Exploring Global Geographic Variation in Exacerbation Rates in Randomized Controlled Trials of Biologics in Patients With Severe Asthma: A Systematic Literature Review
Notice bibliographique
Résumé
Abstract Rationale: Depemokimab is the first ultra-long-acting biologic with enhanced interleukin-5 binding affinity, high potency and extended half-life, enabling twice-yearly dosing for patients with asthma. In the Phase III SWIFT-1/2 studies, depemokimab significantly reduced exacerbations rates versus placebo; however, a high placebo response was seen in patients from Central East Europe. Previous reports have highlighted treatment effect differences across countries. This systematic literature review (SLR) summarized geographic variations in exacerbation rates and biologic treatment responses in randomized controlled trials (RCTs) enrolling patients with severe asthma. Methods: Following a predefined protocol, MEDLINE, Embase, and Evidence-based Medicine Reviews Databases were searched from inception to May 7, 2024, for RCTs of respiratory biologics for adult patients with severe asthma reporting exacerbation rates by geographic region. Key respiratory conferences (2019-2024) were also searched. Records were screened by one reviewer in two phases (abstract then full text), with 10% of screened publications validated by a second reviewer. Results were synthesized qualitatively. Results: Six publications reporting five unique trials reported on exacerbations by geographic region. Data from the SWIFT-1/2 studies were also included for reference. Subgroup and post hoc analyses by geographic region of RCTs for tezepelumab (NAVIGATOR), benralizumab (CALIMA/SIROCCO), reslizumab (NCT02452190), dupilumab (TRAVERSE open-label extension), and depemokimab (SWIFT-1/2) consistently reported the smallest treatment effects on exacerbation rates in Central East European countries (Table). Across four trials reporting arm-level exacerbation rates for tezepelumab, benralizumab, depemokimab, and dupilumab, patients from Central East Europe had the lowest exacerbation rates while on placebo. Only CALIMA and SIROCCO (benralizumab) reported patient baseline characteristics by geographic region, with patients from Central East Europe reporting the lowest exacerbation rate (suggesting less severe disease) of all regions in the year preceding study entry. While subgroup analyses of exacerbation rates by region were prespecified in most trials, some population sizes were small, limiting the ability to draw strong conclusions. Conclusions: Geographical variation in exacerbation rate was consistently observed across biologic RCTs in patients with severe asthma. Lower biologic treatment effects were observed in Central East Europe versus other regions due to lower exacerbation rates in the placebo arm. This could lead to misinterpretation of efficacy results if not considered in future studies. Further studies are needed to better understand how patient characteristics, background treatment adherence, clinical practice, and biologic access may affect the observed geographic differences in exacerbation rates, and how these may impact trial participation, and interpretation of trial results.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,052 | 0,175 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,017 | 0,015 |
| Bibliométrie | 0,020 | 0,018 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,004 | 0,004 |
| Science ouverte | 0,003 | 0,003 |
| Intégrité de la recherche | 0,003 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».