Real‐world safety and effectiveness of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C virus genotype 1‐ and 4‐infected patients with diverse comorbidities and comedications: A pooled analysis of post‐marketing observational studies from 13 countries

• Published in: Journal of viral hepatitis 2019-06, Vol.26 (6), p.685-696
• Main Authors: Ferenci, Peter, Bourgeois, Stefan, Buggisch, Peter, Norris, Suzanne, Curescu, Manuela, Larrey, Dominique, Marra, Fiona, Kleine, Henning, Dorr, Patrick, Charafeddine, Mariem, Crown, Eric, Bondin, Mark, Back, David, Flisiak, Robert
• Format: Article
• Language: English
• Subjects: 2-Naphthylamine; Adolescent; Adult; Aged; Aged, 80 and over; Anilides - therapeutic use; Antipsychotics; Antiretroviral drugs; Antiviral Agents - therapeutic use; Antiviral drugs; Carbamates - therapeutic use; Cirrhosis; Clinical medicine; Clinical trials; comorbidity; Cyclopropanes; direct‐acting antiviral; Drug Interactions; Drug Therapy, Combination; drug‐drug interaction; Esophagus; Female; Genotype; Genotypes; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis; Hepatitis C; hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - epidemiology; Humans; Internationality; Lactams, Macrocyclic; Life Sciences; Liver cirrhosis; Macrocyclic Compounds - therapeutic use; Male; Middle Aged; Observational studies; Original; Patients; Peptic ulcers; Population studies; Proline - analogs & derivatives; Prospective Studies; real‐world evidence; Ribavirin; Ribavirin - therapeutic use; Ritonavir; Ritonavir - therapeutic use; Safety; Statins; Sulfonamides - therapeutic use; Sustained Virologic Response; Ulcers; Uracil - analogs & derivatives; Uracil - therapeutic use; Valine; Young Adult
• ISSN: 1352-0504; 1365-2893; 1365-2893
• DOI: 10.1111/jvh.13080

Summary Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) regimens show high efficacy and good tolerability in clinical trials for chronic hepatitis C virus (HCV) genotypes (GT) 1 or 4. To evaluate whether these results translate to clinical practice, data were pooled from observational studies across 13 countries. Treatment‐naïve or ‐experienced patients, with or without cirrhosis, received OBV/PTV/r ± DSV ± RBV according to approved local labels and clinical practice. Sustained virologic response at post‐treatment Week 12 (SVR12), adverse events (AEs) and comedication management were assessed for patients initiating treatment before 1 June 2017. The safety population included 3850 patients who received ≥1 dose of study drug. The core population (N = 3808) further excluded patients with unknown GT or cirrhosis status, or who received off‐label treatment. Patients had HCV GT1a (n = 732; 19%), GT1b (n = 2619; 69%) or GT4 (n = 457; 12%). In 3546 patients with sufficient follow‐up data at post‐treatment Week 12, the SVR12 rate was 96% (n/N = 3401/3546 [95% CI 95.2‐96.5]). In patients with or without cirrhosis, SVR12 was comparable (96%). In patients with HCV GT1a, GT1b or GT4, SVR12 rates were 93%, 97% and 94%. In GT1b‐infected patients with planned treatment for 8 weeks, SVR12 was 96%. In patients with ≥1 comorbidity (67%), SVR12 was 95%. 58% of patients received ≥1 comedication, and there was minimal impact on SVR12 rates using comedications for peptic ulcers and gastro‐esophageal reflux disease, statins, antipsychotics or antiepileptics. Most comedications were maintained during treatment although 58% of patients changed their statin medication. AEs and serious AEs occurred in 26% and 3% of patients. Post‐baseline Grade 3‐4 laboratory abnormalities were rare (