mean change: 0.0 [−0.0, 0.1] L and 0.0 [−0.1, 0.1] L; mean follow-up: 4.6 years; n = 38). Overall, 148 (47.1%) ERT-treated subjects experienced ≥1 adverse event (AE) and 110 subjects (35%) reported ≥1 serious AE. Drug-related AEs were reported in 39 (12.4%) subjects; the most common were hypersensitivity (9 subjects [2.9%]), urticaria (8 subjects [2.5%]), and pyrexia (7 subjects [2.2%]). MARS is the longest and largest observational study of MPS IVA patients to date, with a heterogenous population that is representative of the MPS IVA population overall. Data collected over the first 6 years of MARS provide real-world evidence for long-term stabilization of endurance and respiratory function among ERT-treated patients, with no new safety concerns identified.

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 score0.005
Threshold uncertainty score0.515

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 head0.012
GPT teacher head0.263
Teacher spread0.251 · 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

Citations13
Published2022
Admission routes2
Has abstractyes

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