Efficacy of aclidinium/formoterol fixed-dose combination versus salmeterol/fluticasone in COPD
Notice bibliographique
Résumé
Background: Aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) twice daily (BID) is licensed in Europe for COPD treatment. Aim: To evaluate the efficacy of aclidinium/formoterol vs. salmeterol/fluticasone propionate FDC (SAL/FLU) in patients with COPD. Methods: A randomised, double-blind, Phase IIIb, 24-week study in patients with COPD Assessment Test (CAT) score ≥10 compared aclidinium/formoterol 400/12 µg BID via Genuair ® with SAL/FLU 50/500 µg BID via Accuhaler ® (NCT01908140). Endpoints were peak FEV 1 (primary), Transition Dyspnoea Index (TDI; secondary), CAT, device preference and exacerbations. Non-inferiority of aclidinium/formoterol vs. SAL/FLU was tested for peak FEV 1 and TDI. Superiority in peak FEV 1 was also analysed. Adverse events (AEs) were monitored throughout. Results: 933 patients were randomised: mean age 63.4 years; 65.1% male; mean post bronchodilator FEV 1 1.48 L (53.2% predicted); mean CAT score 18.5. 788 patients (84.5%) completed the study. Aclidinium/formoterol achieved greater peak FEV 1 vs. SAL/FLU from Day 1 to Week 24 (p < 0.0001; Table). Improvements in TDI, CAT and exacerbations were similar in both groups (Table). More patients preferred Genuair (51.9%) than Accuhaler (18.5%, p < 0.0001). The incidence of AEs, and AEs leading to study discontinuation was similar across groups. The most common AEs were COPD exacerbations (17.5%), headache (6.4%) and nasopharyngitis (5.8%). Conclusion: Superiority in peak FEV 1 and non-inferiority in TDI were demonstrated for aclidinium/formoterol FDC vs. SAL/FLU in patients with stable COPD. Improvements in quality of life and exacerbations were similar in both groups. More patients preferred Genuair to Accuhaler. Both treatments were well tolerated. Tab. 1: Efficacy of aclidinium/formoterol FDC vs. salmeterol/fluticasone FDC Aclidinium/formoterol 400/12 µg BID n = 468 Salmeterol/fluticasone 50/500 µg BID n = 463 Peak FEVi at baseline, L, mean (95% Cl) a 1.39 (1.34, 1.44) 1.38 (1.33, 1.43) PeakFEVi at Week 24, L, mean (95% Cl) b 1.66 (1.63, 1.68)"' 1.56 (1.54, 1.58) TDI focal score at Week 24, units, mean (95% Cl) b,c 1.88 (1.54, 2.21) 1.88 (1.54, 2.22) CAT total score at Week 24, units, mean (95% Cl) b 15.81 (15.23, 16.40) 16.11 (15.53, 16.70) Patients with ≥1 HCRU- defined exacerbation during study, % 15.8 16.6 Patients with ≥1 EXACT- identified exacerbation during study, % 37.8 39.5 Efficacy data were analysed in the intent-to-treat population with the exception of TDI focal score, which was analysed in the per-protocol population (non-inferiority analyses) 66 (14.1%) patients in the aclidinium/formoterol group and 79 (17.0%) in the salmeterol/fluticasone group did not complete the study Two patients randomised to aclidinium/formoterol 400/12 µg BID received salmeterol/fluticasone 50/500 µg BID; one patient randomised to salmeterol/fluticasone 50/500 µg BID received aclidinium/formoterol 400/12 µg BID. Efficacy data for these patients were analysed according to randomisation, safety data were analysed according to received treatment. a Absolute value b Data reported as least squares means c Per-protocol population: aclidinium/formoterol 400/12 µg BID n = 423; salmeterol/fluticasone 50/500 µg BID n = 414 ***p < 0.0001 vs. salmeterol/fluticasone 95% CI, 95% confidence interval; BID, twice daily; CAT, COPD Assessment Test; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FEV 1 , forced expiratory volume in 1 second; HCRU, healthcare resource utilisation; TDI, Transition Dyspnoea Index Funding This study was funded by Almirall S.A., Barcelona, Spain. Medical writing support, funded by AstraZeneca PLC, Barcelona, Spain, was provided by Richard Knight of Complete Medical Communications.
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 | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 ».