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Late Breaking Abstract - Benralizumab reduces eosinophils and ANCA in sputum in EGPA

2024· article· en· W4404127316 on OpenAlexaff
Manali Mukherjee, Nadia Suray Tan, Chynna Huang, Brian Kim, Katherine Radford, Carmen Venegas Garrido, Anurag Bhalla, Eva Rodríguez‐Suárez, Michael E. Wechsler, Brandie Walker, Lena Börjesson Sjö, Sofia Necander, Ali A. Ashkar, Julie Weidner, Roma Sehmi, Christopher McCrae, Nader Khalidi, Parameswaran Nair

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicEosinophilic Esophagitis
Canadian institutionsMcMaster Divinity CollegeUniversity of CalgaryMcMaster UniversityMcMaster University Medical Centre
Fundersnot available
KeywordsBenralizumabMedicineSputumImmunologyEosinophilAsthmaTuberculosisPathologyMepolizumab

Abstract

fetched live from OpenAlex

Introduction: Benralizumab (30mg subcutaneous Q4W) is noninferior to mepolizumab (300mg sc Q4W) to induce clinical remission in patients with refractory EGPA (PMID: 38393328). Aims: We evaluated if treatment arms were associated with eosinophil reduction and ANCA in sputum in the randomized, double-blind, head-to-head MANDARA trial ( NCT04157348 ). Methods: In a mechanistic sub-study (n=16) of the MANDARA trial, n=7 patients received benralizumab (52±11years, 57% female) and, n=9 received mepolizumab (58±16years, 78% female). Eosinophils, eosinophil activity (eosinophil peroxidase, EPX), T1/T2 cytokines and ANCA were assessed in blood and sputum pre- and post-treatment (PMID: 30179583). Results: Benralizumab reduced sputum eosinophils to <2.3% in 6/7 (86%) patients compared to mepolizumab (6/9, 66%) (χ2, P<0.01), but did not significantly reduce sputum EPX. At baseline, spANCA in both arms were comparable (mepo:4/9, 44%; benra: 3/7, 43%; only one sero-positive). Post-treatment, benralizumab significantly reduced spANCA levels compared to mepolizumab (P<0.05), with 2/7 (28%) remaining spANCA+. By comparison, there was an increase in the proportion of patients with spANCA on mepolizumab from baseline (6/9, 67%). Increase in spANCA correlated with spEPX (rho=0.65; P=0.01). The two patients on benralizumab who remained spANCA+ had elevated spEPX and ACQ-6≥1.5 at the time-point of sampling, despite having achieved clinical remission. Reduction of T2 cytokines was comparable in both arms. However, an increase in spIL-17A post-mepolizumab (P<0.05) was noted that correlated with an increase in spANCA. Conclusions: Benralizumab has a greater effect on reducing sputum eosinophils and ANCA levels in EGPA compared to mepolizumab.

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)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.048

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0140.001

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 head0.017
GPT teacher head0.299
Teacher spread0.282 · 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".

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Citations1
Published2024
Admission routes1
Has abstractyes

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