Published online May 14, 2019. doi: 10.3748/wjg.v25.i18.2229
Peer-review started: February 6, 2019
First decision: March 14, 2019
Revised: March 21, 2019
Accepted: April 10, 2019
Article in press: April 10, 2019
Published online: May 14, 2019
The hepatitis C virus (HCV) is a prevalent virus that, if left untreated, leads to chronic liver disease and, ultimately, death. The new era of direct acting antiviral (DAA) treatment regimens has the potential to cure the virus [i.e., achieve sustained virologic response (SVR)] in the majority of patients. The HCV NS5A inhibitor ombitasvir (OBV), HCV NS4/4A protease inhibitor paritaprevir (PTV), the CYP3A inhibitor ritonavir and the non-nucleoside NS5B polymerase inhibitor dasabuvir (DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a DAA regimen that achieves SVR rates as high as 99% in HCV genotype 1 (GT1) patients in controlled clinical studies. However, there are patients who are considered “hard to cure” that are traditionally excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures. This phase 4, open label study evaluated the safety and efficacy of OBV/PTV/r + DSV +/- RBV in a real-world clinical setting in patients who have historically been excluded from clinical trials. This study is completed.
Controlled clinical studies demonstrate 99% SVR rates in patients with HCV GT1, however, many patients in these studies do not meet the inclusion criteria for these studies. In a real world population of HCV patients, many have comorbidities or history of previous HCV treatment failures. We sought to examine the efficacy and safety of OBV/PTV/r + DSV +/- RBV in real world HCV patients who are generally underrepresented in clinical trials. This study also examined patient quality of life, dosing adherence and whether resistance-associated substitutions (RASs) impact achievement of SVR, which are all real world issues encountered in HCV patients. The results of this study will determine if controlled clinical trial results can be expected in everyday HCV patients seen in clinical practice.
The primary objective of this study was to examine the efficacy and safety of OBV/PTV/r + DSV +/- RBV in real world HCV patients generally underrepresented in clinical trials. This study found that this treatment regimen was highly effective and no adverse events were considered serious; these results are comparable to those seen in controlled clinical trials with this treatment regimen. Therefore, including patients with comorbidities or a history of previous HCV treatment(s) did not affect the results. According to this one study, the results demonstrated in controlled clinical trials involving OBV/PTV/r + DSV +/- RBV can be applied to everyday HCV patients seen in clinical practice.
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.
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.
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.
Results of he approved use of the OBV/PTV/r + DSV +/- RBV regimen in HCV GT1 patients in clinical practice can potential mirror results obtained in controlled clinical trials. The availability of real world data on approved HCV treatment regimens is extremely useful in clinical practice. Newer DAA regimens with shorter treatment durations have been recently approved. These regimens should also be evaluated in the real world population of HCV patients. Future clinical studies need to evaluate the efficacy and safety of these newer DAA regimens in real world patients. Patients with comorbidities and those who have had previous HCV treatment failures should be included in these studies. In addition, secondary measures should include physical and mental outcomes, the affects of RASs and adherence to the newer regimens.