Real-world study: 8 weeks of two-drug combo highly effective against HCV

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.