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
Bibliographic record
Abstract
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
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 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 | 0.019 | 0.010 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.013 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".