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Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

2019· article· en· W2977065657 on OpenAlexaff
Abhishek Kavati, Maryia Zhdanava, Benjamin Ortiz, Jason Lecocq, Bradd Schiffman, Dominic Pilon, Harriet Ho, Patrick Lefèbvre, Brian Stone

Bibliographic record

VenueClinical Therapeutics · 2019
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsGroup for Research in Decision Analysis
FundersNovartis Pharmaceuticals Corporation
KeywordsMedicineExhaled nitric oxideOmalizumabAsthmaBronchiectasisInternal medicineCystic fibrosisAllergyBiomarkerGastroenterologyImmunoglobulin ELungImmunologySpirometry

Abstract

fetched live from OpenAlex

PurposeBiomarkers, including blood eosinophils (EoS) and fractional exhaled nitric oxide (FeNO), may affect omalizumab outcomes in allergic asthma, but evidence in the literature remains mixed. This study assessed omalizumab outcomes in real-world patients with allergic asthma stratified by pretreatment biomarker levels.MethodsPatients with allergic asthma aged ≥12 years initiated on omalizumab with ≥12 months of data after index were identified in the Allergy Partners electronic medical records (2007–2018). Patients with ≥1 diagnosis of chronic obstructive pulmonary disease in combination with ≥10 pack-years of smoking, cystic fibrosis, Alpha-1 antitrypsin deficiency, bronchiectasis, interstitial lung disease, and sarcoidosis in the 12 months before or after index were excluded. Patients were stratified by pretreatment EoS (≥/<300 cells/μL) and FeNO (≥/<25 parts per billion). Outcomes, including Asthma Control Test (ACT) scores, forced expiratory volume in 1 second (FEV1), and FEV1 as a percentage of predicted value (FEV1% predicted), were compared using generalized estimating equations at 6 and 12 months after versus before index date in stratified patients with outcome measures available at both time periods.FindingsA total of 77 and 86 patients were stratified into the high and low EoS strata, respectively, and 56 patients into each of the intermediate-high and low FeNO strata. Compared with 6 months before index, mean difference (MD) in ACT scores at 6 months after index reached the minimally important difference of ≥3 points in high (MD = 3.75; 95% CI, 2.05–5.45) and low (MD = 4.56; 95% CI, 2.86–6.26) EoS, as well in the intermediate-high (MD = 3.75; 95% CI, 1.95–5.55) and low (MD = 3.55; 95% CI, 1.53–5.57) FeNO strata. Statistically significant improvements in mean FEV1 were observed in the high EoS (MD = 0.22 L/s; 95% CI, 0.08–0.35 L/s) and intermediate-high FeNO (MD = 0.13 L/s; 95% CI, 0.03–0.24 L/s) strata but not in the lower strata. In terms of mean FEV1% predicted, a statistically significant improvement was observed in high EoS stratum (MD = 4.95%; 95% CI, 0.60%–9.30%). Results that compared 12 months after versus before index date were similar.ImplicationsOmalizumab was associated with statistically significant improvements in ACT scores largely reaching or exceeding minimally important difference across biomarker levels and with a statistically significant improvement in lung function more evident in high biomarker strata. Although response varied by biomarkers for some outcomes, all strata indicated improvements on ≥1 measure. Real-world patients with allergic asthma could benefit from omalizumab regardless of pretreatment biomarker levels, suggesting that pretreatment biomarker levels might not inform response.

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 score0.008
Threshold uncertainty score0.316

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 head0.035
GPT teacher head0.342
Teacher spread0.308 · 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".

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Citations19
Published2019
Admission routes1
Has abstractyes

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