LIVER MEETING 2013

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Older patients with hepatitis C experienced more adverse events and more serious adverse events while treated with boceprevir or telaprevir, and they discontinued treatment more frequently than did their younger peers, according to data from the HCV-TARGET trial.

Dr. Andrew Aronsohn of the University of Chicago and his colleagues studied a subset of HCV-TARGET that comprised 1,100 patients who started treatment on a direct-acting antiviral agent before April 2012.

Most patients were aged younger than 65 years; 73 were older. Of those, 56 were treated with telaprevir and 17 with boceprevir, Dr. Aronsohn reported at the annual meeting of the American Association for the Study of Liver Diseases.

In the older group, the median age was 67 years; 53% were women. Three-fifths had been treated previously for their hepatitis C infection (HCV).

Seniors were more likely to have diabetes, coronary artery disease, and inferior renal function than were their younger peers, though not significantly so. The rate of cirrhosis in both younger and older patients was roughly the same, at just over 40%.

Treatment response was similar for older and younger patients for both drugs. Sustained virologic response (SVR) to boceprevir in treatment-naive patients was 67% for older patients and 57% for younger patients. For treatment experienced patients, the rates were 36% and 37%, respectively.

SVR to telaprevir in treatment-naive patients was 75% for older patients vs. 60% for younger patients. In treatment-experienced patients, SVR was 53% vs. 59%, respectively.

A greater percentage of older patients discontinued treatment early – 44% vs. 36%.

Nearly all (94%) older patients treated with boceprevir became anemic; 18%, or 3 patients, were classified as having severe anemia, requiring either hospitalization for their anemia or expedited reporting of the adverse event to the Food and Drug Administration. In comparison, 63% of younger patients became anemic, with 6% classified as severe.

In patients treated with telaprevir, 77% of older patients became anemic compared with 65% of younger patients. Anemia was classified as severe in 9% of older patients and 3% of younger ones.

"Seven baseline characteristics were association with anemia," Dr. Aronsohn said. Age was independently associated with developing anemia.

He cautioned that while viral kinetics and treatment outcomes were similar for older and younger patients, adverse events – particularly anemia – and early discontinuation pose a concern in patients aged older than 65 years.

HCV-TARGET is a consortium of more than 100 academic and community medical centers performing a longitudinal, observational study. Treatment is not standardized and is administered per the local standard of care. The investigators seek to capture clinical, adverse event, virological, and demographic data on patients treated for hepatitis C.

Dr. Aronsohn’s conflicts of interest were not available at press time. HCT-TARGET is sponsored by Vertex Pharmaceuticals, Merck, Genentech, and Kadmon Pharmaceuticals.

dfulton@frontlinemedcom.com

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

emechcatie@frontlinemedcom.com

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

emechcatie@frontlinemedcom.com

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

emechcatie@frontlinemedcom.com

WASHINGTON – Results from a planned interim analysis show that using a combination of simeprevir and sofosbuvir as hepatitis C therapy achieved slightly higher sustained viral response in HCV genotype 1–infected patients at 4 and 12 weeks post treatment, suggesting that it may not be necessary to add in ribavirin.

That’s according to lead author Dr. Ira M. Jacobson, medical director of the Center for the Study of Hepatitis C at the Weill Cornell Medical College, New York, who spoke at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Dr. Jacobson presented results from the four-arm, two-cohort, phase IIa COSMOS (Combination of Simeprevir and Sofosbuvir in HCV Genotype 1–Infected Patients) study. He reported on the final sustained viral response (SVR)12 for both arms of cohort 1 and the interim SVR4 for the 12-week arms of cohort 2. The two cohorts were enrolled simultaneously.

Patients were randomized to simeprevir 150 mg once daily plus sofosbuvir 400 mg once daily either with or without ribavirin for 12 or 24 weeks. Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir. Sofosbuvir is an investigational nucleotide inhibitor developed by Gilead Sciences.

Cohort 1, with 80 patients, had a METAVIR score of F0-F2 and had previously not responded to pegylated interferon plus ribavirin. METAVIR is an algorithm for establishing degree of fibrosis, with 0 being no fibrosis and 4 being cirrhosis. There were four arms of cohort 1: 24 patients received the triple drug regimen for 24 weeks, 15 received simeprevir plus sofosbuvir for 24 weeks, 27 received the triple therapy for 12 weeks, and 14 were given simeprevir plus sofosbuvir for 12 weeks.

Cohort 2, with 87 patients, consisted of treatment-naive or prior null responders and those with a METAVIR score of F3-F4. In the four arms studied, 30 received triple therapy for 24 weeks, 16 received simeprevir plus sofosbuvir for 24 weeks, 27 got triple therapy for 12 weeks, and 14 received simeprevir plus sofosbuvir for 12 weeks. There was an even split in each arm between treatment-naive and null responders.

At the planned interim analysis, all patients in both cohorts had completed 12 weeks of therapy. In cohort 1, all patients – with the exception of three in the first arm and one in the second arm – had completed 24 weeks of therapy. All cohort 2 patients were continuing on study drugs, with the exception of two patients who discontinued triple therapy and one who stopped taking the combination of simeprevir plus sofosbuvir.

In cohort 1, 96% of those who took triple drug therapy for 12 weeks achieved an SVR12, compared with 93% of those on the dual-drug regimen. The SVR12 in those who received 24 weeks of therapy was 79% for triple therapy and 93% for dual therapy.

For cohort 2, the SVR4 for dual therapy was 100% after 12 weeks of treatment, compared with 96% for the triple therapy. All treatment-naive patients achieved an SVR4 while taking either triple or dual therapy. All prior null responders taking dual therapy also achieved an SVR4, while only 93% of those on the triple therapy achieved an SVR4.

When looked at by HCV GT1 subtype, the results show that patients with the Q80K polymorphism did not fare as well. In cohort 1, 89% of patients with that polymorphism achieved an SVR12, compared with 100% of those with GT1a or 1b without Q80K. In cohort 2, 91% of those with the polymorphism achieved an SVR4, compared with 100% of the patients with GT1a or 1b who did not have Q80K.

The most common adverse events were fatigue, headache, and nausea. Adverse events occurred in 70% of patients in the 12-week treatment group and 90% in the 24-week group. Three patients had a serious adverse event.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously backed simeprevir for approval in combination with pegylated interferon and ribavirin for chronic HCV GT1 infection in adults with compensated liver disease, including cirrhosis, who are treatment naive or have failed previous interferon-based therapy. The FDA advisers said that the simeprevir regimen would likely be easier to manage than the first-generation protease inhibitors currently approved for treating chronic HCV, telaprevir and boceprevir, which require 6-12 pills daily.

The agency is expected to rule on simeprevir’s approval by Nov. 27.

Janssen paid for the study. Dr. Jacobson reported that he receives grants or research support from, serves on the speakers bureaus of, or acts as a consultant to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, and other companies.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Results from a planned interim analysis show that using a combination of simeprevir and sofosbuvir as hepatitis C therapy achieved slightly higher sustained viral response in HCV genotype 1–infected patients at 4 and 12 weeks post treatment, suggesting that it may not be necessary to add in ribavirin.

That’s according to lead author Dr. Ira M. Jacobson, medical director of the Center for the Study of Hepatitis C at the Weill Cornell Medical College, New York, who spoke at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Dr. Jacobson presented results from the four-arm, two-cohort, phase IIa COSMOS (Combination of Simeprevir and Sofosbuvir in HCV Genotype 1–Infected Patients) study. He reported on the final sustained viral response (SVR)12 for both arms of cohort 1 and the interim SVR4 for the 12-week arms of cohort 2. The two cohorts were enrolled simultaneously.

Patients were randomized to simeprevir 150 mg once daily plus sofosbuvir 400 mg once daily either with or without ribavirin for 12 or 24 weeks. Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir. Sofosbuvir is an investigational nucleotide inhibitor developed by Gilead Sciences.

Cohort 1, with 80 patients, had a METAVIR score of F0-F2 and had previously not responded to pegylated interferon plus ribavirin. METAVIR is an algorithm for establishing degree of fibrosis, with 0 being no fibrosis and 4 being cirrhosis. There were four arms of cohort 1: 24 patients received the triple drug regimen for 24 weeks, 15 received simeprevir plus sofosbuvir for 24 weeks, 27 received the triple therapy for 12 weeks, and 14 were given simeprevir plus sofosbuvir for 12 weeks.

Cohort 2, with 87 patients, consisted of treatment-naive or prior null responders and those with a METAVIR score of F3-F4. In the four arms studied, 30 received triple therapy for 24 weeks, 16 received simeprevir plus sofosbuvir for 24 weeks, 27 got triple therapy for 12 weeks, and 14 received simeprevir plus sofosbuvir for 12 weeks. There was an even split in each arm between treatment-naive and null responders.

At the planned interim analysis, all patients in both cohorts had completed 12 weeks of therapy. In cohort 1, all patients – with the exception of three in the first arm and one in the second arm – had completed 24 weeks of therapy. All cohort 2 patients were continuing on study drugs, with the exception of two patients who discontinued triple therapy and one who stopped taking the combination of simeprevir plus sofosbuvir.

In cohort 1, 96% of those who took triple drug therapy for 12 weeks achieved an SVR12, compared with 93% of those on the dual-drug regimen. The SVR12 in those who received 24 weeks of therapy was 79% for triple therapy and 93% for dual therapy.

For cohort 2, the SVR4 for dual therapy was 100% after 12 weeks of treatment, compared with 96% for the triple therapy. All treatment-naive patients achieved an SVR4 while taking either triple or dual therapy. All prior null responders taking dual therapy also achieved an SVR4, while only 93% of those on the triple therapy achieved an SVR4.

When looked at by HCV GT1 subtype, the results show that patients with the Q80K polymorphism did not fare as well. In cohort 1, 89% of patients with that polymorphism achieved an SVR12, compared with 100% of those with GT1a or 1b without Q80K. In cohort 2, 91% of those with the polymorphism achieved an SVR4, compared with 100% of the patients with GT1a or 1b who did not have Q80K.

The most common adverse events were fatigue, headache, and nausea. Adverse events occurred in 70% of patients in the 12-week treatment group and 90% in the 24-week group. Three patients had a serious adverse event.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously backed simeprevir for approval in combination with pegylated interferon and ribavirin for chronic HCV GT1 infection in adults with compensated liver disease, including cirrhosis, who are treatment naive or have failed previous interferon-based therapy. The FDA advisers said that the simeprevir regimen would likely be easier to manage than the first-generation protease inhibitors currently approved for treating chronic HCV, telaprevir and boceprevir, which require 6-12 pills daily.

The agency is expected to rule on simeprevir’s approval by Nov. 27.

Janssen paid for the study. Dr. Jacobson reported that he receives grants or research support from, serves on the speakers bureaus of, or acts as a consultant to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, and other companies.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Results from a planned interim analysis show that using a combination of simeprevir and sofosbuvir as hepatitis C therapy achieved slightly higher sustained viral response in HCV genotype 1–infected patients at 4 and 12 weeks post treatment, suggesting that it may not be necessary to add in ribavirin.

That’s according to lead author Dr. Ira M. Jacobson, medical director of the Center for the Study of Hepatitis C at the Weill Cornell Medical College, New York, who spoke at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Dr. Jacobson presented results from the four-arm, two-cohort, phase IIa COSMOS (Combination of Simeprevir and Sofosbuvir in HCV Genotype 1–Infected Patients) study. He reported on the final sustained viral response (SVR)12 for both arms of cohort 1 and the interim SVR4 for the 12-week arms of cohort 2. The two cohorts were enrolled simultaneously.

Patients were randomized to simeprevir 150 mg once daily plus sofosbuvir 400 mg once daily either with or without ribavirin for 12 or 24 weeks. Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir. Sofosbuvir is an investigational nucleotide inhibitor developed by Gilead Sciences.

Cohort 1, with 80 patients, had a METAVIR score of F0-F2 and had previously not responded to pegylated interferon plus ribavirin. METAVIR is an algorithm for establishing degree of fibrosis, with 0 being no fibrosis and 4 being cirrhosis. There were four arms of cohort 1: 24 patients received the triple drug regimen for 24 weeks, 15 received simeprevir plus sofosbuvir for 24 weeks, 27 received the triple therapy for 12 weeks, and 14 were given simeprevir plus sofosbuvir for 12 weeks.

Cohort 2, with 87 patients, consisted of treatment-naive or prior null responders and those with a METAVIR score of F3-F4. In the four arms studied, 30 received triple therapy for 24 weeks, 16 received simeprevir plus sofosbuvir for 24 weeks, 27 got triple therapy for 12 weeks, and 14 received simeprevir plus sofosbuvir for 12 weeks. There was an even split in each arm between treatment-naive and null responders.

At the planned interim analysis, all patients in both cohorts had completed 12 weeks of therapy. In cohort 1, all patients – with the exception of three in the first arm and one in the second arm – had completed 24 weeks of therapy. All cohort 2 patients were continuing on study drugs, with the exception of two patients who discontinued triple therapy and one who stopped taking the combination of simeprevir plus sofosbuvir.

In cohort 1, 96% of those who took triple drug therapy for 12 weeks achieved an SVR12, compared with 93% of those on the dual-drug regimen. The SVR12 in those who received 24 weeks of therapy was 79% for triple therapy and 93% for dual therapy.

For cohort 2, the SVR4 for dual therapy was 100% after 12 weeks of treatment, compared with 96% for the triple therapy. All treatment-naive patients achieved an SVR4 while taking either triple or dual therapy. All prior null responders taking dual therapy also achieved an SVR4, while only 93% of those on the triple therapy achieved an SVR4.

When looked at by HCV GT1 subtype, the results show that patients with the Q80K polymorphism did not fare as well. In cohort 1, 89% of patients with that polymorphism achieved an SVR12, compared with 100% of those with GT1a or 1b without Q80K. In cohort 2, 91% of those with the polymorphism achieved an SVR4, compared with 100% of the patients with GT1a or 1b who did not have Q80K.

The most common adverse events were fatigue, headache, and nausea. Adverse events occurred in 70% of patients in the 12-week treatment group and 90% in the 24-week group. Three patients had a serious adverse event.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously backed simeprevir for approval in combination with pegylated interferon and ribavirin for chronic HCV GT1 infection in adults with compensated liver disease, including cirrhosis, who are treatment naive or have failed previous interferon-based therapy. The FDA advisers said that the simeprevir regimen would likely be easier to manage than the first-generation protease inhibitors currently approved for treating chronic HCV, telaprevir and boceprevir, which require 6-12 pills daily.

The agency is expected to rule on simeprevir’s approval by Nov. 27.

Janssen paid for the study. Dr. Jacobson reported that he receives grants or research support from, serves on the speakers bureaus of, or acts as a consultant to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, and other companies.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – The use of the experimental drug sofosbuvir in combination with ribavirin successfully reduced hepatitis C virus infection recurrence in 77% of posttransplant patients 4 weeks after treatment ended, based on the initial results of an ongoing large, prospective multicenter study.

HCV recurrence is the most common cause of mortality and graft loss following transplantation, and 10%-50% of those with a recurrent infection progress to cirrhosis within 5 years, Dr. Michael R. Charlton, professor of medicine at the Mayo Clinic, Rochester, Minn., said at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Sofosbuvir, manufactured by Gilead Sciences, is a nucleotide analogue inhibitor of the NS5B polymerase enzyme, which plays an important role in HCV replication. The compound is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6.

There are no approved treatments currently in the United States to prevent posttransplant HCV recurrence.

Dr. Charlton reported results for 40 patients in an ongoing open-label interferon-free study. Their mean age was 59 years, with a range of 49-75 years; 78% were male, 85% were white, 8% were black, and 3% were Hispanic. Thirty-five patients (88%) had been previously treated, with 9 of the 40 having been previously treated with protease inhibitors. The study enrollees had a mean baseline HCV RNA of 6.55 log₁₀ IU/mL. Sixteen patients (40%) had cirrhosis. The predominant genotype was 1a, found in 22 patients (55%); 11 had genotype 1b, 6 had genotype 3, and 1 had genotype 4.

In the study, posttransplant patients with recurrent HCV infection of any genotype were included. The transplant had to have occurred between 6 and 150 months prior to enrollment. Patients had to have an absence of rejection and were excluded if they took more than 5 mg of prednisone daily. Study participants were given up to 24 weeks of sofosbuvir in a daily dose of 400 mg and ribavirin starting at 400 mg daily. The ribavirin dose was increased up to 1,200 mg daily, depending on the patient’s hemoglobin levels.

At week 4 of the study, all 40 patients were HCV RNA negative. At the end of treatment, 39 of the patients who were still in the trial were HCV negative. Four weeks post treatment, 27 of 35 were negative.

Of the nine patients who relapsed post treatment, eight were male, five were genotype 1a, three were genotype 1b, and one was genotype 4. Eight of the nine had prior treatment. And five had bridging fibrosis or cirrhosis.

There were no episodes of rejection, and there were no interactions that required adjustment of immunosuppressive therapy.

The most common side effects were fatigue, arthralgia, headache, and diarrhea. Six patients had a serious adverse event. Two patients withdrew as a result of a serious adverse event, but the events were not related to sofosbuvir, said Dr. Charlton.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously recommended the approval of sofosbuvir for two indications: in combination with pegylated interferon and ribavirin, for treatment-naive adults with genotype 1 and 4 infections and in combination with ribavirin, for adults with genotype 2 and 3 infections.

If approved, as is expected, the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland, and Turkey, according to Gilead.

Dr. Charlton disclosed that he has received research support and consulting fees from a variety of companies, including AbbeVie, Biotest, Bristol Myers-Squibb, Gilead, Novartis, and Vertex.

The study was funded by Gilead Sciences.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – The use of the experimental drug sofosbuvir in combination with ribavirin successfully reduced hepatitis C virus infection recurrence in 77% of posttransplant patients 4 weeks after treatment ended, based on the initial results of an ongoing large, prospective multicenter study.

HCV recurrence is the most common cause of mortality and graft loss following transplantation, and 10%-50% of those with a recurrent infection progress to cirrhosis within 5 years, Dr. Michael R. Charlton, professor of medicine at the Mayo Clinic, Rochester, Minn., said at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Sofosbuvir, manufactured by Gilead Sciences, is a nucleotide analogue inhibitor of the NS5B polymerase enzyme, which plays an important role in HCV replication. The compound is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6.

There are no approved treatments currently in the United States to prevent posttransplant HCV recurrence.

Dr. Charlton reported results for 40 patients in an ongoing open-label interferon-free study. Their mean age was 59 years, with a range of 49-75 years; 78% were male, 85% were white, 8% were black, and 3% were Hispanic. Thirty-five patients (88%) had been previously treated, with 9 of the 40 having been previously treated with protease inhibitors. The study enrollees had a mean baseline HCV RNA of 6.55 log₁₀ IU/mL. Sixteen patients (40%) had cirrhosis. The predominant genotype was 1a, found in 22 patients (55%); 11 had genotype 1b, 6 had genotype 3, and 1 had genotype 4.

In the study, posttransplant patients with recurrent HCV infection of any genotype were included. The transplant had to have occurred between 6 and 150 months prior to enrollment. Patients had to have an absence of rejection and were excluded if they took more than 5 mg of prednisone daily. Study participants were given up to 24 weeks of sofosbuvir in a daily dose of 400 mg and ribavirin starting at 400 mg daily. The ribavirin dose was increased up to 1,200 mg daily, depending on the patient’s hemoglobin levels.

At week 4 of the study, all 40 patients were HCV RNA negative. At the end of treatment, 39 of the patients who were still in the trial were HCV negative. Four weeks post treatment, 27 of 35 were negative.

Of the nine patients who relapsed post treatment, eight were male, five were genotype 1a, three were genotype 1b, and one was genotype 4. Eight of the nine had prior treatment. And five had bridging fibrosis or cirrhosis.

There were no episodes of rejection, and there were no interactions that required adjustment of immunosuppressive therapy.

The most common side effects were fatigue, arthralgia, headache, and diarrhea. Six patients had a serious adverse event. Two patients withdrew as a result of a serious adverse event, but the events were not related to sofosbuvir, said Dr. Charlton.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously recommended the approval of sofosbuvir for two indications: in combination with pegylated interferon and ribavirin, for treatment-naive adults with genotype 1 and 4 infections and in combination with ribavirin, for adults with genotype 2 and 3 infections.

If approved, as is expected, the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland, and Turkey, according to Gilead.

Dr. Charlton disclosed that he has received research support and consulting fees from a variety of companies, including AbbeVie, Biotest, Bristol Myers-Squibb, Gilead, Novartis, and Vertex.

The study was funded by Gilead Sciences.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – The use of the experimental drug sofosbuvir in combination with ribavirin successfully reduced hepatitis C virus infection recurrence in 77% of posttransplant patients 4 weeks after treatment ended, based on the initial results of an ongoing large, prospective multicenter study.

HCV recurrence is the most common cause of mortality and graft loss following transplantation, and 10%-50% of those with a recurrent infection progress to cirrhosis within 5 years, Dr. Michael R. Charlton, professor of medicine at the Mayo Clinic, Rochester, Minn., said at the annual meeting of the American Association for the Study of Liver Diseases.

Alicia Ault/IMNG Medical Media

Sofosbuvir, manufactured by Gilead Sciences, is a nucleotide analogue inhibitor of the NS5B polymerase enzyme, which plays an important role in HCV replication. The compound is active against HCV genotypes 1 (the most common genotype in the United States), 2, 3, 4, 5, and 6.

There are no approved treatments currently in the United States to prevent posttransplant HCV recurrence.

Dr. Charlton reported results for 40 patients in an ongoing open-label interferon-free study. Their mean age was 59 years, with a range of 49-75 years; 78% were male, 85% were white, 8% were black, and 3% were Hispanic. Thirty-five patients (88%) had been previously treated, with 9 of the 40 having been previously treated with protease inhibitors. The study enrollees had a mean baseline HCV RNA of 6.55 log₁₀ IU/mL. Sixteen patients (40%) had cirrhosis. The predominant genotype was 1a, found in 22 patients (55%); 11 had genotype 1b, 6 had genotype 3, and 1 had genotype 4.

In the study, posttransplant patients with recurrent HCV infection of any genotype were included. The transplant had to have occurred between 6 and 150 months prior to enrollment. Patients had to have an absence of rejection and were excluded if they took more than 5 mg of prednisone daily. Study participants were given up to 24 weeks of sofosbuvir in a daily dose of 400 mg and ribavirin starting at 400 mg daily. The ribavirin dose was increased up to 1,200 mg daily, depending on the patient’s hemoglobin levels.

At week 4 of the study, all 40 patients were HCV RNA negative. At the end of treatment, 39 of the patients who were still in the trial were HCV negative. Four weeks post treatment, 27 of 35 were negative.

Of the nine patients who relapsed post treatment, eight were male, five were genotype 1a, three were genotype 1b, and one was genotype 4. Eight of the nine had prior treatment. And five had bridging fibrosis or cirrhosis.

There were no episodes of rejection, and there were no interactions that required adjustment of immunosuppressive therapy.

The most common side effects were fatigue, arthralgia, headache, and diarrhea. Six patients had a serious adverse event. Two patients withdrew as a result of a serious adverse event, but the events were not related to sofosbuvir, said Dr. Charlton.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously recommended the approval of sofosbuvir for two indications: in combination with pegylated interferon and ribavirin, for treatment-naive adults with genotype 1 and 4 infections and in combination with ribavirin, for adults with genotype 2 and 3 infections.

If approved, as is expected, the second indication will mark the first approval of a treatment for chronic hepatitis C with an interferon-free regimen, and it will be the first drug in its class to be approved. The FDA is expected to make a decision by Dec. 8. Sofosbuvir also is under review in the European Union, Australia, Canada, New Zealand, Switzerland, and Turkey, according to Gilead.

Dr. Charlton disclosed that he has received research support and consulting fees from a variety of companies, including AbbeVie, Biotest, Bristol Myers-Squibb, Gilead, Novartis, and Vertex.

The study was funded by Gilead Sciences.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

Alicia Ault/IMNG Medical Media

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

Alicia Ault/IMNG Medical Media

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Using the ECHO model of primary care to treat hepatitis C is cost saving in 35% of patients and very cost effective overall, according to a retrospective analysis presented by Dr. John B. Wong, at the annual meeting of the American Association for the Study of Liver Diseases.

Project ECHO (Extension for Community Healthcare Outcomes) was begun at the University of New Mexico, Albuquerque, and has been adopted by the Veterans Affairs department, among other organizations, as a means of extending primary care to those who might not otherwise have access.

Alicia Ault/IMNG Medical Media

"This is not about the antiviral treatment, it’s about the engagement of primary care physicians, to train them, educate them, and help them take care of patients with hepatitis C," said Dr. Wong, chief of the division of clinical decision making at Tufts Medical Center, Boston. "It’s about increasing access," he added.

Dr. Wong presented the results of a cost-effectiveness analysis he and his Tufts colleagues conducted on a study of ECHO’s effectiveness in treating HCV, published in the New England Journal of Medicine in 2011 (N. Engl. J. Med. 2011;364:2199-207).

That prospective cohort study evaluated ECHO in the HCV treatment of 261 patients at 16 community sites and 5 prisons.

Dr. Wong and his colleagues updated the data, using information from the United Network for Organ Sharing; the Surveillance, Epidemiology and End Results Program; and life tables from the Centers for Disease Control and Prevention. They also used the previously established and validated Markov cohort simulation model to compare ECHO to no antiviral therapy for each of the 261 patients.

Costs taken into account included expenses for drugs, physician visits, lab tests, adverse events, HCV disease complications, and multidisciplinary ECHO personnel (physician, pharmacist, psychiatrist, nurse manager, coordinator, and user support analyst).

Dr. Wong said that the researchers also performed an analysis of the cost of antiviral treatment if patients traveled to the academic center to receive care instead of having ECHO come to them. Travel costs included mileage, patient time, and guard costs for prisoners. The investigators used quality-of-life adjustments to account for antiviral treatment and disease-related morbidity, and discounted costs and effectiveness at 3% a year.

They calculated that ECHO led to a 63% reduction in lifetime cirrhosis when compared with no antiviral therapy. Hepatocellular carcinoma declined by 45% and liver death by 46%. There was a 4.4-year gain in life expectancy overall, and a 5.5-year gain in quality-adjusted life expectancy.

For 42% of the 261 patients, the incremental effectiveness did not outweigh the cost – and the opportunity cost – of taking an antiviral, said Dr. Wong. In another 23% of patients, the antiviral therapy extended life, but in the end, when the costs of the disease and the antivirals were added in, there was an extra cost associated with the therapy.

But in 35% of the patients, there was an extension of life – as much as 8 additional years – and a reduction in cost of treatment, as much as $40,000.

The incremental cost-effectiveness ratio – a formula calculated by dividing the additional cost by the additional benefit – for ECHO is $3,700, Dr. Wong said. The World Health Organization considers anything less than the per capita gross domestic product of a country to be "very cost effective," and anything less than three times that per capita number to be "cost effective," he said. He noted that the mean GDP in the United States is $50,000, putting the ECHO intervention well within the WHO’s range for very cost effective.

The gains were even greater for patients living in correctional institutions, with an incremental cost-effectiveness ratio of $1,400.

The study is limited by the fact that it is a computer simulation, and some travel data were missing, said Dr. Wong.

Additional trials are needed to confirm the results, he said.

The University of New Mexico recently started an institute to spread the ECHO model.

Dr. Wong reported no conflicts of interest.

mailto:aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

emechcatie@frontlinemedcom.com

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

emechcatie@frontlinemedcom.com