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Cabozantinib bests sunitinib against metastatic RCC
Cabozantinib showed significant improvements in progression-free survival and objective response rate over standard-of-care sunitinib in a phase II clinical trial of adults with metastatic renal cell carcinoma, according to a report published in the Journal of Clinical Oncology.
As a first-line therapy for patients with poor- to intermediate-risk renal cell carcinoma (RCC), cabozantinib improved progression-free survival by approximately 3 months, corresponding to a 34% reduction in the rate of disease progression or death. This is the first study in this patient population in which another agent demonstrated “notable and clinically meaningful” superiority over sunitinib, which has been an established standard of care for more than 10 years, wrote Toni K. Choueiri, MD, director of the Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, and his associates.
In the open-label study, participants were randomly assigned to receive daily oral cabozantinib (79 patients) or daily oral sunitinib (78 patients) in 6-week cycles until disease progressed, intolerance developed, or patients withdrew from treatment. A total of 36% had bone metastases at baseline, an indicator of poor prognosis.
The primary endpoint – median duration of progression-free survival or time to death from any cause – was 8.2 months with cabozantinib and 5.6 months with sunitinib (adjusted hazard ratio, 0.66). Analyses of patient subgroups defined by disease severity consistently favored cabozantinib. Reductions in target lesion size, as measured by CT or MRI, were observed in 87% of the cabozantinib group, compared with 44% of the sunitinib group, the investigators reported (J Clin Oncol. 2016 Nov 14. doi: 10.1200/JCO.2016.70.7398).
Preliminary data showed that overall survival was 30.3 months with cabozantinib and 21.8 months with sunitinib. This represents a 20% decrease in mortality with cabozantinib.
The median number of treatment cycles was greater in the cabozantinib group (five cycles) than in the sunitinib group (two cycles), and corresponded to median treatment durations of 6.9 months and 2.8 months, respectively. Rates of treatment discontinuation due to adverse events were similar between the two study groups, as were the rates of adverse events of any grade, adverse events of grade 3 or 4, and adverse events of grade 5.
These findings indicate that cabozantinib may represent a new treatment option for previously untreated poor- or intermediate-risk metastatic RCC, Dr. Choueiri and his associates wrote.
The study was supported by the National Institutes of Health and Exelixis, which provided the cabozantinib. Dr. Choueiri and many of his associates reported ties to numerous industry sources.
Cabozantinib showed significant improvements in progression-free survival and objective response rate over standard-of-care sunitinib in a phase II clinical trial of adults with metastatic renal cell carcinoma, according to a report published in the Journal of Clinical Oncology.
As a first-line therapy for patients with poor- to intermediate-risk renal cell carcinoma (RCC), cabozantinib improved progression-free survival by approximately 3 months, corresponding to a 34% reduction in the rate of disease progression or death. This is the first study in this patient population in which another agent demonstrated “notable and clinically meaningful” superiority over sunitinib, which has been an established standard of care for more than 10 years, wrote Toni K. Choueiri, MD, director of the Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, and his associates.
In the open-label study, participants were randomly assigned to receive daily oral cabozantinib (79 patients) or daily oral sunitinib (78 patients) in 6-week cycles until disease progressed, intolerance developed, or patients withdrew from treatment. A total of 36% had bone metastases at baseline, an indicator of poor prognosis.
The primary endpoint – median duration of progression-free survival or time to death from any cause – was 8.2 months with cabozantinib and 5.6 months with sunitinib (adjusted hazard ratio, 0.66). Analyses of patient subgroups defined by disease severity consistently favored cabozantinib. Reductions in target lesion size, as measured by CT or MRI, were observed in 87% of the cabozantinib group, compared with 44% of the sunitinib group, the investigators reported (J Clin Oncol. 2016 Nov 14. doi: 10.1200/JCO.2016.70.7398).
Preliminary data showed that overall survival was 30.3 months with cabozantinib and 21.8 months with sunitinib. This represents a 20% decrease in mortality with cabozantinib.
The median number of treatment cycles was greater in the cabozantinib group (five cycles) than in the sunitinib group (two cycles), and corresponded to median treatment durations of 6.9 months and 2.8 months, respectively. Rates of treatment discontinuation due to adverse events were similar between the two study groups, as were the rates of adverse events of any grade, adverse events of grade 3 or 4, and adverse events of grade 5.
These findings indicate that cabozantinib may represent a new treatment option for previously untreated poor- or intermediate-risk metastatic RCC, Dr. Choueiri and his associates wrote.
The study was supported by the National Institutes of Health and Exelixis, which provided the cabozantinib. Dr. Choueiri and many of his associates reported ties to numerous industry sources.
Cabozantinib showed significant improvements in progression-free survival and objective response rate over standard-of-care sunitinib in a phase II clinical trial of adults with metastatic renal cell carcinoma, according to a report published in the Journal of Clinical Oncology.
As a first-line therapy for patients with poor- to intermediate-risk renal cell carcinoma (RCC), cabozantinib improved progression-free survival by approximately 3 months, corresponding to a 34% reduction in the rate of disease progression or death. This is the first study in this patient population in which another agent demonstrated “notable and clinically meaningful” superiority over sunitinib, which has been an established standard of care for more than 10 years, wrote Toni K. Choueiri, MD, director of the Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, and his associates.
In the open-label study, participants were randomly assigned to receive daily oral cabozantinib (79 patients) or daily oral sunitinib (78 patients) in 6-week cycles until disease progressed, intolerance developed, or patients withdrew from treatment. A total of 36% had bone metastases at baseline, an indicator of poor prognosis.
The primary endpoint – median duration of progression-free survival or time to death from any cause – was 8.2 months with cabozantinib and 5.6 months with sunitinib (adjusted hazard ratio, 0.66). Analyses of patient subgroups defined by disease severity consistently favored cabozantinib. Reductions in target lesion size, as measured by CT or MRI, were observed in 87% of the cabozantinib group, compared with 44% of the sunitinib group, the investigators reported (J Clin Oncol. 2016 Nov 14. doi: 10.1200/JCO.2016.70.7398).
Preliminary data showed that overall survival was 30.3 months with cabozantinib and 21.8 months with sunitinib. This represents a 20% decrease in mortality with cabozantinib.
The median number of treatment cycles was greater in the cabozantinib group (five cycles) than in the sunitinib group (two cycles), and corresponded to median treatment durations of 6.9 months and 2.8 months, respectively. Rates of treatment discontinuation due to adverse events were similar between the two study groups, as were the rates of adverse events of any grade, adverse events of grade 3 or 4, and adverse events of grade 5.
These findings indicate that cabozantinib may represent a new treatment option for previously untreated poor- or intermediate-risk metastatic RCC, Dr. Choueiri and his associates wrote.
The study was supported by the National Institutes of Health and Exelixis, which provided the cabozantinib. Dr. Choueiri and many of his associates reported ties to numerous industry sources.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: The primary end point – median duration of progression-free survival or time to death from any cause – was 8.2 months with cabozantinib and 5.6 months with sunitinib (adjusted HR, 0.66).
Data source: A randomized, open-label phase II clinical trial of first-line treatment for 157 adults.
Disclosures: The study was supported by the National Institutes of Health and Exelixis, which provided the cabozantinib. Dr. Choueiri and many of his associates reported ties to numerous industry sources.
Calcipotriene-Betamethasone Dipropionate Foam in the Management of Psioriasis: A Panoramic View of Available Studies with Emphasis on Clinical Relevance
In this supplement you will learn about:
- The formulation characteristics of calcipotriene-betamethasone dipropionate aerosol foam (Cal/BD-AF)
- The efficacy and safety of Cal/BD-AF
- The results of Phase III clinical trials completed with Cal/BD-AF
James Q. Del Rosso, DO, FAOCD, FAAD
Adjunct Clinical Professor (Dermatology), Touro University Nevada, Henderson, Nevada
Lakes Dermatology and Del Rosso Dermatology Research Center, Las Vegas, Nevada
Dr. Del Rosso discloses that he is a consultant, speaker, and researcher for LEO Pharma Inc. Related to this subject area he is also a consultant, speaker, and/or researcher for Aqua Pharmaceuticals/Almirall, S.A.; Bayer AG; Celgene Corporation; Galderma Laboratories, L.P.; Genentech, Inc.; Novan, Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc. /Anacor Pharmaceuticals, Inc.; PharmaDerm; Promius Pharma, LLC; Sun Pharmaceutical Industries, Ltd.; and Valeant Pharmaceuticals International, Inc.
In this supplement you will learn about:
- The formulation characteristics of calcipotriene-betamethasone dipropionate aerosol foam (Cal/BD-AF)
- The efficacy and safety of Cal/BD-AF
- The results of Phase III clinical trials completed with Cal/BD-AF
James Q. Del Rosso, DO, FAOCD, FAAD
Adjunct Clinical Professor (Dermatology), Touro University Nevada, Henderson, Nevada
Lakes Dermatology and Del Rosso Dermatology Research Center, Las Vegas, Nevada
Dr. Del Rosso discloses that he is a consultant, speaker, and researcher for LEO Pharma Inc. Related to this subject area he is also a consultant, speaker, and/or researcher for Aqua Pharmaceuticals/Almirall, S.A.; Bayer AG; Celgene Corporation; Galderma Laboratories, L.P.; Genentech, Inc.; Novan, Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc. /Anacor Pharmaceuticals, Inc.; PharmaDerm; Promius Pharma, LLC; Sun Pharmaceutical Industries, Ltd.; and Valeant Pharmaceuticals International, Inc.
In this supplement you will learn about:
- The formulation characteristics of calcipotriene-betamethasone dipropionate aerosol foam (Cal/BD-AF)
- The efficacy and safety of Cal/BD-AF
- The results of Phase III clinical trials completed with Cal/BD-AF
James Q. Del Rosso, DO, FAOCD, FAAD
Adjunct Clinical Professor (Dermatology), Touro University Nevada, Henderson, Nevada
Lakes Dermatology and Del Rosso Dermatology Research Center, Las Vegas, Nevada
Dr. Del Rosso discloses that he is a consultant, speaker, and researcher for LEO Pharma Inc. Related to this subject area he is also a consultant, speaker, and/or researcher for Aqua Pharmaceuticals/Almirall, S.A.; Bayer AG; Celgene Corporation; Galderma Laboratories, L.P.; Genentech, Inc.; Novan, Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc. /Anacor Pharmaceuticals, Inc.; PharmaDerm; Promius Pharma, LLC; Sun Pharmaceutical Industries, Ltd.; and Valeant Pharmaceuticals International, Inc.
USPSTF: Expand statin use beyond lipids to CVD risk
Use of statins for the primary prevention of cardiovascular disease should be based on overall cardiovascular disease risk, not necessarily blood lipid levels, according to new recommendations from the United States Preventive Services Task Force.
Despite widespread use in the elderly, USPSTF also said there’s insufficient evidence to recommend starting statins for cardiovascular disease (CVD) prevention in patients 76 years or older (JAMA. 2016 Nov;316[19]:1997-2007).
USPSTF now recommends low- to moderate-dose statins for primary prevention in adults 40-75 years old who have at least one CVD risk factor – dyslipidemia, diabetes, hypertension, or smoking – and a 10-year CVD event risk of at least 10% (B grade). It also recommended “selectively” offering low- to moderate-dose statins if patients have a 7.5%-10% risk (C grade). The task force recommends using the online American College of Cardiology/American Heart Association risk calculator.
A B grade denotes that USPSTF recommends the service as one where there is “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.” With a C grade, the task force recommends that the service be provided subject to professional judgment and patient preferences.
The new advices from USPSTF is consistent with the task force’s 2015 draft proposals, and is based on a pooled analysis of 19 randomized trials in 71,344 adults at risk for CVD but without prior events; 17 of the studies were sponsored at least in part by the companies that make statins. The median duration of follow-up was 3 years. Trials included atorvastatin (Lipitor) and six other statins from 1994-2016.
Few of the 19 trials enrolled patients older than 75 years, so “the balance of benefits and harms of initiating statin use for” primary prevention in elderly adults “cannot be determined.” The task force did not make a recommendation either way, and called for further investigation.
For younger patients, the scales tipped toward benefit when the group found no overall increased risk of cancer, liver damage, diabetes, or cognitive problems with statins for primary prevention. “Although muscle pain, soreness, or weakness are commonly reported with statin use, there were no statistically significant differences between the intervention and control groups for myalgia, myopathy, or rhabdomyolysis,” according to the task force.
Across the 19 trials, statin therapy was associated with a statistically significant 14% reduction in all-cause mortality; 31% reduction in cardiovascular mortality; 29% reduction in stroke; and a 36% reduction in myocardial infarction; 250 patients needed to be treated to prevent one death from any cause after 1-6 years, and 233 to prevent one cardiovascular death after 2-6 years.
The recommendations call for low to moderate doses because that’s what most of the studies used, and there were no clear benefits when trials stratified patients by dose.
USPSTF cautioned that “reliance on a risk calculator ... alone as a basis for prevention may be problematic, given its possible overestimation of risk in some populations” and noted that the benefits “of statin use may be linear according to a patient’s absolute risk level, and any cut points used are only population estimates of benefits.”
The recommendations do not pertain to adults with very high CVD risk, such as those with familial hypercholesterolemia or an LDL level greater than 190mg/dL, since they were excluded from primary prevention trials.
While the USPSTF was careful in its evidence review, “ the limitations of the evidence were not considered sufficiently, given the serious concerns about the harms of statins for primary prevention,” Rita Redberg, MD, and Mitchell Katz, MD, wrote in an editorial accompanying the recommendations.
“USPSTF also did not have access to patient-level data; they had to rely on peer-reviewed published reports,” according to the editorialists. “The actual trial data are largely held by the Cholesterol Treatment Trialists’ Collaboration on behalf of industry sponsors and have not been made available to other researchers, despite multiple requests over many years.” Further, many of the trials were industry sponsored.
Using the USPSTF data, only 2% of patients who take statins for 5 years will avoid a myocardial infarction; virtually all (98%) will not experience any benefit. At the same time, 5%-20% will experience side effects including rhabdomyolysis, cognitive dysfunction, and increased risk of diabetes (JAMA. 2016 Nov;316[19]:1979-81).
There are unintended consequences of widespread statin use in healthy persons, Dr. Redberg and Dr. Katz wrote. People taking statins are more likely to become obese and more sedentary over time, likely because they mistakenly think they do not need to eat a healthy diet and exercise.
The USPSTF analysis was funded by the Agency for Healthcare Research and Quality. Task force lead Kirsten Bibbins-Domingo, MD, PhD, of the University of California, San Francisco, has advised the Institute for Clinical and Economic Review, which is partly funded by industry, on the cost-effectiveness of lipid-lowering drugs. Another member reported comparing how well they worked. The other 15 task force members had no disclosures.
Dare cardiovascular experts consider a future in which there are near-universal statin recommendations for middle-aged adults?
[USPSTF analysis suggests] that statin recommendations could be based primarily on a patient’s underlying CVD risk rather than on his or her cholesterol level. Disseminating a treatment strategy based largely on CVD risk alone has been a difficult message for the clinical community to accept and implement.
Nearly a generation of physicians has considered high-cholesterol levels, rather than generalized CVD risk, the target for statin treatment. Only a minority of physicians consistently use complex, risk-based probabilistic calculations to determine therapy.
Several key questions deserve careful consideration. Should LDL be considered in treatment recommendations beyond CVD risk? The decision to use absolute risk to guide statin recommendations is based on the finding that the relative risk reduction seen with statin therapy is independent of baseline risk; thus, those with the highest absolute baseline CVD risk experience the greatest reduction in CVD events.
However, the relative risk reduction of lipid-lowering therapy is also proportional to mmol/dL reduction in LDL level. This supports the contention that those with the highest baseline LDL levels should benefit the most from treatment because they have the most potential decline in LDL with intervention. One way to reconcile these findings is to incorporate both LDL levels and CVD risk into treatment recommendations, as has been done in the European guidelines. This approach recognizes that the relative benefit of statins is proportional to LDL lowering but that the absolute treatment benefit is largely driven by baseline risk.
From the resource perspective, the vast majority of statins are now available as generic products and require limited monitoring, leading to quite modest therapeutic costs. For patients in the gray area not covered by the guidelines, clinicians should be cautioned against adopting either a “treat none” or a “treat all” strategy. Rather, gaps in the evidence provide opportunities for clinicians to practice the art of medicine and engage with patients in shared decision-making regarding strategies for CVD prevention.
Ann Marie Navar, MD, PhD, and Eric Peterson, MD, MPH, are both at the Duke Clinical Research Institute in Durham, N.C. Dr. Navar reported funding from Regeneron and Sanofi. Dr. Peterson reported funding from Merck, Sanofi, Regeneron, and AstraZeneca. They made their comments in an editorial to the USPSTF report (JAMA. 2016 Nov;316[19]:1981-3).
Dare cardiovascular experts consider a future in which there are near-universal statin recommendations for middle-aged adults?
[USPSTF analysis suggests] that statin recommendations could be based primarily on a patient’s underlying CVD risk rather than on his or her cholesterol level. Disseminating a treatment strategy based largely on CVD risk alone has been a difficult message for the clinical community to accept and implement.
Nearly a generation of physicians has considered high-cholesterol levels, rather than generalized CVD risk, the target for statin treatment. Only a minority of physicians consistently use complex, risk-based probabilistic calculations to determine therapy.
Several key questions deserve careful consideration. Should LDL be considered in treatment recommendations beyond CVD risk? The decision to use absolute risk to guide statin recommendations is based on the finding that the relative risk reduction seen with statin therapy is independent of baseline risk; thus, those with the highest absolute baseline CVD risk experience the greatest reduction in CVD events.
However, the relative risk reduction of lipid-lowering therapy is also proportional to mmol/dL reduction in LDL level. This supports the contention that those with the highest baseline LDL levels should benefit the most from treatment because they have the most potential decline in LDL with intervention. One way to reconcile these findings is to incorporate both LDL levels and CVD risk into treatment recommendations, as has been done in the European guidelines. This approach recognizes that the relative benefit of statins is proportional to LDL lowering but that the absolute treatment benefit is largely driven by baseline risk.
From the resource perspective, the vast majority of statins are now available as generic products and require limited monitoring, leading to quite modest therapeutic costs. For patients in the gray area not covered by the guidelines, clinicians should be cautioned against adopting either a “treat none” or a “treat all” strategy. Rather, gaps in the evidence provide opportunities for clinicians to practice the art of medicine and engage with patients in shared decision-making regarding strategies for CVD prevention.
Ann Marie Navar, MD, PhD, and Eric Peterson, MD, MPH, are both at the Duke Clinical Research Institute in Durham, N.C. Dr. Navar reported funding from Regeneron and Sanofi. Dr. Peterson reported funding from Merck, Sanofi, Regeneron, and AstraZeneca. They made their comments in an editorial to the USPSTF report (JAMA. 2016 Nov;316[19]:1981-3).
Dare cardiovascular experts consider a future in which there are near-universal statin recommendations for middle-aged adults?
[USPSTF analysis suggests] that statin recommendations could be based primarily on a patient’s underlying CVD risk rather than on his or her cholesterol level. Disseminating a treatment strategy based largely on CVD risk alone has been a difficult message for the clinical community to accept and implement.
Nearly a generation of physicians has considered high-cholesterol levels, rather than generalized CVD risk, the target for statin treatment. Only a minority of physicians consistently use complex, risk-based probabilistic calculations to determine therapy.
Several key questions deserve careful consideration. Should LDL be considered in treatment recommendations beyond CVD risk? The decision to use absolute risk to guide statin recommendations is based on the finding that the relative risk reduction seen with statin therapy is independent of baseline risk; thus, those with the highest absolute baseline CVD risk experience the greatest reduction in CVD events.
However, the relative risk reduction of lipid-lowering therapy is also proportional to mmol/dL reduction in LDL level. This supports the contention that those with the highest baseline LDL levels should benefit the most from treatment because they have the most potential decline in LDL with intervention. One way to reconcile these findings is to incorporate both LDL levels and CVD risk into treatment recommendations, as has been done in the European guidelines. This approach recognizes that the relative benefit of statins is proportional to LDL lowering but that the absolute treatment benefit is largely driven by baseline risk.
From the resource perspective, the vast majority of statins are now available as generic products and require limited monitoring, leading to quite modest therapeutic costs. For patients in the gray area not covered by the guidelines, clinicians should be cautioned against adopting either a “treat none” or a “treat all” strategy. Rather, gaps in the evidence provide opportunities for clinicians to practice the art of medicine and engage with patients in shared decision-making regarding strategies for CVD prevention.
Ann Marie Navar, MD, PhD, and Eric Peterson, MD, MPH, are both at the Duke Clinical Research Institute in Durham, N.C. Dr. Navar reported funding from Regeneron and Sanofi. Dr. Peterson reported funding from Merck, Sanofi, Regeneron, and AstraZeneca. They made their comments in an editorial to the USPSTF report (JAMA. 2016 Nov;316[19]:1981-3).
Use of statins for the primary prevention of cardiovascular disease should be based on overall cardiovascular disease risk, not necessarily blood lipid levels, according to new recommendations from the United States Preventive Services Task Force.
Despite widespread use in the elderly, USPSTF also said there’s insufficient evidence to recommend starting statins for cardiovascular disease (CVD) prevention in patients 76 years or older (JAMA. 2016 Nov;316[19]:1997-2007).
USPSTF now recommends low- to moderate-dose statins for primary prevention in adults 40-75 years old who have at least one CVD risk factor – dyslipidemia, diabetes, hypertension, or smoking – and a 10-year CVD event risk of at least 10% (B grade). It also recommended “selectively” offering low- to moderate-dose statins if patients have a 7.5%-10% risk (C grade). The task force recommends using the online American College of Cardiology/American Heart Association risk calculator.
A B grade denotes that USPSTF recommends the service as one where there is “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.” With a C grade, the task force recommends that the service be provided subject to professional judgment and patient preferences.
The new advices from USPSTF is consistent with the task force’s 2015 draft proposals, and is based on a pooled analysis of 19 randomized trials in 71,344 adults at risk for CVD but without prior events; 17 of the studies were sponsored at least in part by the companies that make statins. The median duration of follow-up was 3 years. Trials included atorvastatin (Lipitor) and six other statins from 1994-2016.
Few of the 19 trials enrolled patients older than 75 years, so “the balance of benefits and harms of initiating statin use for” primary prevention in elderly adults “cannot be determined.” The task force did not make a recommendation either way, and called for further investigation.
For younger patients, the scales tipped toward benefit when the group found no overall increased risk of cancer, liver damage, diabetes, or cognitive problems with statins for primary prevention. “Although muscle pain, soreness, or weakness are commonly reported with statin use, there were no statistically significant differences between the intervention and control groups for myalgia, myopathy, or rhabdomyolysis,” according to the task force.
Across the 19 trials, statin therapy was associated with a statistically significant 14% reduction in all-cause mortality; 31% reduction in cardiovascular mortality; 29% reduction in stroke; and a 36% reduction in myocardial infarction; 250 patients needed to be treated to prevent one death from any cause after 1-6 years, and 233 to prevent one cardiovascular death after 2-6 years.
The recommendations call for low to moderate doses because that’s what most of the studies used, and there were no clear benefits when trials stratified patients by dose.
USPSTF cautioned that “reliance on a risk calculator ... alone as a basis for prevention may be problematic, given its possible overestimation of risk in some populations” and noted that the benefits “of statin use may be linear according to a patient’s absolute risk level, and any cut points used are only population estimates of benefits.”
The recommendations do not pertain to adults with very high CVD risk, such as those with familial hypercholesterolemia or an LDL level greater than 190mg/dL, since they were excluded from primary prevention trials.
While the USPSTF was careful in its evidence review, “ the limitations of the evidence were not considered sufficiently, given the serious concerns about the harms of statins for primary prevention,” Rita Redberg, MD, and Mitchell Katz, MD, wrote in an editorial accompanying the recommendations.
“USPSTF also did not have access to patient-level data; they had to rely on peer-reviewed published reports,” according to the editorialists. “The actual trial data are largely held by the Cholesterol Treatment Trialists’ Collaboration on behalf of industry sponsors and have not been made available to other researchers, despite multiple requests over many years.” Further, many of the trials were industry sponsored.
Using the USPSTF data, only 2% of patients who take statins for 5 years will avoid a myocardial infarction; virtually all (98%) will not experience any benefit. At the same time, 5%-20% will experience side effects including rhabdomyolysis, cognitive dysfunction, and increased risk of diabetes (JAMA. 2016 Nov;316[19]:1979-81).
There are unintended consequences of widespread statin use in healthy persons, Dr. Redberg and Dr. Katz wrote. People taking statins are more likely to become obese and more sedentary over time, likely because they mistakenly think they do not need to eat a healthy diet and exercise.
The USPSTF analysis was funded by the Agency for Healthcare Research and Quality. Task force lead Kirsten Bibbins-Domingo, MD, PhD, of the University of California, San Francisco, has advised the Institute for Clinical and Economic Review, which is partly funded by industry, on the cost-effectiveness of lipid-lowering drugs. Another member reported comparing how well they worked. The other 15 task force members had no disclosures.
Use of statins for the primary prevention of cardiovascular disease should be based on overall cardiovascular disease risk, not necessarily blood lipid levels, according to new recommendations from the United States Preventive Services Task Force.
Despite widespread use in the elderly, USPSTF also said there’s insufficient evidence to recommend starting statins for cardiovascular disease (CVD) prevention in patients 76 years or older (JAMA. 2016 Nov;316[19]:1997-2007).
USPSTF now recommends low- to moderate-dose statins for primary prevention in adults 40-75 years old who have at least one CVD risk factor – dyslipidemia, diabetes, hypertension, or smoking – and a 10-year CVD event risk of at least 10% (B grade). It also recommended “selectively” offering low- to moderate-dose statins if patients have a 7.5%-10% risk (C grade). The task force recommends using the online American College of Cardiology/American Heart Association risk calculator.
A B grade denotes that USPSTF recommends the service as one where there is “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.” With a C grade, the task force recommends that the service be provided subject to professional judgment and patient preferences.
The new advices from USPSTF is consistent with the task force’s 2015 draft proposals, and is based on a pooled analysis of 19 randomized trials in 71,344 adults at risk for CVD but without prior events; 17 of the studies were sponsored at least in part by the companies that make statins. The median duration of follow-up was 3 years. Trials included atorvastatin (Lipitor) and six other statins from 1994-2016.
Few of the 19 trials enrolled patients older than 75 years, so “the balance of benefits and harms of initiating statin use for” primary prevention in elderly adults “cannot be determined.” The task force did not make a recommendation either way, and called for further investigation.
For younger patients, the scales tipped toward benefit when the group found no overall increased risk of cancer, liver damage, diabetes, or cognitive problems with statins for primary prevention. “Although muscle pain, soreness, or weakness are commonly reported with statin use, there were no statistically significant differences between the intervention and control groups for myalgia, myopathy, or rhabdomyolysis,” according to the task force.
Across the 19 trials, statin therapy was associated with a statistically significant 14% reduction in all-cause mortality; 31% reduction in cardiovascular mortality; 29% reduction in stroke; and a 36% reduction in myocardial infarction; 250 patients needed to be treated to prevent one death from any cause after 1-6 years, and 233 to prevent one cardiovascular death after 2-6 years.
The recommendations call for low to moderate doses because that’s what most of the studies used, and there were no clear benefits when trials stratified patients by dose.
USPSTF cautioned that “reliance on a risk calculator ... alone as a basis for prevention may be problematic, given its possible overestimation of risk in some populations” and noted that the benefits “of statin use may be linear according to a patient’s absolute risk level, and any cut points used are only population estimates of benefits.”
The recommendations do not pertain to adults with very high CVD risk, such as those with familial hypercholesterolemia or an LDL level greater than 190mg/dL, since they were excluded from primary prevention trials.
While the USPSTF was careful in its evidence review, “ the limitations of the evidence were not considered sufficiently, given the serious concerns about the harms of statins for primary prevention,” Rita Redberg, MD, and Mitchell Katz, MD, wrote in an editorial accompanying the recommendations.
“USPSTF also did not have access to patient-level data; they had to rely on peer-reviewed published reports,” according to the editorialists. “The actual trial data are largely held by the Cholesterol Treatment Trialists’ Collaboration on behalf of industry sponsors and have not been made available to other researchers, despite multiple requests over many years.” Further, many of the trials were industry sponsored.
Using the USPSTF data, only 2% of patients who take statins for 5 years will avoid a myocardial infarction; virtually all (98%) will not experience any benefit. At the same time, 5%-20% will experience side effects including rhabdomyolysis, cognitive dysfunction, and increased risk of diabetes (JAMA. 2016 Nov;316[19]:1979-81).
There are unintended consequences of widespread statin use in healthy persons, Dr. Redberg and Dr. Katz wrote. People taking statins are more likely to become obese and more sedentary over time, likely because they mistakenly think they do not need to eat a healthy diet and exercise.
The USPSTF analysis was funded by the Agency for Healthcare Research and Quality. Task force lead Kirsten Bibbins-Domingo, MD, PhD, of the University of California, San Francisco, has advised the Institute for Clinical and Economic Review, which is partly funded by industry, on the cost-effectiveness of lipid-lowering drugs. Another member reported comparing how well they worked. The other 15 task force members had no disclosures.
It’s not easy to identify clinical depression in menopause
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
VIDEO: Choosing Your Path: Academic or Community Hospital Medicine?
Choosing hospital medicine as a specialty means choosing between practicing community HM or academic HM. Or does it? Elizabeth Cook, MD, of Hospital Medicine Associates in Lynchburg VA; Stella Fitzgibbon, MD, FACP, FHM, with Memorial Hermann Hospital in The Woodlands, TX; and Chris Moriates, MD, of Dell Medical School at UT Austin, talk about the options available in community and academic HM, and moving between them during an HM career.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Choosing hospital medicine as a specialty means choosing between practicing community HM or academic HM. Or does it? Elizabeth Cook, MD, of Hospital Medicine Associates in Lynchburg VA; Stella Fitzgibbon, MD, FACP, FHM, with Memorial Hermann Hospital in The Woodlands, TX; and Chris Moriates, MD, of Dell Medical School at UT Austin, talk about the options available in community and academic HM, and moving between them during an HM career.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Choosing hospital medicine as a specialty means choosing between practicing community HM or academic HM. Or does it? Elizabeth Cook, MD, of Hospital Medicine Associates in Lynchburg VA; Stella Fitzgibbon, MD, FACP, FHM, with Memorial Hermann Hospital in The Woodlands, TX; and Chris Moriates, MD, of Dell Medical School at UT Austin, talk about the options available in community and academic HM, and moving between them during an HM career.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Travel barriers can impede patient choice for pancreatectomy
AT THE ACS CLINICAL CONGRESS
WASHINGTON – Patients who have the resources to travel to higher-volume hospitals for pancreatectomy have better outcomes than do those who opt to have the surgery in local, small-volume hospitals.
A 10-year review of travel patterns associated with pancreatectomy in California found those who didn’t travel were often elderly, black or Hispanic, and were either self-pay or had public insurance.
“It’s probably because these patients don’t have the resources [finances and transportation] to travel far to the best hospitals for their surgery and have to rely on the closest hospitals for better or for worse – and it seems more like the latter,” he said in an interview at the annual clinical congress of the American College of Surgeons. “So what you see is there is an aspatial barrier to access [limited insurance], as well as spatial barriers to access.”
He and his mentor, David C. Chang, PhD, examined about 13,000 pancreatectomy records included in the California Office of Statewide Health Planning and Development database from 2005 to 2014. The research was conducted at Harvard University and the Massachusetts General Hospital, Boston.
The majority of these patients (11,000) bypassed at least one hospital that offered pancreatectomy to reach their ultimate choice. After bypassing a median of seven facilities, they ended up traveling about 16 miles from home to reach their chosen hospital. Patients who stuck to the closest hospital traveled only about 3 miles.
Generally, bypassers tended to end up in higher-volume hospitals with better outcomes. About half had their pancreatectomy at a hospital that performed more than 20 per year; 40% were at a facility that performed in excess of 40 pancreatectomies annually. Almost 50% of the bypassers also had their surgery at a teaching hospital. The median length of stay at these facilities was 10 days, and they had a median pancreatectomy mortality rate of 3%.
In contrast, patients who didn’t travel ended up at lower-volume hospitals; 60% had their pancreatectomy at a hospital that performed fewer than 10 per year and 22% at a hospital that performed 10-20 per year. Only 18% were treated at an academic center. These hospitals had a significantly longer pancreatectomy length of stay (12 days) and significantly higher pancreatectomy mortality rate (6%).
Older patients were less likely to travel. The age difference came into play beginning at age 50 and grew stronger as patients aged.
Insurance status was highly associated with hospital destination. Privately insured patients were the most likely to travel to better hospitals, followed by those on Medicare. Patients on Medicaid and those who identified as self-pay were significantly less likely to travel. Minorities traveled far less as well; blacks were the least likely to travel from their home base.
In this time of value-based surgical outcomes, the study has some interesting implications, Dr. Fong said. Many health care systems are undertaking a volume pledge, which aims to funnel patients who need high-risk procedures to centers that perform a large number of them annually. But there is a flip side to that coin, which could, in essence, make things even tougher on patients who find travel challenging.
“The Volume Pledge aims to stop hospitals that are low volume in certain procedures from continuing to do them, on the basis that high-volume hospitals often do better in terms of outcomes. But there are very much unintended consequences of the pledge, such as hampering access to surgery. Because inevitably, you’ll increase distance needed to travel for each patient to get care if low-volume hospitals stopped offering their services.”
In his study, Dr. Fong found that some California counties had only one hospital that offered pancreatectomy, and that was a low-volume facility. If that hospital was forced to stop offering the procedure, patients with less resources could face even more obstacles to getting the treatment they need.
“Eliminating [low-volume hospital procedures] will have dire consequences. Our study showed that the elderly, racial/ethnic minorities, uninsured and those on Medicaid generally don’t travel for care, and this pledge may compound on that and widen disparity or even worse, some may not even get care as a result.”
Dr. Fong had no financial disclosures.
[email protected]
On Twitter @Alz_Gal
AT THE ACS CLINICAL CONGRESS
WASHINGTON – Patients who have the resources to travel to higher-volume hospitals for pancreatectomy have better outcomes than do those who opt to have the surgery in local, small-volume hospitals.
A 10-year review of travel patterns associated with pancreatectomy in California found those who didn’t travel were often elderly, black or Hispanic, and were either self-pay or had public insurance.
“It’s probably because these patients don’t have the resources [finances and transportation] to travel far to the best hospitals for their surgery and have to rely on the closest hospitals for better or for worse – and it seems more like the latter,” he said in an interview at the annual clinical congress of the American College of Surgeons. “So what you see is there is an aspatial barrier to access [limited insurance], as well as spatial barriers to access.”
He and his mentor, David C. Chang, PhD, examined about 13,000 pancreatectomy records included in the California Office of Statewide Health Planning and Development database from 2005 to 2014. The research was conducted at Harvard University and the Massachusetts General Hospital, Boston.
The majority of these patients (11,000) bypassed at least one hospital that offered pancreatectomy to reach their ultimate choice. After bypassing a median of seven facilities, they ended up traveling about 16 miles from home to reach their chosen hospital. Patients who stuck to the closest hospital traveled only about 3 miles.
Generally, bypassers tended to end up in higher-volume hospitals with better outcomes. About half had their pancreatectomy at a hospital that performed more than 20 per year; 40% were at a facility that performed in excess of 40 pancreatectomies annually. Almost 50% of the bypassers also had their surgery at a teaching hospital. The median length of stay at these facilities was 10 days, and they had a median pancreatectomy mortality rate of 3%.
In contrast, patients who didn’t travel ended up at lower-volume hospitals; 60% had their pancreatectomy at a hospital that performed fewer than 10 per year and 22% at a hospital that performed 10-20 per year. Only 18% were treated at an academic center. These hospitals had a significantly longer pancreatectomy length of stay (12 days) and significantly higher pancreatectomy mortality rate (6%).
Older patients were less likely to travel. The age difference came into play beginning at age 50 and grew stronger as patients aged.
Insurance status was highly associated with hospital destination. Privately insured patients were the most likely to travel to better hospitals, followed by those on Medicare. Patients on Medicaid and those who identified as self-pay were significantly less likely to travel. Minorities traveled far less as well; blacks were the least likely to travel from their home base.
In this time of value-based surgical outcomes, the study has some interesting implications, Dr. Fong said. Many health care systems are undertaking a volume pledge, which aims to funnel patients who need high-risk procedures to centers that perform a large number of them annually. But there is a flip side to that coin, which could, in essence, make things even tougher on patients who find travel challenging.
“The Volume Pledge aims to stop hospitals that are low volume in certain procedures from continuing to do them, on the basis that high-volume hospitals often do better in terms of outcomes. But there are very much unintended consequences of the pledge, such as hampering access to surgery. Because inevitably, you’ll increase distance needed to travel for each patient to get care if low-volume hospitals stopped offering their services.”
In his study, Dr. Fong found that some California counties had only one hospital that offered pancreatectomy, and that was a low-volume facility. If that hospital was forced to stop offering the procedure, patients with less resources could face even more obstacles to getting the treatment they need.
“Eliminating [low-volume hospital procedures] will have dire consequences. Our study showed that the elderly, racial/ethnic minorities, uninsured and those on Medicaid generally don’t travel for care, and this pledge may compound on that and widen disparity or even worse, some may not even get care as a result.”
Dr. Fong had no financial disclosures.
[email protected]
On Twitter @Alz_Gal
AT THE ACS CLINICAL CONGRESS
WASHINGTON – Patients who have the resources to travel to higher-volume hospitals for pancreatectomy have better outcomes than do those who opt to have the surgery in local, small-volume hospitals.
A 10-year review of travel patterns associated with pancreatectomy in California found those who didn’t travel were often elderly, black or Hispanic, and were either self-pay or had public insurance.
“It’s probably because these patients don’t have the resources [finances and transportation] to travel far to the best hospitals for their surgery and have to rely on the closest hospitals for better or for worse – and it seems more like the latter,” he said in an interview at the annual clinical congress of the American College of Surgeons. “So what you see is there is an aspatial barrier to access [limited insurance], as well as spatial barriers to access.”
He and his mentor, David C. Chang, PhD, examined about 13,000 pancreatectomy records included in the California Office of Statewide Health Planning and Development database from 2005 to 2014. The research was conducted at Harvard University and the Massachusetts General Hospital, Boston.
The majority of these patients (11,000) bypassed at least one hospital that offered pancreatectomy to reach their ultimate choice. After bypassing a median of seven facilities, they ended up traveling about 16 miles from home to reach their chosen hospital. Patients who stuck to the closest hospital traveled only about 3 miles.
Generally, bypassers tended to end up in higher-volume hospitals with better outcomes. About half had their pancreatectomy at a hospital that performed more than 20 per year; 40% were at a facility that performed in excess of 40 pancreatectomies annually. Almost 50% of the bypassers also had their surgery at a teaching hospital. The median length of stay at these facilities was 10 days, and they had a median pancreatectomy mortality rate of 3%.
In contrast, patients who didn’t travel ended up at lower-volume hospitals; 60% had their pancreatectomy at a hospital that performed fewer than 10 per year and 22% at a hospital that performed 10-20 per year. Only 18% were treated at an academic center. These hospitals had a significantly longer pancreatectomy length of stay (12 days) and significantly higher pancreatectomy mortality rate (6%).
Older patients were less likely to travel. The age difference came into play beginning at age 50 and grew stronger as patients aged.
Insurance status was highly associated with hospital destination. Privately insured patients were the most likely to travel to better hospitals, followed by those on Medicare. Patients on Medicaid and those who identified as self-pay were significantly less likely to travel. Minorities traveled far less as well; blacks were the least likely to travel from their home base.
In this time of value-based surgical outcomes, the study has some interesting implications, Dr. Fong said. Many health care systems are undertaking a volume pledge, which aims to funnel patients who need high-risk procedures to centers that perform a large number of them annually. But there is a flip side to that coin, which could, in essence, make things even tougher on patients who find travel challenging.
“The Volume Pledge aims to stop hospitals that are low volume in certain procedures from continuing to do them, on the basis that high-volume hospitals often do better in terms of outcomes. But there are very much unintended consequences of the pledge, such as hampering access to surgery. Because inevitably, you’ll increase distance needed to travel for each patient to get care if low-volume hospitals stopped offering their services.”
In his study, Dr. Fong found that some California counties had only one hospital that offered pancreatectomy, and that was a low-volume facility. If that hospital was forced to stop offering the procedure, patients with less resources could face even more obstacles to getting the treatment they need.
“Eliminating [low-volume hospital procedures] will have dire consequences. Our study showed that the elderly, racial/ethnic minorities, uninsured and those on Medicaid generally don’t travel for care, and this pledge may compound on that and widen disparity or even worse, some may not even get care as a result.”
Dr. Fong had no financial disclosures.
[email protected]
On Twitter @Alz_Gal
Key clinical point:
Major finding: About 60% of patients who didn’t travel had surgery at a low-volume hospital with a higher mortality rate and longer length of stay.
Data source: The 10-year California database review comprised 13,000 patients.
Disclosures: Dr. Fong had no financial disclosures.
Challenges of influenza, measles, pertussis guide outbreak management
SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.
Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.
Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
Influenza
The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.
The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
Pertussis
Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.
It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.
One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.
Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
Measles
The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.
Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.
Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.
“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.
When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.
The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.
“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”
For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.
“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
Managing suspected/confirmed outbreaks
To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:
• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.
• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.
• Prevent additional cases using screening questions at the front desk.
• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.
• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.
• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.
Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.
SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.
Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.
Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
Influenza
The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.
The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
Pertussis
Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.
It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.
One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.
Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
Measles
The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.
Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.
Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.
“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.
When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.
The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.
“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”
For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.
“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
Managing suspected/confirmed outbreaks
To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:
• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.
• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.
• Prevent additional cases using screening questions at the front desk.
• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.
• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.
• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.
Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.
SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.
Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.
Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
Influenza
The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.
The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
Pertussis
Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.
It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.
One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.
Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
Measles
The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.
Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.
Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.
“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.
When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.
The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.
“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”
For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.
“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
Managing suspected/confirmed outbreaks
To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:
• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.
• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.
• Prevent additional cases using screening questions at the front desk.
• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.
• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.
• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.
Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.
FROM AAP 16
Weight Watchers program shows efficacy in controlling type 2 diabetes
NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.
This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.
“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”
Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.
Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.
At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A1clevel was 7%-11% and their body mass index was 27-50 kg/m2.
Both weight loss and improvement in HbA1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.
When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA1c, and 24% of patients in that study arm had achieved an HbA1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA1c, and only 14% of controls got their HbA1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.
While the 0.48% difference in HbA1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.
Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.
Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.
Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).
The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.
NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.
This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.
“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”
Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.
Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.
At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A1clevel was 7%-11% and their body mass index was 27-50 kg/m2.
Both weight loss and improvement in HbA1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.
When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA1c, and 24% of patients in that study arm had achieved an HbA1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA1c, and only 14% of controls got their HbA1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.
While the 0.48% difference in HbA1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.
Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.
Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.
Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).
The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.
NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.
This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.
“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”
Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.
Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.
At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A1clevel was 7%-11% and their body mass index was 27-50 kg/m2.
Both weight loss and improvement in HbA1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.
When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA1c, and 24% of patients in that study arm had achieved an HbA1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA1c, and only 14% of controls got their HbA1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.
While the 0.48% difference in HbA1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.
Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.
Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.
Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).
The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.
Key clinical point:
Major finding: Overweight or obese patients with inadequately controlled type 2 diabetes experienced a mean 0.32% decrease in HbA1c and 4% reduction in body weight over the course of 52 weeks on the commercially available Weight Watchers program supplemented by telephone and email counseling by a certified diabetes educator, significantly better outcomes than seen in a standard care control group.
Data source: A 52-week, multicenter, randomized controlled trial in 563 obese or overweight adults with inadequately controlled type 2 diabetes.
Disclosures: The study was funded by Weight Watchers International. The presenter reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.
VIDEO: Blood pressure and LDL lowering in elderly do not slow cognitive decline
NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Nearly 6 years of blood pressure lowering and statin therapy in elderly patients with moderate vascular risk did not prevent cognitive decline relative to placebo, but the treatment did not worsen it, either.
Data source: This analysis of cognitive and functional outcomes in the randomized multicenter HOPE-3 trial included 1,626 participants who were at least 70 years old at baseline, when they were randomized to blood pressure lowering or placebo and rosuvastatin or placebo and followed for a mean of 5.6 years.
Disclosures: The HOPE-3 study was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. The presenter reported having no financial conflicts of interest.
VIDEO: Obeticholic acid resulted in reduction of a biomarker for liver fibrosis in PBC
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
AT THE LIVER MEETING 2016
