Kari Oakes

Clinicians may soon have a wider array of medicines that achieve effective pain management for those with legitimate need, but that also address the current public health crisis of prescription opioid diversion and abuse.

The FDA is leading that effort with its newly available document guiding industry in the evaluation and labeling of abuse-deterrent opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs for the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, announced in a telebriefing held on April 1.

Entitled “Abuse-Deterrent Opioids – Evaluation and Labeling,” this FDA document provides guidance and recommendations for the pharmacy industry. While the document does not have immediate impact on prescribing practices, prescribers can expect to see development of a wider array of products using a variety of strategies to deter abuse, thanks to the clarification provided by this document and the expedited review of abuse-deterrent opioid formulations offered by the FDA.

A particular area of interest has been novel naloxone-containing opioids. Naloxone, an opioid receptor antagonist, quickly and powerfully reverses the effect of opioids and is particularly effective at reversing respiratory depression, a common proximate cause of death in opioid overdose.

Other chemical or physical formulations, the inclusion of aversive substances, and the use of abuse-resistant delivery systems are strategies encouraged by the draft document.

Ensuring the availability of more opioids with abuse-deterrent formulations is an important public health measure to stem opioid abuse, and the FDA is but one of several federal agencies working on this problem. The guidance document was issued to provide industry with the FDA’s current thinking regarding the studies that should be conducted, how drugs should be evaluated, and what labeling claims may be approved, said Dr. Throckmorton.

The FDA is focused on supporting the development of these medications to balance the need of those in pain while reducing abuse. To that end, applicants can also expect an expedited review process. “Tackling the opioid epidemic is a high priority for the FDA,” noted Dr. Throckmorton.

Further guidance regarding generic opioids with abuse-deterrent properties is expected soon. Dr. Sharon Hertz, acting director of CDER’s Division of Anesthesia, Analgesia, and Addiction Products, noted that current FDA and state laws still govern substitutability of generic opioids.

Today’s telebriefing caps off a period of brisk activity. An October 2014 public meeting regarding a draft guidance document was followed by a public comment period. To date, the FDA has met with more than 30 manufacturers interested in producing abuse-deterrent opioid formulations, noted Dr. Throckmorton.

Clinicians may soon have a wider array of medicines that achieve effective pain management for those with legitimate need, but that also address the current public health crisis of prescription opioid diversion and abuse.

The FDA is leading that effort with its newly available document guiding industry in the evaluation and labeling of abuse-deterrent opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs for the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, announced in a telebriefing held on April 1.

Entitled “Abuse-Deterrent Opioids – Evaluation and Labeling,” this FDA document provides guidance and recommendations for the pharmacy industry. While the document does not have immediate impact on prescribing practices, prescribers can expect to see development of a wider array of products using a variety of strategies to deter abuse, thanks to the clarification provided by this document and the expedited review of abuse-deterrent opioid formulations offered by the FDA.

A particular area of interest has been novel naloxone-containing opioids. Naloxone, an opioid receptor antagonist, quickly and powerfully reverses the effect of opioids and is particularly effective at reversing respiratory depression, a common proximate cause of death in opioid overdose.

Other chemical or physical formulations, the inclusion of aversive substances, and the use of abuse-resistant delivery systems are strategies encouraged by the draft document.

Ensuring the availability of more opioids with abuse-deterrent formulations is an important public health measure to stem opioid abuse, and the FDA is but one of several federal agencies working on this problem. The guidance document was issued to provide industry with the FDA’s current thinking regarding the studies that should be conducted, how drugs should be evaluated, and what labeling claims may be approved, said Dr. Throckmorton.

The FDA is focused on supporting the development of these medications to balance the need of those in pain while reducing abuse. To that end, applicants can also expect an expedited review process. “Tackling the opioid epidemic is a high priority for the FDA,” noted Dr. Throckmorton.

Further guidance regarding generic opioids with abuse-deterrent properties is expected soon. Dr. Sharon Hertz, acting director of CDER’s Division of Anesthesia, Analgesia, and Addiction Products, noted that current FDA and state laws still govern substitutability of generic opioids.

Today’s telebriefing caps off a period of brisk activity. An October 2014 public meeting regarding a draft guidance document was followed by a public comment period. To date, the FDA has met with more than 30 manufacturers interested in producing abuse-deterrent opioid formulations, noted Dr. Throckmorton.

Clinicians may soon have a wider array of medicines that achieve effective pain management for those with legitimate need, but that also address the current public health crisis of prescription opioid diversion and abuse.

The FDA is leading that effort with its newly available document guiding industry in the evaluation and labeling of abuse-deterrent opioids, Dr. Douglas Throckmorton, deputy director of regulatory programs for the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, announced in a telebriefing held on April 1.

Entitled “Abuse-Deterrent Opioids – Evaluation and Labeling,” this FDA document provides guidance and recommendations for the pharmacy industry. While the document does not have immediate impact on prescribing practices, prescribers can expect to see development of a wider array of products using a variety of strategies to deter abuse, thanks to the clarification provided by this document and the expedited review of abuse-deterrent opioid formulations offered by the FDA.

A particular area of interest has been novel naloxone-containing opioids. Naloxone, an opioid receptor antagonist, quickly and powerfully reverses the effect of opioids and is particularly effective at reversing respiratory depression, a common proximate cause of death in opioid overdose.

Other chemical or physical formulations, the inclusion of aversive substances, and the use of abuse-resistant delivery systems are strategies encouraged by the draft document.

Ensuring the availability of more opioids with abuse-deterrent formulations is an important public health measure to stem opioid abuse, and the FDA is but one of several federal agencies working on this problem. The guidance document was issued to provide industry with the FDA’s current thinking regarding the studies that should be conducted, how drugs should be evaluated, and what labeling claims may be approved, said Dr. Throckmorton.

The FDA is focused on supporting the development of these medications to balance the need of those in pain while reducing abuse. To that end, applicants can also expect an expedited review process. “Tackling the opioid epidemic is a high priority for the FDA,” noted Dr. Throckmorton.

Further guidance regarding generic opioids with abuse-deterrent properties is expected soon. Dr. Sharon Hertz, acting director of CDER’s Division of Anesthesia, Analgesia, and Addiction Products, noted that current FDA and state laws still govern substitutability of generic opioids.

Today’s telebriefing caps off a period of brisk activity. An October 2014 public meeting regarding a draft guidance document was followed by a public comment period. To date, the FDA has met with more than 30 manufacturers interested in producing abuse-deterrent opioid formulations, noted Dr. Throckmorton.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

AGA Note
Review the AGA Hepatitis C Clinical Service Line to learn more about managing the disease. 

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

AGA Note
Review the AGA Hepatitis C Clinical Service Line to learn more about managing the disease. 

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

AGA Note
Review the AGA Hepatitis C Clinical Service Line to learn more about managing the disease. 

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For Medicare beneficiaries with rheumatoid arthritis, out-of-pocket costs are closely linked to whether a patient is more likely to receive facility- or home-administered biologic treatment, according to a retrospective analysis of how patient cost sharing affects utilization and spending patterns.

Medicare Part D beneficiaries with rheumatoid arthritis (RA) who receive a low-income subsidy (LIS) are more likely to receive biologic medication that can be self-injected at home, the study found, while those without subsidies face greater out-of-pocket costs for outpatient medications and are more likely to receive facility-administered drugs. Lead study author Dr. Jinoos Yazdany noted, “Our findings shed light on the complexity of current Medicare drug coverage policies for biologic DMARDs.”

Dr. Yazdany and her associates at the University of California, San Francisco, used 2009 Medicare claims to obtain a random nationwide sample of 5% of all Medicare beneficiaries with RA who were dispensed at least one RA medication. Of the 6,932 beneficiaries identified, 1,812 (26.1%) were dispensed a biologic disease-modifying antirheumatic drug (DMARD). Utilization patterns of the remainder, who received a nonbiologic DMARD, were used for comparison. In 2009, the biologic DMARDs infliximab, abatacept, and rituximab were all facility-administered medications reimbursable under Medicare Part B, while etanercept, adalimumab, and anakinra were available for home self-injection and were therefore Part D drugs (Arthritis Care Res. 2015 March 16 [doi:10.1002/acr.22580]).

Examining biologic DMARD use and costs, the study calculated costs to Medicare for both home- and facility-administered medications. Part D dispensing data were used to calculate costs to patients by determining the actual out-of-pocket dollar costs for beneficiaries. This information was not available for Part B events, so investigators used a range from 0%-20% cost-sharing to estimate patient costs.

Patient costs for Medicare Part D were further divided by LIS status, since LIS confers minimal cost sharing for outpatient drugs. By contrast, nonsubsidized Part D recipients incur variable costs; the current Medicare Part D coverage gap – also known as the doughnut hole – means that up to 100% of the cost of medications may be borne by the patient at certain points in the coverage cycle.

Multinomial regression analysis showed that those receiving a facility-administered biologic DMARD under Part B were significantly less likely than those receiving nonbiologic DMARDs to have a LIS (relative risk, 0.58; 95% confidence interval, 0.48-0.69). Recipients of self-injected DMARDs under Part D, in contrast, were much more likely to have a LIS than were those in the nonbiologic DMARD group (RR, 2.98; 95% CI, 2.50-3.56). Annual Part D out-of-pocket costs for those receiving biologics with no LIS were a mean $3,751, compared with a mean $72 for the LIS Part D group. However, beneficiaries with no LIS paid a maximum of $2,584 out of pocket for biologic DMARDs through Part B (assuming 20% supplemental insurance coverage).

Since the Affordable Care Act will reform Part D to help close the coverage gap, the study also projected how ACA reform, once adopted, would affect cost sharing and use patterns. Dr. Yazdany and her colleagues projected out-of-pocket biologic DMARD costs into full reform implementation in the year 2020, calculating that nonsubsidized out-of-pocket expenses would still be $2,588. The authors noted that “patient cost sharing is an important determinant of drug choice in Medicare’s part B versus part D programs ... the current system risks significant financial burden to many patients.”

When asked to comment on the study, Kaleb Michaud, Ph.D., assistant professor of rheumatology at the University of Nebraska Medical Center, Omaha, and codirector of the National Data Bank for Rheumatic Diseases, noted that this well-constructed study made very good use of Medicare data to point to a fundamental problem with reimbursement for rheumatic disease medications. “Rather than asking, ‘What’s the best drug for this patient?’ we find ourselves asking, ‘What drug can this patient afford?’ ” he said.

The study was funded by the National Institutes of Health, a Research Allocation and Evaluation Award from the University of California, San Francisco, and the Rosaline Russell Medical Research Center for Arthritis. The authors reported that they had no conflicts of interest.

For Medicare beneficiaries with rheumatoid arthritis, out-of-pocket costs are closely linked to whether a patient is more likely to receive facility- or home-administered biologic treatment, according to a retrospective analysis of how patient cost sharing affects utilization and spending patterns.

Medicare Part D beneficiaries with rheumatoid arthritis (RA) who receive a low-income subsidy (LIS) are more likely to receive biologic medication that can be self-injected at home, the study found, while those without subsidies face greater out-of-pocket costs for outpatient medications and are more likely to receive facility-administered drugs. Lead study author Dr. Jinoos Yazdany noted, “Our findings shed light on the complexity of current Medicare drug coverage policies for biologic DMARDs.”

Dr. Yazdany and her associates at the University of California, San Francisco, used 2009 Medicare claims to obtain a random nationwide sample of 5% of all Medicare beneficiaries with RA who were dispensed at least one RA medication. Of the 6,932 beneficiaries identified, 1,812 (26.1%) were dispensed a biologic disease-modifying antirheumatic drug (DMARD). Utilization patterns of the remainder, who received a nonbiologic DMARD, were used for comparison. In 2009, the biologic DMARDs infliximab, abatacept, and rituximab were all facility-administered medications reimbursable under Medicare Part B, while etanercept, adalimumab, and anakinra were available for home self-injection and were therefore Part D drugs (Arthritis Care Res. 2015 March 16 [doi:10.1002/acr.22580]).

Examining biologic DMARD use and costs, the study calculated costs to Medicare for both home- and facility-administered medications. Part D dispensing data were used to calculate costs to patients by determining the actual out-of-pocket dollar costs for beneficiaries. This information was not available for Part B events, so investigators used a range from 0%-20% cost-sharing to estimate patient costs.

Patient costs for Medicare Part D were further divided by LIS status, since LIS confers minimal cost sharing for outpatient drugs. By contrast, nonsubsidized Part D recipients incur variable costs; the current Medicare Part D coverage gap – also known as the doughnut hole – means that up to 100% of the cost of medications may be borne by the patient at certain points in the coverage cycle.

Multinomial regression analysis showed that those receiving a facility-administered biologic DMARD under Part B were significantly less likely than those receiving nonbiologic DMARDs to have a LIS (relative risk, 0.58; 95% confidence interval, 0.48-0.69). Recipients of self-injected DMARDs under Part D, in contrast, were much more likely to have a LIS than were those in the nonbiologic DMARD group (RR, 2.98; 95% CI, 2.50-3.56). Annual Part D out-of-pocket costs for those receiving biologics with no LIS were a mean $3,751, compared with a mean $72 for the LIS Part D group. However, beneficiaries with no LIS paid a maximum of $2,584 out of pocket for biologic DMARDs through Part B (assuming 20% supplemental insurance coverage).

Since the Affordable Care Act will reform Part D to help close the coverage gap, the study also projected how ACA reform, once adopted, would affect cost sharing and use patterns. Dr. Yazdany and her colleagues projected out-of-pocket biologic DMARD costs into full reform implementation in the year 2020, calculating that nonsubsidized out-of-pocket expenses would still be $2,588. The authors noted that “patient cost sharing is an important determinant of drug choice in Medicare’s part B versus part D programs ... the current system risks significant financial burden to many patients.”

When asked to comment on the study, Kaleb Michaud, Ph.D., assistant professor of rheumatology at the University of Nebraska Medical Center, Omaha, and codirector of the National Data Bank for Rheumatic Diseases, noted that this well-constructed study made very good use of Medicare data to point to a fundamental problem with reimbursement for rheumatic disease medications. “Rather than asking, ‘What’s the best drug for this patient?’ we find ourselves asking, ‘What drug can this patient afford?’ ” he said.

The study was funded by the National Institutes of Health, a Research Allocation and Evaluation Award from the University of California, San Francisco, and the Rosaline Russell Medical Research Center for Arthritis. The authors reported that they had no conflicts of interest.

For Medicare beneficiaries with rheumatoid arthritis, out-of-pocket costs are closely linked to whether a patient is more likely to receive facility- or home-administered biologic treatment, according to a retrospective analysis of how patient cost sharing affects utilization and spending patterns.

Medicare Part D beneficiaries with rheumatoid arthritis (RA) who receive a low-income subsidy (LIS) are more likely to receive biologic medication that can be self-injected at home, the study found, while those without subsidies face greater out-of-pocket costs for outpatient medications and are more likely to receive facility-administered drugs. Lead study author Dr. Jinoos Yazdany noted, “Our findings shed light on the complexity of current Medicare drug coverage policies for biologic DMARDs.”

Dr. Yazdany and her associates at the University of California, San Francisco, used 2009 Medicare claims to obtain a random nationwide sample of 5% of all Medicare beneficiaries with RA who were dispensed at least one RA medication. Of the 6,932 beneficiaries identified, 1,812 (26.1%) were dispensed a biologic disease-modifying antirheumatic drug (DMARD). Utilization patterns of the remainder, who received a nonbiologic DMARD, were used for comparison. In 2009, the biologic DMARDs infliximab, abatacept, and rituximab were all facility-administered medications reimbursable under Medicare Part B, while etanercept, adalimumab, and anakinra were available for home self-injection and were therefore Part D drugs (Arthritis Care Res. 2015 March 16 [doi:10.1002/acr.22580]).

Examining biologic DMARD use and costs, the study calculated costs to Medicare for both home- and facility-administered medications. Part D dispensing data were used to calculate costs to patients by determining the actual out-of-pocket dollar costs for beneficiaries. This information was not available for Part B events, so investigators used a range from 0%-20% cost-sharing to estimate patient costs.

Patient costs for Medicare Part D were further divided by LIS status, since LIS confers minimal cost sharing for outpatient drugs. By contrast, nonsubsidized Part D recipients incur variable costs; the current Medicare Part D coverage gap – also known as the doughnut hole – means that up to 100% of the cost of medications may be borne by the patient at certain points in the coverage cycle.

Multinomial regression analysis showed that those receiving a facility-administered biologic DMARD under Part B were significantly less likely than those receiving nonbiologic DMARDs to have a LIS (relative risk, 0.58; 95% confidence interval, 0.48-0.69). Recipients of self-injected DMARDs under Part D, in contrast, were much more likely to have a LIS than were those in the nonbiologic DMARD group (RR, 2.98; 95% CI, 2.50-3.56). Annual Part D out-of-pocket costs for those receiving biologics with no LIS were a mean $3,751, compared with a mean $72 for the LIS Part D group. However, beneficiaries with no LIS paid a maximum of $2,584 out of pocket for biologic DMARDs through Part B (assuming 20% supplemental insurance coverage).

Since the Affordable Care Act will reform Part D to help close the coverage gap, the study also projected how ACA reform, once adopted, would affect cost sharing and use patterns. Dr. Yazdany and her colleagues projected out-of-pocket biologic DMARD costs into full reform implementation in the year 2020, calculating that nonsubsidized out-of-pocket expenses would still be $2,588. The authors noted that “patient cost sharing is an important determinant of drug choice in Medicare’s part B versus part D programs ... the current system risks significant financial burden to many patients.”

When asked to comment on the study, Kaleb Michaud, Ph.D., assistant professor of rheumatology at the University of Nebraska Medical Center, Omaha, and codirector of the National Data Bank for Rheumatic Diseases, noted that this well-constructed study made very good use of Medicare data to point to a fundamental problem with reimbursement for rheumatic disease medications. “Rather than asking, ‘What’s the best drug for this patient?’ we find ourselves asking, ‘What drug can this patient afford?’ ” he said.

The study was funded by the National Institutes of Health, a Research Allocation and Evaluation Award from the University of California, San Francisco, and the Rosaline Russell Medical Research Center for Arthritis. The authors reported that they had no conflicts of interest.

BALTIMORE – Distinct patterns of blood pressure changes in midlife are associated with varying degrees of risk for cardiovascular disease and death, according to a multisite study.

These patterns of change contributed to risk for both CVD and mortality, separate from the known association of absolute elevation of systolic blood pressure with CVD and death. Natalia Petruski-Ivleva of the University of North Carolina, Chapel Hill, and colleagues identified SBP patterns emerging from the biracial, multisite Atherosclerosis Risk in Communities (ARIC) study and presented the results at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

The study included 9,882 patients from the ARIC population who had recorded BPs at four study visits between 1987 and 1998, and whose outcomes were tracked over the period from 1987 to 2011. Median follow-up after the last study visit was 13.2 years. Participants were grouped by patterns of change in SBP over time using a latent class growth model; this analytic model allowed for the discovery of similar groups of cases within the data.

Results were adjusted for age and demographic characteristics, as well as for self-reported hypertension medication use. In addition to all-cause mortality, outcomes included coronary heart disease, heart failure, and stroke.

In all, six distinct patterns emerged of change in SBP over the study visit period, with three groups having SBPs consistently below the threshold of 140 mm Hg, and three other groups showing varying patterns of elevation. About 84% of participants fell into one of the three groups that showed parallel patterns of SBP change, with pressures slowly rising over time, but never exceeding 140 mm Hg. The remainder of participants were grouped into three other patterns. One showed a steep increase over time from an initial SBP just under 140 mm Hg to a final reading just over 160 mm Hg; a second showed high and sustained SBPs of more than 160 mm Hg at all study visits. Finally, some participants had initially elevated SBPs that fell to the normal range by the end of the study.

Overall, analysis showed a gradient of risk, with lower SBP associated with lower risk of CVD and death. This was true even for those participants in the first three groups, whose SBPs stayed below 140 mm Hg throughout. Notably, the pattern of steep increase of already elevated SBP, as well as that of sustained elevated blood pressures, were both associated with the highest all-cause mortality. Reducing SBP to less than 140 mm Hg was not associated with reduced risk of CHD in the final group.

The three higher-risk groups were more likely to be obese, black, on hypertension medication, and have diabetes. They were also older on average than participants with the three nonelevated patterns.

These patterns of change, said Ms. Petruski-Ivleva, “contribute varying amounts of risk of CVD and mortality in addition to the risk imparted by the absolute SBP level.” Though the clinical significance of these patterns of blood pressure change needs more examination, she said that the results underscore the cumulative impact of elevated SBP through midlife.

BALTIMORE – Distinct patterns of blood pressure changes in midlife are associated with varying degrees of risk for cardiovascular disease and death, according to a multisite study.

These patterns of change contributed to risk for both CVD and mortality, separate from the known association of absolute elevation of systolic blood pressure with CVD and death. Natalia Petruski-Ivleva of the University of North Carolina, Chapel Hill, and colleagues identified SBP patterns emerging from the biracial, multisite Atherosclerosis Risk in Communities (ARIC) study and presented the results at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

The study included 9,882 patients from the ARIC population who had recorded BPs at four study visits between 1987 and 1998, and whose outcomes were tracked over the period from 1987 to 2011. Median follow-up after the last study visit was 13.2 years. Participants were grouped by patterns of change in SBP over time using a latent class growth model; this analytic model allowed for the discovery of similar groups of cases within the data.

Results were adjusted for age and demographic characteristics, as well as for self-reported hypertension medication use. In addition to all-cause mortality, outcomes included coronary heart disease, heart failure, and stroke.

In all, six distinct patterns emerged of change in SBP over the study visit period, with three groups having SBPs consistently below the threshold of 140 mm Hg, and three other groups showing varying patterns of elevation. About 84% of participants fell into one of the three groups that showed parallel patterns of SBP change, with pressures slowly rising over time, but never exceeding 140 mm Hg. The remainder of participants were grouped into three other patterns. One showed a steep increase over time from an initial SBP just under 140 mm Hg to a final reading just over 160 mm Hg; a second showed high and sustained SBPs of more than 160 mm Hg at all study visits. Finally, some participants had initially elevated SBPs that fell to the normal range by the end of the study.

Overall, analysis showed a gradient of risk, with lower SBP associated with lower risk of CVD and death. This was true even for those participants in the first three groups, whose SBPs stayed below 140 mm Hg throughout. Notably, the pattern of steep increase of already elevated SBP, as well as that of sustained elevated blood pressures, were both associated with the highest all-cause mortality. Reducing SBP to less than 140 mm Hg was not associated with reduced risk of CHD in the final group.

The three higher-risk groups were more likely to be obese, black, on hypertension medication, and have diabetes. They were also older on average than participants with the three nonelevated patterns.

These patterns of change, said Ms. Petruski-Ivleva, “contribute varying amounts of risk of CVD and mortality in addition to the risk imparted by the absolute SBP level.” Though the clinical significance of these patterns of blood pressure change needs more examination, she said that the results underscore the cumulative impact of elevated SBP through midlife.

BALTIMORE – Distinct patterns of blood pressure changes in midlife are associated with varying degrees of risk for cardiovascular disease and death, according to a multisite study.

These patterns of change contributed to risk for both CVD and mortality, separate from the known association of absolute elevation of systolic blood pressure with CVD and death. Natalia Petruski-Ivleva of the University of North Carolina, Chapel Hill, and colleagues identified SBP patterns emerging from the biracial, multisite Atherosclerosis Risk in Communities (ARIC) study and presented the results at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

The study included 9,882 patients from the ARIC population who had recorded BPs at four study visits between 1987 and 1998, and whose outcomes were tracked over the period from 1987 to 2011. Median follow-up after the last study visit was 13.2 years. Participants were grouped by patterns of change in SBP over time using a latent class growth model; this analytic model allowed for the discovery of similar groups of cases within the data.

Results were adjusted for age and demographic characteristics, as well as for self-reported hypertension medication use. In addition to all-cause mortality, outcomes included coronary heart disease, heart failure, and stroke.

In all, six distinct patterns emerged of change in SBP over the study visit period, with three groups having SBPs consistently below the threshold of 140 mm Hg, and three other groups showing varying patterns of elevation. About 84% of participants fell into one of the three groups that showed parallel patterns of SBP change, with pressures slowly rising over time, but never exceeding 140 mm Hg. The remainder of participants were grouped into three other patterns. One showed a steep increase over time from an initial SBP just under 140 mm Hg to a final reading just over 160 mm Hg; a second showed high and sustained SBPs of more than 160 mm Hg at all study visits. Finally, some participants had initially elevated SBPs that fell to the normal range by the end of the study.

Overall, analysis showed a gradient of risk, with lower SBP associated with lower risk of CVD and death. This was true even for those participants in the first three groups, whose SBPs stayed below 140 mm Hg throughout. Notably, the pattern of steep increase of already elevated SBP, as well as that of sustained elevated blood pressures, were both associated with the highest all-cause mortality. Reducing SBP to less than 140 mm Hg was not associated with reduced risk of CHD in the final group.

The three higher-risk groups were more likely to be obese, black, on hypertension medication, and have diabetes. They were also older on average than participants with the three nonelevated patterns.

These patterns of change, said Ms. Petruski-Ivleva, “contribute varying amounts of risk of CVD and mortality in addition to the risk imparted by the absolute SBP level.” Though the clinical significance of these patterns of blood pressure change needs more examination, she said that the results underscore the cumulative impact of elevated SBP through midlife.

For patients with nonalcoholic steatohepatitis (NASH), a bile acid derivative that acts on a nuclear receptor reduced liver fat and fibrosis, but patients taking the drug also had worsening in serum lipid values and increased insulin resistance.

The lipophilic bile acid obeticholic acid showed promise in the FLINT trial (Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment) for NASH patients whose liver disease improved but did not resolve.

Dr. Brent Neuschwander-Tetri of Saint Louis University, and coinvestigators in the National Institute of Diabetes and Digestive and Kidney Diseases’ NASH Clinical Research Network, conducted the multicenter, randomized, placebo-controlled study. The findings were published in the Lancet.

Obeticholic acid, a farnesoid X nuclear receptor agonist, works at a site whose activation promotes increased insulin sensitivity and decreased serum triglycerides. Serum lipids may also be improved by increased peripheral clearance of VLDL, increased reverse cholesterol transport, and reduced lipid synthesis in the liver. Currently, the only other treatments for NASH, aside from diet and lifestyle modifications, are thiazolidinediones and vitamin E. Long-term safety and efficacy of these medications are unknown, especially in NASH patients with diabetes (Lancet 2015;385:956-65 [doi:10.1016/S0140-6736(14)61933-4]).

Study participants were adults with biopsy-confirmed NASH or borderline NASH with histologic steatosis, ballooning, and lobular inflammation, but without cirrhosis. The study excluded heavy consumers of alcohol. Baseline and final assessments included liver biopsy and demographic and anthropometric information, as well as metabolic and lipid markers and liver enzymes.

FLINT’s primary outcome measure was improved liver histology, defined as a decrease of two or more points on a nonalcoholic fatty liver disease (NAFLD) pathology scoring system, without a worsening of liver fibrosis. Resolution of NASH was a secondary outcome, as were changes in liver enzymes, body measurements, and homeostasis model of assessment of insulin resistance (HOMA-IR) levels.

The study’s Data Safety Monitoring Board recommended stopping biopsies after about half the patients had received biopsies and the primary histologic outcome measure was met, in order to avoid unnecessary patient risk.

An intention-to-treat analysis found that 50 (45%) of 110 patients receiving obeticholic acid had improved liver histology, compared to 23 (21%) of 109 patients receiving placebo (relative risk 1.9, 95% CI 1.3-2.8, P = .0002). This difference did not change with prespecified subgroup analyses. Serum AST and ALT measures decreased significantly for the treatment group. The medication was generally well tolerated, though pruritis developed in 33 (23%) of 141 patients in the intervention group and 9 (6%) of the placebo group.

Total serum cholesterol and LDL cholesterol, however, increased for the obeticholic acid group, while HDL cholesterol decreased. Insulin resistance as measured by HOMA-IR increased slightly for the treatment group, an unexpected effect. Study authors noted that this class of medication’s effect on cholesterol transport is complex. “Future studies of farnesoid X nuclear receptor agonists,” they noted, “will need to address the consequences of these changes on cardiovascular outcomes.”

Dr. Neuschwander-Tetri disclosed ties with Genentech/Roche, Nimbus Discovery, Boehringer Ingelheim, and Bristol-Myers Squibb. Several coinvestigators disclosed ties with various companies, including Intercept Pharmaceuticals, which provided partial funding for the trial under a Collaborative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.

For patients with nonalcoholic steatohepatitis (NASH), a bile acid derivative that acts on a nuclear receptor reduced liver fat and fibrosis, but patients taking the drug also had worsening in serum lipid values and increased insulin resistance.

The lipophilic bile acid obeticholic acid showed promise in the FLINT trial (Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment) for NASH patients whose liver disease improved but did not resolve.

Dr. Brent Neuschwander-Tetri of Saint Louis University, and coinvestigators in the National Institute of Diabetes and Digestive and Kidney Diseases’ NASH Clinical Research Network, conducted the multicenter, randomized, placebo-controlled study. The findings were published in the Lancet.

Obeticholic acid, a farnesoid X nuclear receptor agonist, works at a site whose activation promotes increased insulin sensitivity and decreased serum triglycerides. Serum lipids may also be improved by increased peripheral clearance of VLDL, increased reverse cholesterol transport, and reduced lipid synthesis in the liver. Currently, the only other treatments for NASH, aside from diet and lifestyle modifications, are thiazolidinediones and vitamin E. Long-term safety and efficacy of these medications are unknown, especially in NASH patients with diabetes (Lancet 2015;385:956-65 [doi:10.1016/S0140-6736(14)61933-4]).

Study participants were adults with biopsy-confirmed NASH or borderline NASH with histologic steatosis, ballooning, and lobular inflammation, but without cirrhosis. The study excluded heavy consumers of alcohol. Baseline and final assessments included liver biopsy and demographic and anthropometric information, as well as metabolic and lipid markers and liver enzymes.

FLINT’s primary outcome measure was improved liver histology, defined as a decrease of two or more points on a nonalcoholic fatty liver disease (NAFLD) pathology scoring system, without a worsening of liver fibrosis. Resolution of NASH was a secondary outcome, as were changes in liver enzymes, body measurements, and homeostasis model of assessment of insulin resistance (HOMA-IR) levels.

The study’s Data Safety Monitoring Board recommended stopping biopsies after about half the patients had received biopsies and the primary histologic outcome measure was met, in order to avoid unnecessary patient risk.

An intention-to-treat analysis found that 50 (45%) of 110 patients receiving obeticholic acid had improved liver histology, compared to 23 (21%) of 109 patients receiving placebo (relative risk 1.9, 95% CI 1.3-2.8, P = .0002). This difference did not change with prespecified subgroup analyses. Serum AST and ALT measures decreased significantly for the treatment group. The medication was generally well tolerated, though pruritis developed in 33 (23%) of 141 patients in the intervention group and 9 (6%) of the placebo group.

Total serum cholesterol and LDL cholesterol, however, increased for the obeticholic acid group, while HDL cholesterol decreased. Insulin resistance as measured by HOMA-IR increased slightly for the treatment group, an unexpected effect. Study authors noted that this class of medication’s effect on cholesterol transport is complex. “Future studies of farnesoid X nuclear receptor agonists,” they noted, “will need to address the consequences of these changes on cardiovascular outcomes.”

Dr. Neuschwander-Tetri disclosed ties with Genentech/Roche, Nimbus Discovery, Boehringer Ingelheim, and Bristol-Myers Squibb. Several coinvestigators disclosed ties with various companies, including Intercept Pharmaceuticals, which provided partial funding for the trial under a Collaborative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.

For patients with nonalcoholic steatohepatitis (NASH), a bile acid derivative that acts on a nuclear receptor reduced liver fat and fibrosis, but patients taking the drug also had worsening in serum lipid values and increased insulin resistance.

The lipophilic bile acid obeticholic acid showed promise in the FLINT trial (Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment) for NASH patients whose liver disease improved but did not resolve.

Dr. Brent Neuschwander-Tetri of Saint Louis University, and coinvestigators in the National Institute of Diabetes and Digestive and Kidney Diseases’ NASH Clinical Research Network, conducted the multicenter, randomized, placebo-controlled study. The findings were published in the Lancet.

Obeticholic acid, a farnesoid X nuclear receptor agonist, works at a site whose activation promotes increased insulin sensitivity and decreased serum triglycerides. Serum lipids may also be improved by increased peripheral clearance of VLDL, increased reverse cholesterol transport, and reduced lipid synthesis in the liver. Currently, the only other treatments for NASH, aside from diet and lifestyle modifications, are thiazolidinediones and vitamin E. Long-term safety and efficacy of these medications are unknown, especially in NASH patients with diabetes (Lancet 2015;385:956-65 [doi:10.1016/S0140-6736(14)61933-4]).

Study participants were adults with biopsy-confirmed NASH or borderline NASH with histologic steatosis, ballooning, and lobular inflammation, but without cirrhosis. The study excluded heavy consumers of alcohol. Baseline and final assessments included liver biopsy and demographic and anthropometric information, as well as metabolic and lipid markers and liver enzymes.

FLINT’s primary outcome measure was improved liver histology, defined as a decrease of two or more points on a nonalcoholic fatty liver disease (NAFLD) pathology scoring system, without a worsening of liver fibrosis. Resolution of NASH was a secondary outcome, as were changes in liver enzymes, body measurements, and homeostasis model of assessment of insulin resistance (HOMA-IR) levels.

The study’s Data Safety Monitoring Board recommended stopping biopsies after about half the patients had received biopsies and the primary histologic outcome measure was met, in order to avoid unnecessary patient risk.

An intention-to-treat analysis found that 50 (45%) of 110 patients receiving obeticholic acid had improved liver histology, compared to 23 (21%) of 109 patients receiving placebo (relative risk 1.9, 95% CI 1.3-2.8, P = .0002). This difference did not change with prespecified subgroup analyses. Serum AST and ALT measures decreased significantly for the treatment group. The medication was generally well tolerated, though pruritis developed in 33 (23%) of 141 patients in the intervention group and 9 (6%) of the placebo group.

Total serum cholesterol and LDL cholesterol, however, increased for the obeticholic acid group, while HDL cholesterol decreased. Insulin resistance as measured by HOMA-IR increased slightly for the treatment group, an unexpected effect. Study authors noted that this class of medication’s effect on cholesterol transport is complex. “Future studies of farnesoid X nuclear receptor agonists,” they noted, “will need to address the consequences of these changes on cardiovascular outcomes.”

Dr. Neuschwander-Tetri disclosed ties with Genentech/Roche, Nimbus Discovery, Boehringer Ingelheim, and Bristol-Myers Squibb. Several coinvestigators disclosed ties with various companies, including Intercept Pharmaceuticals, which provided partial funding for the trial under a Collaborative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.