REFILE-Sofosbuvir, simeprevir combo effective for HCV in patients with cirrhosis

Reuters Health Information: REFILE-Sofosbuvir, simeprevir combo effective for HCV in patients with cirrhosis

REFILE-Sofosbuvir, simeprevir combo effective for HCV in patients with cirrhosis

Last Updated: 2015-08-07

(Corrects spelling of simeprevir in headline and last paragraph)

By Joan Stephenson PhD

NEW YORK (Reuters Health) - Combination treatment with sofosbuvir and simeprevir results in high rates of sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) genotype 1 infection and cirrhosis who have contraindications to peginterferon and/or ribavirin, according to a retrospective analysis.

"This means that patients with cirrhosis and sometimes advanced cirrhosis can be successfully treated and achieve an SVR and be cured of HCV," Dr. Mitchell L. Shiffman, director of the Bon Secours Health System's Liver Institute of Virginia, told Reuters Health by email.

"Prior to the availability of oral antiviral agents for HCV, these patients could not be treated," Dr. Shiffman said, which meant liver transplantation had been the only remaining option for patients with HCV and cirrhosis. "The previous treatment, peginterferon and ribavirin, had too many side effects for this patient population."

The researchers analyzed data for 120 consecutive patients (mean age 60 years, 63% male) with chronic HCV genotype 1 (69% genotype 1A) and cirrhosis who were treated for 12 weeks with a combination of sofosbuvir and simeprevir between December 2013 and April 2014.

Nearly half (49%) of the patients were treatment naive. At baseline, 30% of the patients had laboratory evidence of liver decompensation or portal hypertension, and one-third had moderate or advanced cirrhosis (Child class B or C).

SVR at 12 weeks after completion of treatment (the primary endpoint) was 81% in the intention-to-treat population and the overall relapse rate was 14%. By per-protocol analysis, the SVR was 87%, with a relapse rate of 13%, the authors reported online July 28 in the American Journal of Gastroenterology.

However, the effectiveness of sofosbuvir-simeprevir treatment diminished with worsening cirrhosis, with Child class being the only baseline factor associated with SVR by multifactor analysis. The SVR in patients with Child class A, B, and C was 87%, 77%, and 67% respectively.

About 11% of patients experienced complications of cirrhosis or a worsening of liver function during the 12-week treatment period. These included sepsis, variceal bleeding, and hepatocellular carcinoma (two patients each), which the authors attributed to cirrhosis and not the medications, and eight patients with a marked elevation in serum bilirubin, which was believed to be related to simeprivir.

Two patients with Child class B cirrhosis at the time treatment was initiated and who had achieved SVR at 12 weeks tested positive for HCV RNA 24 weeks after completion of therapy. Although it's unclear whether patients with advanced cirrhosis are at higher risk for relapse more than 12 weeks after the completion of therapy, this finding "stresses the importance of monitoring all patients with cirrhosis for HCV RNA six months and possibly 12 months after HCV treatment has been completed," the authors noted.

Most of the patients who experienced relapse were subsequently retreated with an alternative antiviral combination (ledipasvir-sofosbuvir) that was not available when the patients were initially treated, said Dr. Shiffman.

"The results of the study are encouraging and support prior work suggesting that this combination of medications is an efficacious and safe way to treat patients with certain HCV genotypes, even if they have advanced liver disease," Dr. David Thomas, director of the division of infectious diseases at John Hopkins Medicine, told Reuters Health by email. "At the same time, clearly lower response rates in persons with advanced cirrhosis underscores the importance of treating persons far before they develop cirrhosis."

The study had no commercial funding. Gilead (the manufacturer of sofosbuvir) has financial relationships with the study's four authors; Janssen (which manufactures simeprevir) has financial relationships with two of them.

SOURCE: http://bit.ly/1ILDous

Am J Gastroenterol 2015

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