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Benralizumab attenuates blood and airway eosinophilia in severe asthmatics with inadequate response to anti-IL-5 neutralizing antibodies

2022· article· en· W4312847172 on OpenAlexaff
Manali Mukherjee, A Bhalla, Carmen Venegas-Garrido, C Huang, K Radford, M Kjarsgaard, Sylvia Lauks, K Son, N Lavigne, R Sehmi, Paul M. O’Byrne, P Nair

Bibliographic record

Venue05.01 - Airway pharmacology and treatment · 2022
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsMcMaster University
Fundersnot available
KeywordsBenralizumabMedicineEosinophiliaSputumMepolizumabImmunologyAsthmaPlaceboExhaled nitric oxidePrednisoneInternal medicineGastroenterologyEosinophilSpirometryTuberculosisPathology

Abstract

fetched live from OpenAlex

<b>Introduction:</b> Targeting the IL-5 ligand does not suppress airway eosinophilia in a subset of severe asthmatics. We investigated if targeting the IL-5 receptor with benralizumab would suppress airway eosinophilia leading to greater asthma control. <b>Methods:</b> Sixteen severe asthmatics (9 females, mean age 58±14 years) on daily high-dose corticosteroid therapy (14 prednisone-dependent, median dose 7.5 mg) with ACQ≥1.5 and sputum eosinophils&gt;3% despite mepolizumab (n=13, 100 mg, subcutaneous) or Reslizumab (n=3, 3mg/kg, intravenous) for ≥6 months were recruited in a sequential placebo-controlled trial (NCT03470311). Clinical outcomes were assessed at baseline (V1), after two months of placebo treatment (V3), and after 5 injections of benralizumab (V10). <b>Results:</b> Benralizumab completely depleted sputum and blood eosinophils in all 16 patients, with clinical improvements in FEV<sub>1</sub>, and ACQ-5 (Fig1). However, the decrease in fractional exhaled nitric oxide, FeNO (p&gt;0.05) was modest. Despite complete suppression of eosinophilia and mean decrease in asthma control questionnaire (ACQ-5) by 1.21 points, 37% (6/16) patients still documented ACQ &gt;1.5. <b>Conclusions:</b> Targeting IL-5R with benralizumab suppresses sputum and blood eosinophilia that is uncontrolled by anti-IL5 neutralizing antibodies in severe asthmatics. Residual symptoms, associated with raised FeNO may indicate IL-4R activity.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.073
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.015
GPT teacher head0.286
Teacher spread0.271 · 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

Citations1
Published2022
Admission routes1
Has abstractyes

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