Clinicians, patients don’t want antivirals
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Undetectable viral load cut HCV morbidity, mortality

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

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Many patients and clinicians are "unenthusiastic" about antivirals for chronic HCV infection because the drugs are not very effective at clearing the infection, cause serious adverse effects such as "making patients feel sick during a prolonged treatment course," and are expensive, said Dr. Mitchell H. Katz.

Moreover, physicians are reluctant to recommend antivirals if patients already have severe liver damage, because they may not tolerate the adverse effects and "because it is unclear whether even if the virus is suppressed their clinical function would improve." Conversely, physicians are reluctant to recommend the drugs to healthier patients because they may have time to wait until better therapies become available.

"The critical issue going forward is whether the new drugs that have been released (e.g., hepatitis C protease inhibitors) or are likely to be approved soon (e.g., hepatitis C nucleotide polymerase inhibitor) can achieve sustained viral suppression in a high percentage of patients without serious adverse effects," Dr. Katz noted.

Dr. Katz is an internist and director of the Los Angeles County Department of Health Services. He is a deputy editor of JAMA. These remarks were taken from his Editor’s Note accompanying Dr. McCombs’ report (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12418]).

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Many patients and clinicians are "unenthusiastic" about antivirals for chronic HCV infection because the drugs are not very effective at clearing the infection, cause serious adverse effects such as "making patients feel sick during a prolonged treatment course," and are expensive, said Dr. Mitchell H. Katz.

Moreover, physicians are reluctant to recommend antivirals if patients already have severe liver damage, because they may not tolerate the adverse effects and "because it is unclear whether even if the virus is suppressed their clinical function would improve." Conversely, physicians are reluctant to recommend the drugs to healthier patients because they may have time to wait until better therapies become available.

"The critical issue going forward is whether the new drugs that have been released (e.g., hepatitis C protease inhibitors) or are likely to be approved soon (e.g., hepatitis C nucleotide polymerase inhibitor) can achieve sustained viral suppression in a high percentage of patients without serious adverse effects," Dr. Katz noted.

Dr. Katz is an internist and director of the Los Angeles County Department of Health Services. He is a deputy editor of JAMA. These remarks were taken from his Editor’s Note accompanying Dr. McCombs’ report (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12418]).

Body

Many patients and clinicians are "unenthusiastic" about antivirals for chronic HCV infection because the drugs are not very effective at clearing the infection, cause serious adverse effects such as "making patients feel sick during a prolonged treatment course," and are expensive, said Dr. Mitchell H. Katz.

Moreover, physicians are reluctant to recommend antivirals if patients already have severe liver damage, because they may not tolerate the adverse effects and "because it is unclear whether even if the virus is suppressed their clinical function would improve." Conversely, physicians are reluctant to recommend the drugs to healthier patients because they may have time to wait until better therapies become available.

"The critical issue going forward is whether the new drugs that have been released (e.g., hepatitis C protease inhibitors) or are likely to be approved soon (e.g., hepatitis C nucleotide polymerase inhibitor) can achieve sustained viral suppression in a high percentage of patients without serious adverse effects," Dr. Katz noted.

Dr. Katz is an internist and director of the Los Angeles County Department of Health Services. He is a deputy editor of JAMA. These remarks were taken from his Editor’s Note accompanying Dr. McCombs’ report (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12418]).

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Clinicians, patients don’t want antivirals
Clinicians, patients don’t want antivirals

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

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Undetectable viral load cut HCV morbidity, mortality
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FROM THE LIVER MEETING 2013

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Major Finding: Patients with chronic hepatitis C viral infection who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint of new-onset cirrhosis, hepatocellular carcinoma, or a liver-related hospitalization.

Data Source: An analysis of Veterans Affairs clinical data concerning 128,769 adults with chronic HCV infection who were followed for 6 years, of whom 16.4% achieved an undetectable viral load.

Disclosures: Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.