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Record W3164065928 · doi:10.1002/psp4.12647

Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy

2021· article· en· W3164065928 on OpenAlexaff
Michael A. Tortorici, Theresa Yuraszeck, David R. Cornblath, Vera Bril, Hans‐Peter Hartung, Gen Sobue, Richard A. Lewis, Ingemar S.J. Merkies, John‐Philip Lawo, Michaela Praus, Billie L. Durn, Orell Mielke, Xuewen Ma, Petra M. Jauslin, Marc Pfister, Ivo N. van Schaik

Bibliographic record

VenueCPT Pharmacometrics & Systems Pharmacology · 2021
Typearticle
Languageen
FieldMedicine
TopicPeripheral Neuropathies and Disorders
Canadian institutionsUniversity of TorontoUniversity Health Network
FundersSanofi GenzymeGrifolsMitsubishi Tanabe Pharma CorporationCSL BehringBaxaltaArgenxEuropean CommissionTG TherapeuticsSanofi
KeywordsChronic inflammatory demyelinating polyneuropathyDosingMedicineAntibodyPlaceboPolyradiculoneuropathyImmunoglobulin EImmunologyPopulationInternal medicinePolyneuropathyPharmacodynamicsPharmacokineticsImmunoglobulin GGastroenterologyGuillain-Barre syndromePathology

Abstract

fetched live from OpenAlex

Abstract The two main objectives of this analysis were to (i) characterize the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra ® ) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG pharmacokinetic (PK) parameters, including those from a previous population PK model, were used to predict individual IgG profile and exposure metrics. Treatment‐related changes in Inflammatory Neuropathy Cause and Treatment (INCAT) scores were best described by a maximum effect (E max ) model as a function of ΔIgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilization). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.

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)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Bibliometrics
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.088
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0070.026
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.002
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 head0.039
GPT teacher head0.386
Teacher spread0.347 · 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.

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

Citations5
Published2021
Admission routes1
Has abstractyes

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