Novel combination therapy may be effective for noncirrhotic HCV infection [UNITY-1 trial]

1. Amongst patients who were infected with hepatitis C genotype 1 and who did not have cirrhosis, receiving treatment with oral, three-drug combination therapy – daclatasvir , asunaprevir, and beclabuvir – led to a greater than 90% sustained virologic response at post-treatment week 12 (SVR12).

2. Even while evaluating the group separately based on prior treatment-naïve versus treatment-experienced (interferon, ribavirin, etc) status, the results were almost equally robust in the two cohorts.

Evidence Rating Level: 2 (Good)       

Study Rundown: Hepatitis C, which currently affects about 130-150 million people worldwide, causes significant morbidity and mortality through cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Current research is focusing on the treatment of this disease with all-oral, non-interferon based regimens. This study was conducted to determine the efficacy of a three-drug combination therapy – daclatasvir, asunaprevir, and beclabuvir – on the rate of sustained virologic response at post-treatment week 12 (SVR12) for a diagnosis of HCV genotype 1 in patients without cirrhosis. The results showed that greater than 90% of the patients achieved SVR12. Even while evaluating the group separately based on prior treatment-naïve versus treatment-experienced status, the results were almost equally robust in the two cohorts.

Strengths of the study include the multinational design and a clinically important primary outcome. The weaknesses include the lack of diversity in the treatment population, which limits the generalizability. Moreover, the uncontrolled, nonrandomized nature of the study does limit the reliability of the results. However, it would likely be unethical to include patients in a placebo group due to the nature of the disease.

Click to read the study, published today in JAMA

Relevant Reading: Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection

In-Depth [open label, uncontrolled trial]: This open label, nonrandomized, uncontrolled study utilized the following three-drug regimen – daclatasvir (NS5A protein inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B thumb-1 polymerase inhibitor). Enrolled patients came from the US, Canada, France, and Australia between December 2013 and August 2014. Patients received a fixed-dose regimen for 12 weeks, with a follow up period of 24 weeks afterwards. Eligibility criteria included noncirrhotic adults with HCV genotype 1 infection with a high HCV-RNA load who had either received no treatment, or had previously received treatment with therapies other than the ones included in this trial.

The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12). There were 415 total patients included in the study, 312 in the treatment-naïve group, and 103 in the treatment-experienced group. SVR12 was achieved by 379 of 415 patients (91.3%; 95%CI 88.6-94.0%). The rates remained almost equally high amongst the two cohorts: 92% amongst the treatment-naïve patients (95%CI 89.0-95.0%) and 89%% amongst treatment-experienced patients (95%CI 83.4-95.3%).

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