1College of Pharmacy, Gachon University, Incheon, 406-799, Korea.
Background: Hepatitis C virus infection is a worldwide health problem and one of the leading causes of cirrhosis and hepatocellular carcinoma. Recently, sofosbuvir was introduced to the therapeutic arsenal against this virus, thereby paving the way for all-oral regimen.
Aims: of the review This study aimed to systematically analyze the efficacy and safety of sofosbuvir for the treatment of hepatitis C virus infection.
Method: PubMed and EMBASE database searches were conducted using "sofosbuvir" as the search term. Phase III clinical studies retrieved from the two databases and resources posted on the Drug@FDA and ClinicalTrials.gov websites were evaluated with regard to outcomes of the efficacy and safety analyses of the drug.
Results: Eight Phase III clinical studies compared the efficacy and safety of sofosbuvir. When sofosbuvir replaced peginterferon which was used in the previous standard regimen, a superior sustained virologic response, as defined by a viral RNA load less than the lower limit of quantification 12 weeks after cessation of therapy, was obtained (74.3 vs. 66.7 %, p < 0.05). The response improved even more (90.8 vs. 66.7 %, p < 0.0001) when sofosbuvir was used as an add-on therapy to the standard regimen. The overall odds ratio to achieve the response in the sofosbuvir-containing arm of the eight clinical studies was 3.66 times greater (95 % CI 3.00-4.46) than that of the standard regimen arm. During the eight clinical studies, adverse events were observed in 83.61 and 87.22 % of the patients in the sofosbuvir and non-sofosbuvir arms, respectively, with the most frequent events being mild central nervous system symptoms such as fatigue, headache, and asthenia.
Conclusions: Sofosbuvir was safe and effective in the treatment of hepatitis C virus genotype 1, 2, 3, or 4 infections. However, the lack of persistence of the sustained virologic response beyond the study duration and long-term safety concerns need to be addressed in future studies.