Dupilumab Induces Clinical Remission in Children with Uncontrolled, Moderate-to-Severe, Type 2 Inflammatory Asthma
Bibliographic record
Abstract
Introduction: Sustained absence of exacerbations, normal lung function, controlled symptoms, and no systemic corticosteroid use in a 12-month period have been proposed as a composite multicomponent endpoint for on-treatment clinical remission in adults with asthma. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins 4/13, central drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959), dupilumab reduced annualized severe exacerbation rate and improved lung function and asthma control vs placebo in children aged 6 to 11 years with moderate-to-severe asthma and type 2 inflammation (baseline blood eosinophil count≥150 cells/μL or fractional exhaled nitric oxide≥20 ppb). Safety was consistent with the known dupilumab safety profile, with the addition of helminth infections. This post hoc analysis assessed the effect of dupilumab in achieving on-treatment clinical remission in children using a proposed composite, multicomponent endpoint. Methods: We evaluated the proportion of patients in VOYAGE meeting the composite endpoint for on-treatment clinical remission during 52 weeks on treatment using criteria: no exacerbations/use of oral corticosteroids; above the lower limit of normal for pre-bronchodilator ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (z-score>− 1.64) and pre-bronchodilator FEV1 (z-score>− 1.64); and 5-item Asthma Control Questionnaire (ACQ-5) score<0.75/<1.5. Results: The analysis included 350 children (placebo, n=114; dupilumab, n=236). At baseline, no children in either treatment group met the requirements for remission using ACQ-5<0.75. At Week 52 a significantly greater proportion of children treated with dupilumab vs placebo achieved clinical remission (41.9% vs 23.7%; P=0.0008). Similar results were seen using ACQ-5<1.5. Conclusion: Dupilumab vs placebo significantly increased the proportion of patients with uncontrolled, moderate-to-severe asthma and type 2 inflammation who met the proposed on-treatment clinical asthma remission composite endpoint by Week 52 of VOYAGE. Publication History Article published online: 28 February 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".