High discontinuation rate noted for direct-acting antiviral therapy

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.