Sofosbuvir/R yields benefits in compassionate use HCV program

SAN FRANCISCO – The direct-acting antiviral sofosbuvir plus ribavirin (SOF/R) improved liver function in patients with hepatitis C virus infection who were awaiting liver transplant and it produced a high sustained virologic response rate in those whose infection recurred after previous therapy, according to two reports from the same compassionate use program that were presented as late-breaker studies at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Both sets of data were characterized as evidence of the efficacy of SOF/R in a real-world setting for challenging forms of hepatitis C virus (HCV) infection. The first presentation involved data on 216 patients with decompensated cirrhosis who were awaiting transplant; in these patients, viral clearance with SOF/R “was associated with a significant improvement of liver function within months in a proportion of patients with advanced cirrhosis,” reported Dr. Silvia Martini, University of Turin, Italy.

In this part of the compassionate use program, all patients were given SOF/R until liver transplant or for a maximum of 48 weeks. In some patients, SOF/R was discontinued at the time of transplant, while others received SOF/R for a period after transplant.

In the pretreatment phase, there was only one patient who did not respond at all and one who developed breakthrough virologic failure. All of the others were responders who achieved nondetectable levels of HCV-RNA while on therapy. The median time to HCV-RNA clearance was 4 weeks with a range of 2 to 24 weeks.

In patients with a MELD (model for end-stage liver disease) score under 15 and a Child-Pugh score (an assessment of the prognosis of chronic liver disease) under 8 at baseline, no significant improvement in liver function was observed on SOF/R. However, in the 54 patients with a MELD score greater than or equal to 15 and the 56 patients with a Child-Pugh score greater than or equal to 8, MELD improved by greater than or equal to 3 points in 35% and Child-Pugh score improved by greater than or equal to 3 points in 28%. In 40% of patients, the MELD score fell below 15.

Of the 88 patients who went on to liver transplant, 56 patients stopped SOF/R at the time of transplant. Only 4% of those study participants who were HCV-RNA negative for more than 4 weeks relapsed. Of those negative for less than 4 weeks, 36% relapsed. In 32 patients SOF/R was continued for some time after transplant. To date, only 6% of these have relapsed since stopping therapy.

Most of the nine deaths that occurred during treatment were attributed to complications of cirrhosis. None were associated with SOF/R treatment. The most frequent adverse event was anemia, which was attributed to ribavirin. There were no serious adverse events observed.

Most of the patients in this study had genotype (GT) 1b (47%), but several other genotypes, including GT3 (22%), were represented. The median baseline MELD score was 13 (range 6-24) and the median Child-Pugh score was 8 (range 5-12).

It is notable that improvement in liver function was of sufficient magnitude in some patients that Dr. Martini suggested that it might be possible in some cases to “delist” those scheduled for liver transplant. Dr. Martini suggested further studies are needed to explore this possibility.

In the other late-breaker presentation based on this compassionate use program, called ITACOPS, the focus was on patients with recurrent hepatitis after prior treatment. Patients were also required to have significant fibrosis (METAVIR score F3-F4). Advanced cirrhosis was permitted but not required.

Of 330 patients who met these criteria and were treated with SOF/R for 24 weeks, the high sustained virologic response (SVR) 4 weeks after the end of treatment was 86.3%. SVR rates were higher in those with F3 METAVIR than those with F4 (93.5% vs. 85.3%; P = .033) and those with a Child-Pugh score of 5 or less than higher (92.7% vs. 76.4%; P = .002).

“This large real-life study indicates that SOF/R combination therapy for 24 weeks is a very effective and well tolerated treatment for recurrent HCV,” reported the lead investigator Dr. Paola Carrai, University of Pisa, Italy. However, she noted that SVR rates for recurrent HCV were most encouraging in those with less severe fibrosis and less advanced cirrhosis.

SAN FRANCISCO – The direct-acting antiviral sofosbuvir plus ribavirin (SOF/R) improved liver function in patients with hepatitis C virus infection who were awaiting liver transplant and it produced a high sustained virologic response rate in those whose infection recurred after previous therapy, according to two reports from the same compassionate use program that were presented as late-breaker studies at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Both sets of data were characterized as evidence of the efficacy of SOF/R in a real-world setting for challenging forms of hepatitis C virus (HCV) infection. The first presentation involved data on 216 patients with decompensated cirrhosis who were awaiting transplant; in these patients, viral clearance with SOF/R “was associated with a significant improvement of liver function within months in a proportion of patients with advanced cirrhosis,” reported Dr. Silvia Martini, University of Turin, Italy.

In this part of the compassionate use program, all patients were given SOF/R until liver transplant or for a maximum of 48 weeks. In some patients, SOF/R was discontinued at the time of transplant, while others received SOF/R for a period after transplant.

In the pretreatment phase, there was only one patient who did not respond at all and one who developed breakthrough virologic failure. All of the others were responders who achieved nondetectable levels of HCV-RNA while on therapy. The median time to HCV-RNA clearance was 4 weeks with a range of 2 to 24 weeks.

In patients with a MELD (model for end-stage liver disease) score under 15 and a Child-Pugh score (an assessment of the prognosis of chronic liver disease) under 8 at baseline, no significant improvement in liver function was observed on SOF/R. However, in the 54 patients with a MELD score greater than or equal to 15 and the 56 patients with a Child-Pugh score greater than or equal to 8, MELD improved by greater than or equal to 3 points in 35% and Child-Pugh score improved by greater than or equal to 3 points in 28%. In 40% of patients, the MELD score fell below 15.

Of the 88 patients who went on to liver transplant, 56 patients stopped SOF/R at the time of transplant. Only 4% of those study participants who were HCV-RNA negative for more than 4 weeks relapsed. Of those negative for less than 4 weeks, 36% relapsed. In 32 patients SOF/R was continued for some time after transplant. To date, only 6% of these have relapsed since stopping therapy.

Most of the nine deaths that occurred during treatment were attributed to complications of cirrhosis. None were associated with SOF/R treatment. The most frequent adverse event was anemia, which was attributed to ribavirin. There were no serious adverse events observed.

Most of the patients in this study had genotype (GT) 1b (47%), but several other genotypes, including GT3 (22%), were represented. The median baseline MELD score was 13 (range 6-24) and the median Child-Pugh score was 8 (range 5-12).

It is notable that improvement in liver function was of sufficient magnitude in some patients that Dr. Martini suggested that it might be possible in some cases to “delist” those scheduled for liver transplant. Dr. Martini suggested further studies are needed to explore this possibility.

In the other late-breaker presentation based on this compassionate use program, called ITACOPS, the focus was on patients with recurrent hepatitis after prior treatment. Patients were also required to have significant fibrosis (METAVIR score F3-F4). Advanced cirrhosis was permitted but not required.

Of 330 patients who met these criteria and were treated with SOF/R for 24 weeks, the high sustained virologic response (SVR) 4 weeks after the end of treatment was 86.3%. SVR rates were higher in those with F3 METAVIR than those with F4 (93.5% vs. 85.3%; P = .033) and those with a Child-Pugh score of 5 or less than higher (92.7% vs. 76.4%; P = .002).

“This large real-life study indicates that SOF/R combination therapy for 24 weeks is a very effective and well tolerated treatment for recurrent HCV,” reported the lead investigator Dr. Paola Carrai, University of Pisa, Italy. However, she noted that SVR rates for recurrent HCV were most encouraging in those with less severe fibrosis and less advanced cirrhosis.

SAN FRANCISCO – The direct-acting antiviral sofosbuvir plus ribavirin (SOF/R) improved liver function in patients with hepatitis C virus infection who were awaiting liver transplant and it produced a high sustained virologic response rate in those whose infection recurred after previous therapy, according to two reports from the same compassionate use program that were presented as late-breaker studies at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Both sets of data were characterized as evidence of the efficacy of SOF/R in a real-world setting for challenging forms of hepatitis C virus (HCV) infection. The first presentation involved data on 216 patients with decompensated cirrhosis who were awaiting transplant; in these patients, viral clearance with SOF/R “was associated with a significant improvement of liver function within months in a proportion of patients with advanced cirrhosis,” reported Dr. Silvia Martini, University of Turin, Italy.

In this part of the compassionate use program, all patients were given SOF/R until liver transplant or for a maximum of 48 weeks. In some patients, SOF/R was discontinued at the time of transplant, while others received SOF/R for a period after transplant.

In the pretreatment phase, there was only one patient who did not respond at all and one who developed breakthrough virologic failure. All of the others were responders who achieved nondetectable levels of HCV-RNA while on therapy. The median time to HCV-RNA clearance was 4 weeks with a range of 2 to 24 weeks.

In patients with a MELD (model for end-stage liver disease) score under 15 and a Child-Pugh score (an assessment of the prognosis of chronic liver disease) under 8 at baseline, no significant improvement in liver function was observed on SOF/R. However, in the 54 patients with a MELD score greater than or equal to 15 and the 56 patients with a Child-Pugh score greater than or equal to 8, MELD improved by greater than or equal to 3 points in 35% and Child-Pugh score improved by greater than or equal to 3 points in 28%. In 40% of patients, the MELD score fell below 15.

Of the 88 patients who went on to liver transplant, 56 patients stopped SOF/R at the time of transplant. Only 4% of those study participants who were HCV-RNA negative for more than 4 weeks relapsed. Of those negative for less than 4 weeks, 36% relapsed. In 32 patients SOF/R was continued for some time after transplant. To date, only 6% of these have relapsed since stopping therapy.

Most of the nine deaths that occurred during treatment were attributed to complications of cirrhosis. None were associated with SOF/R treatment. The most frequent adverse event was anemia, which was attributed to ribavirin. There were no serious adverse events observed.

Most of the patients in this study had genotype (GT) 1b (47%), but several other genotypes, including GT3 (22%), were represented. The median baseline MELD score was 13 (range 6-24) and the median Child-Pugh score was 8 (range 5-12).

It is notable that improvement in liver function was of sufficient magnitude in some patients that Dr. Martini suggested that it might be possible in some cases to “delist” those scheduled for liver transplant. Dr. Martini suggested further studies are needed to explore this possibility.

In the other late-breaker presentation based on this compassionate use program, called ITACOPS, the focus was on patients with recurrent hepatitis after prior treatment. Patients were also required to have significant fibrosis (METAVIR score F3-F4). Advanced cirrhosis was permitted but not required.

Of 330 patients who met these criteria and were treated with SOF/R for 24 weeks, the high sustained virologic response (SVR) 4 weeks after the end of treatment was 86.3%. SVR rates were higher in those with F3 METAVIR than those with F4 (93.5% vs. 85.3%; P = .033) and those with a Child-Pugh score of 5 or less than higher (92.7% vs. 76.4%; P = .002).

“This large real-life study indicates that SOF/R combination therapy for 24 weeks is a very effective and well tolerated treatment for recurrent HCV,” reported the lead investigator Dr. Paola Carrai, University of Pisa, Italy. However, she noted that SVR rates for recurrent HCV were most encouraging in those with less severe fibrosis and less advanced cirrhosis.