Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in real world hepatitis C patients

Abstract

BACKGROUND The hepatitis C virus (HCV) NS5A inhibitor ABT-267 (ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450 (paritaprevir, PTV), the CYP3A inhibitor ritonavir (r) and the non-nucleoside NS5B polymerase inhibitor ABT-333 (dasabuvir, DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1 (GT1) infected patients. Patients with HCV who are considered “hard-to-cure” have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures. AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials. METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1 (GT1a, GT1b or GT1a/1b). Patients were treatment-naïve or previously failed a regimen including pegylated interferon/RBV +/- telaprevir, boceprevir, or simeprevir. One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/- RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment. RESULTS Many of the patients studied had comorbidities (44.2% hypertensive, 33.7% obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority (88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue (12%), headache (10%), insomnia (9%) and diarrhea (8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all (98%) patients were treatment compliant. CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV is highly effective and tolerable and results in better mental and physical health following treatment.

Clinical and Patient-Reported Outcomes of Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C Among Patients on Opioid Agonist Treatment: A Real-world Prospective Cohort Study

“…Still, compared with the findings of a post hoc analysis of phase 3 clinical trial data on PROs among OAT patients in antiviral treatment [ 19 ], the improvements in our study were modest, especially with regard to the PCS of the SF-12. However, as smaller improvements were also found in other real-world populations [ 33 , 34 ], 1 explanation might be that the exclusion of “difficult-to-treat” patients from registration trials results in better PROs. In our sample, health-related quality of life (PCS and MCS) at baseline was substantially reduced compared with the general population, which is consistent with a recent German large-scale study among OAT patients [ 35 ].…”

Effectiveness of retreatment with ombitasvir/paritaprevir/ritonavir and dasabuvir+sofosbuvir+ribavirin in patients with chronic hepatitis C, subtype 1b, and cirrhosis, who failed previous treatment with first‐ and second‐generation NS5A inhibitors

“…Several studies were dedicated to the question of 3D±RBV effectiveness in patients infected with HCV GT 1b who had earlier failed treatment with first‐ or second‐generation NS3 inhibitors (telaprevir + PEG + RBV or boceprevir + PEG + RBV or SIM + PEG + RBV), including 87.4% subjects with liver cirrhosis. Retreatment during 12 and 24 weeks in such patients resulted in the high likelihood of achieving SVR 96.2%–99.0% 25–27 …”

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

“…Redzicka et al [129] research work is based on design, synthesis, molecular docking simulations, and anti-inflammatory activity of series of pyrrolo [3,4-c]pyrrole. According to the results, compounds (45)(46)(47) have shown strong activity toward COX-1 and COX-2. Furthermore, single-crystal X-ray diffraction was recorded for (48).…”

“…This drug inhibits NS3/4A, a serine protease encoded by HCV genotype 1 and SARS-CoV-2 3CL proteases. Also, this drug is used with pegylated interferon and ribavirin for clinical trials [44][45][46] (Fig. 4).…”