1222ABT-450/r/Ombitasvir and Dasabuvir with Ribavirin Achieves High Sustained Virologic Response Rates Regardless of Baseline Characteristics: Pooled Analyses of the SAPPHIRE-I and SAPPHIRE-II Studies
Notice bibliographique
Résumé
Background. The 3 direct-acting antiviral (3D) regimen of ABT-450 (identified by AbbVie and Enanta) dosed with ritonavir (ABT-450/r), ombitasvir (formerly ABT-267), and dasabuvir (formerly ABT-333) with ribavirin (RBV) has achieved high rates of sustained virologic response 12 weeks post-treatment (SVR12) in HCV genotype 1-infected patients. The SVR12 rates based on pooled data from the SAPPHIRE-I and SAPPHIRE-II studies were assessed by baseline characteristics. Methods. HCV genotype 1-infected patients who were treatment-naïve or with previous non-response to pegIFN/RBV were enrolled into SAPPHIRE-I or SAPPHIRE-II, respectively. Patients were randomized 3:1 to receive co-formulated ABT-450/r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice daily) with weight-based ribavirin (1000–1200 mg daily) or matching placebos during the 12-week double-blind period. Data from the 2 studies were pooled to assess overall SVR12 and by baseline factors including sex, age, body mass index (BMI), HCV RNA, fibrosis status, HCV subtype, and IL28B genotype. Results. The overall SVR12 rate of 770 patients who received at least one dose of 3D + RBV was 96.2% (95% CI, 94.9–97.6). Similar SVR12 rates were achieved by treatment-naïve (96.2%, N = 473) and previously treated patients (96.3%, N = 297). SVR rates ranged 92.3–98.6% across all examined baseline subgroups (figure). Rates of SVR12 were similarly high in historically difficult to cure populations including those with IL28B non-CC genotype, and patients with F3 baseline fibrosis stage. Only baseline BMI was statistically significantly associated with SVR12 rates (P < 0.05), though patients with baseline BMI ≥ 30 kg/m3 achieved an SVR12 rate of 92.3%. Conclusion. Only baseline BMI ≥ 30 kg/m3 was significantly associated with a lower SVR12 rate (92.3%), however, was of limited clinical significance. Rates of SVR12 > 92% across all subgroups were observed in non-cirrhotic HCV genotype 1-infected patients previously untreated or experienced to pegIFN/RBV, including difficult to cure populations such as those with IL28B non-CC genotype, baseline HCV RNA >800,000 IU/mL, high BMI, and F3 baseline fibrosis stage. Disclosures. J. J. Feld, AbbVie: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Boehringer Ingelheim: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Gilead: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Roche: Grant Investigator, Research grant and Research support; Vertex: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; BMS: Consultant and Scientific Advisor, Consulting fee; Idenix: Consultant and Scientific Advisor, Consulting fee; Janssen: Consultant and Scientific Advisor, Consulting fee; Merck: Consultant and Scientific Advisor, Consulting fee O. Weiland, AbbVie: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Gilead: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; BMS: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Medivir: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Johnson & Johnson: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Merck: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium R. T. Marinho, AbbVie: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Gilead: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; BMS: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Roche: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Merck: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Janssen: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium H. Wedemeyer, Abbott: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; AbbVie: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Achillion: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; BMS: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Boehringer Ingelheim: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; GSK: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; ITS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Janssen: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Merck: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Novartis: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Roche: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Roche Diagnostics: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Siemens: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; Transgene: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium; MSD: Grant Investigator, Research support I. M. Jacobson, AbbVie: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; Achillion: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; BMS: Consultant, Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Boehringer Ingelheim: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; Roche: Consultant, Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Gilead: Consultant, Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Janssen: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; Novartis: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support; Vertex: Consultant, Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Enanta: Consultant and Scientific Advisor, Consulting fee Idenix: Consultant and Scientific Advisor, Consulting fee D. M. Jensen, AbbVie: Grant Investigator, Research grant and Research support; Boehringer Ingelheim: Grant Investigator, Research grant and Research support; BMS: Grant Investigator, Research grant and Research support; Roche/Genentech: Grant Investigator, Research grant and Research support; Pharmasset/Gilead: Grant Investigator, Research grant and Research support; Tibotec/Janssen: Grant Investigator, Research grant and Research support T. Hassanein, AbbVie: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Boehringer Ingelheim: Grant Investigator, Research grant; BMS: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium; Eisai: Grant Investigator, Research grant; Gilead: Grant Investigator and Speaker's Bureau, Research grant and Speaker honorarium; Janssen: Grant Investigator, Research grant; Idenix: Grant Investigator, Research grant; Ikaria: Grant Investigator, Research grant; Mochida: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Ocera: Grant Investigator, Research grant; Taigen: Grant Investigator, Research grant; Salix: Grant Investigator and Speaker's Bureau, Research grant and Speaker honorarium; Sundise: Grant Investigator, Research grant; Baxter: Speaker's Bureau, Speaker honorarium; Takeda: Grant Investigator, Research grant; Vertex: Grant Investigator, Research grant V. De Ledinghen, AbbVie: Scientific Advisor, Consulting fee; BMS: Scientific Advisor, Consulting fee; Gilead: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Janssen: Scientific Advisor, Consulting fee; Echosens: Scientific Advisor, Consulting fee M. Diago, AbbVie: Research Contractor, Research support; Boehringer Ingelheim: Research Contractor, Research support; BMS: Research Contractor and Speaker's Bureau, Research support and Speaker honorarium; Gilead: Research Contractor and Speaker's Bureau, Research support and Speaker honorarium; Janssen: Research Contractor and Speaker's Bureau, Research support and Speaker honorarium; Roche: Research Contractor and Speaker's Bureau, Research support and Speaker honorarium; MSD: Research Contractor and Speaker's Bureau, Research support and Speaker honorarium; Novartis: Research Contractor, Research support; Vertex: Research Contractor, Research support L. Magenta, AbbVie: Scientific Advisor, Consulting fee; MSD: Scientific Advisor, Consulting fee; Gilead: Scientific Advisor, Consulting fee; Janssen: Scientific Advisor, Consulting fee R. J. De Knegt, Gilead: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium; Janssen Cilag: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium; Norgine: Speaker's Bureau, Speaker honorarium; AbbVie: Scientific Advisor, Consulting fee; BMS: Grant Investigator and Scientific Advisor, Consulting fee and Research support; Merck: Scientific Advisor, Consulting fee; Roche: Grant Investigator and Scientific Advisor, Consulting fee and Research support; Medtronic: Grant Investigator, Research support J. J. Xiong, AbbVie: Employee and Shareholder, Salary E. Coakley, AbbVie: Employee and Shareholder, Salary T. Baykal, AbbVie: Employee and Shareholder, Salary F. Tatsch, AbbVie: Employee and Shareholder, Salary G. R. Foster, AbbVie: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; BMS: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Roche: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Gilead: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Novartis: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; Janssen: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Research grant and Research support; GSK: Consultant and Scientific Advisor, Consulting fee; Virco: Consultant and Scientific Advisor, Consulting fee; Vertex: Consultant and Scientific Advisor, Consulting fee
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 | 0,019 | 0,010 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,005 | 0,013 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».