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Insurance approvals are hard to get for new PCSK9 inhibitors
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
Insurance approval rates for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are strikingly low, according to a study published in Circulation.
Two approved PCSK9i drugs, alirocumab and evolocumab, were approved for coverage just 47% of the time. Because of their high price tag – about $14,000 per year – researchers had expected low rates of insurance coverage for the novel drugs, which encourage degradation of low-density lipoprotein cholesterol by blocking preserving LDL-C receptors in hepatocytes. However, they were surprised at the size of the problem.
“I think we knew that physicians were having challenges, but the number [of coverage approvals] was maybe lower than we expected,” Robert Yeh, MD, the study’s lead investigator, said in an interview. “Physicians and patients need to be aware that in perhaps the majority of cases, when they decide these drugs are going to be ones they want to prescribe, there may be a long procedure ahead of them, and they may ultimately not succeed in getting those medications.”
PCSK9 inhibitors are specifically approved for patients with familial hypercholesterolemia, or those with atherosclerotic cardiovascular disease who are unable to achieve satisfactory lipid levels through dietary measures and statin use.
Yet insurance coverage rates were low, even when patients met labeled indications. When the researchers examined the factors associated with insurance coverage, the most important factor was the type of insurance: Commercial third-party insurers approved the drugs about 24% of the time, while Medicare approved them nearly 61% of the time (P less than .01).
Older age, prescriptions by a cardiologist or other specialist, and a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) were also associated with higher rates of coverage by insurers (Circulation. 2017 Oct 30. doi: 10.1161/CIRCULATIONAHA.117.028430).
The researchers analyzed data from 9,357 patients with a prescription for a PCSK9 inhibitor. About 60% of the patients had a diagnosis of clinical ASCVD. In all, 4,397 patients (47%) had their prescriptions for PCSK9 inhibitor therapy covered, and 53% of coverage requests were rejected. Nearly 65% of patients who received approval went on to fill their prescription.
There was no association between LDL-C level and the likelihood of approval. In the 32 cases in which the LDL-C levels were 330 mg/dL or greater, 59% of patients were not approved for coverage.
Noncommercial payers were more likely to approve the medication (odds ratio, 12.32; 95% confidence interval, 7.09-21.39), as was Medicare (OR, 5.37; 95% CI, 4.23-6.80).
A recent cost-effectiveness analysis of evolocumab added to standard therapy showed that an annual cost of $9,669 would achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life year gained among patients with LDL levels 70 mg/dL or greater. (JAMA Cardiol. 2017;2[10]:1069-78). Evolocumab is currently listed at $14,523, putting it above that value.
“Now that clinical trial outcome data demonstrating reductions in major cardiovascular events and formal cost-effectiveness studies have identified value-based prices for these medications, it would be hoped that progress can be made such that a greater proportion of eligible patients can be treated,” Gregg C. Fonarow, MD, professor of cardiovascular medicine and science director at the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and the lead author of the cost-effectiveness study, said in an interview.
Both sets of findings cut to the heart of the debate over pricing of new medications. PCSK9 inhibitors have a clear benefit in lowering LDL and reducing risk of heart attack, but the drugs’ price tags may limit their availability.
“We need to not be afraid to discuss these issues in plain terms that are not emotional, so that we can get a better sense of what is the amount to spend on a therapy, even when it is effective but potentially pricey,” said Dr. Yeh, director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center, Boston. “This is a really important business, philosophical, medical, and ethical debate.”
The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
FROM CIRCULATION
Key clinical point:
Major finding: Just 47% of PCSK9 inhibitor prescriptions were approved by insurers.
Data source: Retrospective analysis of data from 9,357 patients who were prescribed a PCSK9 inhibitor.
Disclosures: The study received no external funding. Dr. Yeh reported having no financial disclosures. Dr. Fonarow has consulted for Amgen.
New narcolepsy drug passes phase 3 test
SAN DIEGO – The selective dopamine and norepinephrine reuptake inhibitor solriamfetol is effective in reducing sleepiness in patients with narcolepsy, according to results of a phase 3 study.
At 150-mg and 300-mg doses, the drug had statistically significant effects on objective and subjective measures.
There are wake-promoting drugs available, such as amphetamine-related drugs that are often used off label, but addiction liability is a concern. The nonamphetamine modafinil has been approved by the Food and Drug Administration since 1998.
Jazz Pharmaceuticals is in the process of submitting solriamfetol for FDA evaluation. If approved, the drug will add to the options available for narcolepsy patients. “All of the available drugs have some limitations. Some have more abuse liability than others. Some have more robust wake-promoting properties than others. We haven’t done any head-to-head comparisons, so I can’t tell you how we will stack up,” Philip Jochelson, MD, said in an interview. Dr. Jochelson is vice president of clinical development at Jazz Pharmaceuticals and presented the results of the study at a poster session at the annual meeting of the American Neurological Association.
An earlier study showed the drug had less abuse potential than the schedule IV stimulant phentermine. That’s not surprising given the drug’s mechanism of action, Dr. Jochelson said. Amphetamine-based drugs stimulate dopamine release, which can prompt a dopamine surge that people equate with a high, he said. Solriamfetol also affects dopamine, but it is a reuptake inhibitor, so it doesn’t produce a surge.
If the drug gains approval, it remains to be seen how it will be classified on the Drug Enforcement Agency Controlled Substance scale. “Where it will fall in that spectrum is speculative at this point,” said Dr. Jochelson.
In the current study, 236 adults (aged 18-75 years) with type 1 narcolepsy were randomized to once-daily placebo, 75 mg solriamfetol, 150 mg solriamfetol, or 300 mg solriamfetol; 27.1% of patients in the 300-mg group discontinued, compared with 7.3% in the 150-mg group, 16.9% in the 75-mg group, and 10.3% in the placebo group. The mean change from baseline on the Maintenance of Wakefulness Test was statistically significant in the 300-mg group (12.3 minutes vs. 2.1 minutes for placebo, P less than .0001) and the 150-mg group (9.8 minutes vs. 2.1 minutes, P less than .0001) but not the 75-mg group (4.7 minutes vs. 2.1 minutes).
The drug also outperformed placebo at week 12 on the Epworth Sleepiness Scale. The mean change in the 300-mg group was –6.4 vs. –1.6 for placebo (P less than .001), –5.4 in the 150-mg group (P less than .0001), and –3.8 in the 75-mg group (P less than .05).
By both Maintenance of Wakefulness Test and Epworth Sleepiness Scale measures, the 150-mg and 300-mg solriamfetol groups had statistically significant differences as early as week 1.
The drug had some adverse effects, which were expected based on its pharmacologic profile. These included increases in headache (5.1% with placebo, 10.2% with 75 mg, 23.7% with 150 mg, 30.5% with 300 mg), nausea (1.7% for placebo, 5.1% for 75 mg, 10.2% for 150 mg, 16.9% for 300 mg), anxiety (1.7% with placebo, 1.7% with 75 mg, 5.1% with 150 mg, 8.5% with 300 mg), and insomnia (0% for placebo, 3.4% for 75 mg, 0% for 150 mg, 5.1% for 300 mg). Other adverse events occurring in at least 5% of patients were decreased appetite, nasopharyngitis, and dry mouth.
The study was funded by Jazz Pharmaceuticals. Dr. Jochelson is an employee of Jazz.
SAN DIEGO – The selective dopamine and norepinephrine reuptake inhibitor solriamfetol is effective in reducing sleepiness in patients with narcolepsy, according to results of a phase 3 study.
At 150-mg and 300-mg doses, the drug had statistically significant effects on objective and subjective measures.
There are wake-promoting drugs available, such as amphetamine-related drugs that are often used off label, but addiction liability is a concern. The nonamphetamine modafinil has been approved by the Food and Drug Administration since 1998.
Jazz Pharmaceuticals is in the process of submitting solriamfetol for FDA evaluation. If approved, the drug will add to the options available for narcolepsy patients. “All of the available drugs have some limitations. Some have more abuse liability than others. Some have more robust wake-promoting properties than others. We haven’t done any head-to-head comparisons, so I can’t tell you how we will stack up,” Philip Jochelson, MD, said in an interview. Dr. Jochelson is vice president of clinical development at Jazz Pharmaceuticals and presented the results of the study at a poster session at the annual meeting of the American Neurological Association.
An earlier study showed the drug had less abuse potential than the schedule IV stimulant phentermine. That’s not surprising given the drug’s mechanism of action, Dr. Jochelson said. Amphetamine-based drugs stimulate dopamine release, which can prompt a dopamine surge that people equate with a high, he said. Solriamfetol also affects dopamine, but it is a reuptake inhibitor, so it doesn’t produce a surge.
If the drug gains approval, it remains to be seen how it will be classified on the Drug Enforcement Agency Controlled Substance scale. “Where it will fall in that spectrum is speculative at this point,” said Dr. Jochelson.
In the current study, 236 adults (aged 18-75 years) with type 1 narcolepsy were randomized to once-daily placebo, 75 mg solriamfetol, 150 mg solriamfetol, or 300 mg solriamfetol; 27.1% of patients in the 300-mg group discontinued, compared with 7.3% in the 150-mg group, 16.9% in the 75-mg group, and 10.3% in the placebo group. The mean change from baseline on the Maintenance of Wakefulness Test was statistically significant in the 300-mg group (12.3 minutes vs. 2.1 minutes for placebo, P less than .0001) and the 150-mg group (9.8 minutes vs. 2.1 minutes, P less than .0001) but not the 75-mg group (4.7 minutes vs. 2.1 minutes).
The drug also outperformed placebo at week 12 on the Epworth Sleepiness Scale. The mean change in the 300-mg group was –6.4 vs. –1.6 for placebo (P less than .001), –5.4 in the 150-mg group (P less than .0001), and –3.8 in the 75-mg group (P less than .05).
By both Maintenance of Wakefulness Test and Epworth Sleepiness Scale measures, the 150-mg and 300-mg solriamfetol groups had statistically significant differences as early as week 1.
The drug had some adverse effects, which were expected based on its pharmacologic profile. These included increases in headache (5.1% with placebo, 10.2% with 75 mg, 23.7% with 150 mg, 30.5% with 300 mg), nausea (1.7% for placebo, 5.1% for 75 mg, 10.2% for 150 mg, 16.9% for 300 mg), anxiety (1.7% with placebo, 1.7% with 75 mg, 5.1% with 150 mg, 8.5% with 300 mg), and insomnia (0% for placebo, 3.4% for 75 mg, 0% for 150 mg, 5.1% for 300 mg). Other adverse events occurring in at least 5% of patients were decreased appetite, nasopharyngitis, and dry mouth.
The study was funded by Jazz Pharmaceuticals. Dr. Jochelson is an employee of Jazz.
SAN DIEGO – The selective dopamine and norepinephrine reuptake inhibitor solriamfetol is effective in reducing sleepiness in patients with narcolepsy, according to results of a phase 3 study.
At 150-mg and 300-mg doses, the drug had statistically significant effects on objective and subjective measures.
There are wake-promoting drugs available, such as amphetamine-related drugs that are often used off label, but addiction liability is a concern. The nonamphetamine modafinil has been approved by the Food and Drug Administration since 1998.
Jazz Pharmaceuticals is in the process of submitting solriamfetol for FDA evaluation. If approved, the drug will add to the options available for narcolepsy patients. “All of the available drugs have some limitations. Some have more abuse liability than others. Some have more robust wake-promoting properties than others. We haven’t done any head-to-head comparisons, so I can’t tell you how we will stack up,” Philip Jochelson, MD, said in an interview. Dr. Jochelson is vice president of clinical development at Jazz Pharmaceuticals and presented the results of the study at a poster session at the annual meeting of the American Neurological Association.
An earlier study showed the drug had less abuse potential than the schedule IV stimulant phentermine. That’s not surprising given the drug’s mechanism of action, Dr. Jochelson said. Amphetamine-based drugs stimulate dopamine release, which can prompt a dopamine surge that people equate with a high, he said. Solriamfetol also affects dopamine, but it is a reuptake inhibitor, so it doesn’t produce a surge.
If the drug gains approval, it remains to be seen how it will be classified on the Drug Enforcement Agency Controlled Substance scale. “Where it will fall in that spectrum is speculative at this point,” said Dr. Jochelson.
In the current study, 236 adults (aged 18-75 years) with type 1 narcolepsy were randomized to once-daily placebo, 75 mg solriamfetol, 150 mg solriamfetol, or 300 mg solriamfetol; 27.1% of patients in the 300-mg group discontinued, compared with 7.3% in the 150-mg group, 16.9% in the 75-mg group, and 10.3% in the placebo group. The mean change from baseline on the Maintenance of Wakefulness Test was statistically significant in the 300-mg group (12.3 minutes vs. 2.1 minutes for placebo, P less than .0001) and the 150-mg group (9.8 minutes vs. 2.1 minutes, P less than .0001) but not the 75-mg group (4.7 minutes vs. 2.1 minutes).
The drug also outperformed placebo at week 12 on the Epworth Sleepiness Scale. The mean change in the 300-mg group was –6.4 vs. –1.6 for placebo (P less than .001), –5.4 in the 150-mg group (P less than .0001), and –3.8 in the 75-mg group (P less than .05).
By both Maintenance of Wakefulness Test and Epworth Sleepiness Scale measures, the 150-mg and 300-mg solriamfetol groups had statistically significant differences as early as week 1.
The drug had some adverse effects, which were expected based on its pharmacologic profile. These included increases in headache (5.1% with placebo, 10.2% with 75 mg, 23.7% with 150 mg, 30.5% with 300 mg), nausea (1.7% for placebo, 5.1% for 75 mg, 10.2% for 150 mg, 16.9% for 300 mg), anxiety (1.7% with placebo, 1.7% with 75 mg, 5.1% with 150 mg, 8.5% with 300 mg), and insomnia (0% for placebo, 3.4% for 75 mg, 0% for 150 mg, 5.1% for 300 mg). Other adverse events occurring in at least 5% of patients were decreased appetite, nasopharyngitis, and dry mouth.
The study was funded by Jazz Pharmaceuticals. Dr. Jochelson is an employee of Jazz.
AT ANA 2017
Key clinical point: Solriamfetol outperformed placebo on both objective and subjective sleep measures.
Major finding: At 12 weeks, 150 mg increased Maintenance of Wakefulness Test score to 9.8 minutes, compared with 2.1 minutes in the placebo group.
Data source: A randomized, controlled trial (n = 236).
Disclosures: The study was funded by Jazz Pharmaceuticals. Dr. Jochelson is an employee of Jazz.
Stroke cognitive outcomes found worse in Mexican Americans
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
AT ANA 2017
Key clinical point: In an analysis, cognitive outcomes were worse in Mexican-American stroke survivors despite researchers’ controlling for many factors.
Major finding: At 12 months, Mexican Americans scored 6 points lower on the Modified Mini-Mental State Examination compared with non-Hispanic whites.
Data source: Prospective analysis of 227 stroke patients in Corpus Christi, Texas.
Disclosures: The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
VIDEO: Salvageable brain tissue can guide decision for stroke thrombectomy
SAN DIEGO – Neurologists have long suspected that some stroke patients could benefit from thrombectomy many hours after they were last seen well. But lingering doubts remained, and physicians weren’t sure which stroke patients were likely to improve.
Now, with the early stoppage of two key clinical trials, the answer is clear, Jeffrey Saver, MD, director of the stroke unit at the University of California, Los Angeles, said in a video interview at the annual meeting of the American Neurological Association.
At the European Stroke Organization Conference in May, Stryker Neurovascular announced the results of its DAWN trial, which tested the company’s mechanical thrombectomy device in patients who’d suffered a stroke within the past 6-24 hours and in whom imaging showed a clinical core mismatch. It was stopped early based on an interim analysis after it met multiple prespecified stopping criteria. At 90 days, 48.6% of patients in the treatment group were functionally independent, compared with 13.1% who received only medical management.
The DEFUSE 3 trial examined endovascular thrombectomy in patients 6-16 hours after a stroke who appeared to have salvageable brain tissue based on target mismatch profile with a less extreme core than in DAWN. It too was halted early because of a high probability of efficacy. Together, the trials suggest neurologists are entering a new era of treating based on tissue and not just time, Dr. Saver said.
SAN DIEGO – Neurologists have long suspected that some stroke patients could benefit from thrombectomy many hours after they were last seen well. But lingering doubts remained, and physicians weren’t sure which stroke patients were likely to improve.
Now, with the early stoppage of two key clinical trials, the answer is clear, Jeffrey Saver, MD, director of the stroke unit at the University of California, Los Angeles, said in a video interview at the annual meeting of the American Neurological Association.
At the European Stroke Organization Conference in May, Stryker Neurovascular announced the results of its DAWN trial, which tested the company’s mechanical thrombectomy device in patients who’d suffered a stroke within the past 6-24 hours and in whom imaging showed a clinical core mismatch. It was stopped early based on an interim analysis after it met multiple prespecified stopping criteria. At 90 days, 48.6% of patients in the treatment group were functionally independent, compared with 13.1% who received only medical management.
The DEFUSE 3 trial examined endovascular thrombectomy in patients 6-16 hours after a stroke who appeared to have salvageable brain tissue based on target mismatch profile with a less extreme core than in DAWN. It too was halted early because of a high probability of efficacy. Together, the trials suggest neurologists are entering a new era of treating based on tissue and not just time, Dr. Saver said.
SAN DIEGO – Neurologists have long suspected that some stroke patients could benefit from thrombectomy many hours after they were last seen well. But lingering doubts remained, and physicians weren’t sure which stroke patients were likely to improve.
Now, with the early stoppage of two key clinical trials, the answer is clear, Jeffrey Saver, MD, director of the stroke unit at the University of California, Los Angeles, said in a video interview at the annual meeting of the American Neurological Association.
At the European Stroke Organization Conference in May, Stryker Neurovascular announced the results of its DAWN trial, which tested the company’s mechanical thrombectomy device in patients who’d suffered a stroke within the past 6-24 hours and in whom imaging showed a clinical core mismatch. It was stopped early based on an interim analysis after it met multiple prespecified stopping criteria. At 90 days, 48.6% of patients in the treatment group were functionally independent, compared with 13.1% who received only medical management.
The DEFUSE 3 trial examined endovascular thrombectomy in patients 6-16 hours after a stroke who appeared to have salvageable brain tissue based on target mismatch profile with a less extreme core than in DAWN. It too was halted early because of a high probability of efficacy. Together, the trials suggest neurologists are entering a new era of treating based on tissue and not just time, Dr. Saver said.
AT ANA 2017
VIDEO: Mobile stroke units aren’t just expensive toys
SAN DIEGO – Mobile stroke units are specially equipped ambulance units designed to respond and deliver treatment to stroke patients as swiftly as possible. They are outfitted with a portable CT scanner, a mobile lab, and specialized personnel, including a telemedicine unit to assist with diagnosis. If a patient is experiencing an ischemic stroke, the unit can deliver thrombolytic therapy on the spot, circumventing travel to an emergency department.
But are they cost effective? There are 13 active units in the United States, and they’re not cheap. They cost about $3.5 million to build and operate over 5 years, according to James Grotta, MD, a neurologist with the Memorial Hermann Medical Group and director of stroke research at Memorial Hermann–Texas Medical Center, both in Houston.
In a video interview at the annual meeting of the American Neurological Association, Dr. Grotta described how his group is studying the impact of mobile stroke units on time to treatment and the long-term costs and cost savings associated with them in an ongoing clinical trial that is comparing outcomes in patients eligible for tissue plasminogen activator when treated by a mobile stroke unit versus standard prehospital triage and transport by emergency medical services. The study is comparing outcomes when the mobile stroke unit and emergency medical services are the primary responders on alternating weeks. Primary outcomes include cost-effectiveness, the change in Rankin scale score from baseline to 90 days, and the diagnostic agreement between a vascular neurologist in the mobile stroke unit and a telemedicine vascular neurologist consulted from the unit.
Mobile stroke units can even supplement existing health care in case of an emergency. Dr. Grotta also recounted how one unit assisted during the aftermath of Hurricane Harvey.
SAN DIEGO – Mobile stroke units are specially equipped ambulance units designed to respond and deliver treatment to stroke patients as swiftly as possible. They are outfitted with a portable CT scanner, a mobile lab, and specialized personnel, including a telemedicine unit to assist with diagnosis. If a patient is experiencing an ischemic stroke, the unit can deliver thrombolytic therapy on the spot, circumventing travel to an emergency department.
But are they cost effective? There are 13 active units in the United States, and they’re not cheap. They cost about $3.5 million to build and operate over 5 years, according to James Grotta, MD, a neurologist with the Memorial Hermann Medical Group and director of stroke research at Memorial Hermann–Texas Medical Center, both in Houston.
In a video interview at the annual meeting of the American Neurological Association, Dr. Grotta described how his group is studying the impact of mobile stroke units on time to treatment and the long-term costs and cost savings associated with them in an ongoing clinical trial that is comparing outcomes in patients eligible for tissue plasminogen activator when treated by a mobile stroke unit versus standard prehospital triage and transport by emergency medical services. The study is comparing outcomes when the mobile stroke unit and emergency medical services are the primary responders on alternating weeks. Primary outcomes include cost-effectiveness, the change in Rankin scale score from baseline to 90 days, and the diagnostic agreement between a vascular neurologist in the mobile stroke unit and a telemedicine vascular neurologist consulted from the unit.
Mobile stroke units can even supplement existing health care in case of an emergency. Dr. Grotta also recounted how one unit assisted during the aftermath of Hurricane Harvey.
SAN DIEGO – Mobile stroke units are specially equipped ambulance units designed to respond and deliver treatment to stroke patients as swiftly as possible. They are outfitted with a portable CT scanner, a mobile lab, and specialized personnel, including a telemedicine unit to assist with diagnosis. If a patient is experiencing an ischemic stroke, the unit can deliver thrombolytic therapy on the spot, circumventing travel to an emergency department.
But are they cost effective? There are 13 active units in the United States, and they’re not cheap. They cost about $3.5 million to build and operate over 5 years, according to James Grotta, MD, a neurologist with the Memorial Hermann Medical Group and director of stroke research at Memorial Hermann–Texas Medical Center, both in Houston.
In a video interview at the annual meeting of the American Neurological Association, Dr. Grotta described how his group is studying the impact of mobile stroke units on time to treatment and the long-term costs and cost savings associated with them in an ongoing clinical trial that is comparing outcomes in patients eligible for tissue plasminogen activator when treated by a mobile stroke unit versus standard prehospital triage and transport by emergency medical services. The study is comparing outcomes when the mobile stroke unit and emergency medical services are the primary responders on alternating weeks. Primary outcomes include cost-effectiveness, the change in Rankin scale score from baseline to 90 days, and the diagnostic agreement between a vascular neurologist in the mobile stroke unit and a telemedicine vascular neurologist consulted from the unit.
Mobile stroke units can even supplement existing health care in case of an emergency. Dr. Grotta also recounted how one unit assisted during the aftermath of Hurricane Harvey.
AT ANA 2017
Young adult stroke survivors have distinct risk profile
SAN DIEGO – Young adults who have suffered a stroke are at greater risk of a second stroke than other cardiovascular events, at least in the first year. That’s the conclusion drawn from a new analysis of 2013 data drawn from the Nationwide Readmissions Database.
The results suggest that younger adults who have a first-time stroke have a different risk profile than older adults and could require different management to improve long-term outcomes. The incidence of stroke has increased in recent years to the point that this population now accounts for about 10% of all strokes.
The analysis looked at all admissions for ischemic stroke in patients aged 18-45. The researchers found a cumulative risk of rehospitalization of 5.5% at 300 days, compared with 3.6% for cardiovascular disease.
The study can’t explain the association, nor can it prove causation. “Our thought was that the effects of hypertension might take longer to manifest in terms of cardiovascular outcomes as compared to hypercholesterolemia and diabetes,” said Dr. Jin, who is chief resident in the department of neurology at Icahn School of Medicine at Mount Sinai, New York. He presented the research at the annual meeting of the American Neurological Association.
The result sends a clear message for physicians caring for young adults who have experienced a first-time stroke. “They should be rigorously worked up and managed for any disorders in blood sugar and lipid disorders,” Dr. Jin said. Their care is vital because these younger adults have more time to accumulate second, third, or fourth strokes that could dramatically increase the burden of disease. “It’s just a matter of time. Optimizing their secondary prevention is crucial,” Dr. Jin said.
The study included data from 12,392 young adults in the Nationwide Readmissions Database who had suffered a first-time stroke. The researchers identified a higher readmission rate for stroke than cardiovascular events at 90 days (2,913.3 vs. 1,132.4 per 100,000 index hospitalizations). This pattern held when the analysis was restricted to patients who had no cardiovascular risk factors prior to the index hospitalization (2,534.9 vs. 676 per 100,000 index hospitalizations).
At 100 days, the cumulative risks were 3.2% for stroke and 2.5% for cardiovascular events. The risks were 4.3% and 3.2% at 200 days, and 5.5% and 3.6% at 300 days.
A multivariate analysis showed that patients with baseline diabetes were at a heightened risk of cardiovascular events (hazard ratio, 1.49; 95% confidence interval, 1.17-1.88), as were patients with hypercholesterolemia (HR, 1.43; 95% CI, 1.15-1.79) and those with atrial fibrillation or flutter (HR, 3.86; 95% CI, 2.74-5.43). Only diabetes was significantly associated with increased risk for hospitalization for recurrent stroke (HR, 1.5; 95% CI, 1.22-1.84).
Dr. Jin is eager to see if future research might establish a causative link between these risk factors and outcomes. The current work grew out of an administrative data set, but registry data or a prospective study could be more robust.
The study received no external funding. Dr. Jin reported having no financial disclosures.
SAN DIEGO – Young adults who have suffered a stroke are at greater risk of a second stroke than other cardiovascular events, at least in the first year. That’s the conclusion drawn from a new analysis of 2013 data drawn from the Nationwide Readmissions Database.
The results suggest that younger adults who have a first-time stroke have a different risk profile than older adults and could require different management to improve long-term outcomes. The incidence of stroke has increased in recent years to the point that this population now accounts for about 10% of all strokes.
The analysis looked at all admissions for ischemic stroke in patients aged 18-45. The researchers found a cumulative risk of rehospitalization of 5.5% at 300 days, compared with 3.6% for cardiovascular disease.
The study can’t explain the association, nor can it prove causation. “Our thought was that the effects of hypertension might take longer to manifest in terms of cardiovascular outcomes as compared to hypercholesterolemia and diabetes,” said Dr. Jin, who is chief resident in the department of neurology at Icahn School of Medicine at Mount Sinai, New York. He presented the research at the annual meeting of the American Neurological Association.
The result sends a clear message for physicians caring for young adults who have experienced a first-time stroke. “They should be rigorously worked up and managed for any disorders in blood sugar and lipid disorders,” Dr. Jin said. Their care is vital because these younger adults have more time to accumulate second, third, or fourth strokes that could dramatically increase the burden of disease. “It’s just a matter of time. Optimizing their secondary prevention is crucial,” Dr. Jin said.
The study included data from 12,392 young adults in the Nationwide Readmissions Database who had suffered a first-time stroke. The researchers identified a higher readmission rate for stroke than cardiovascular events at 90 days (2,913.3 vs. 1,132.4 per 100,000 index hospitalizations). This pattern held when the analysis was restricted to patients who had no cardiovascular risk factors prior to the index hospitalization (2,534.9 vs. 676 per 100,000 index hospitalizations).
At 100 days, the cumulative risks were 3.2% for stroke and 2.5% for cardiovascular events. The risks were 4.3% and 3.2% at 200 days, and 5.5% and 3.6% at 300 days.
A multivariate analysis showed that patients with baseline diabetes were at a heightened risk of cardiovascular events (hazard ratio, 1.49; 95% confidence interval, 1.17-1.88), as were patients with hypercholesterolemia (HR, 1.43; 95% CI, 1.15-1.79) and those with atrial fibrillation or flutter (HR, 3.86; 95% CI, 2.74-5.43). Only diabetes was significantly associated with increased risk for hospitalization for recurrent stroke (HR, 1.5; 95% CI, 1.22-1.84).
Dr. Jin is eager to see if future research might establish a causative link between these risk factors and outcomes. The current work grew out of an administrative data set, but registry data or a prospective study could be more robust.
The study received no external funding. Dr. Jin reported having no financial disclosures.
SAN DIEGO – Young adults who have suffered a stroke are at greater risk of a second stroke than other cardiovascular events, at least in the first year. That’s the conclusion drawn from a new analysis of 2013 data drawn from the Nationwide Readmissions Database.
The results suggest that younger adults who have a first-time stroke have a different risk profile than older adults and could require different management to improve long-term outcomes. The incidence of stroke has increased in recent years to the point that this population now accounts for about 10% of all strokes.
The analysis looked at all admissions for ischemic stroke in patients aged 18-45. The researchers found a cumulative risk of rehospitalization of 5.5% at 300 days, compared with 3.6% for cardiovascular disease.
The study can’t explain the association, nor can it prove causation. “Our thought was that the effects of hypertension might take longer to manifest in terms of cardiovascular outcomes as compared to hypercholesterolemia and diabetes,” said Dr. Jin, who is chief resident in the department of neurology at Icahn School of Medicine at Mount Sinai, New York. He presented the research at the annual meeting of the American Neurological Association.
The result sends a clear message for physicians caring for young adults who have experienced a first-time stroke. “They should be rigorously worked up and managed for any disorders in blood sugar and lipid disorders,” Dr. Jin said. Their care is vital because these younger adults have more time to accumulate second, third, or fourth strokes that could dramatically increase the burden of disease. “It’s just a matter of time. Optimizing their secondary prevention is crucial,” Dr. Jin said.
The study included data from 12,392 young adults in the Nationwide Readmissions Database who had suffered a first-time stroke. The researchers identified a higher readmission rate for stroke than cardiovascular events at 90 days (2,913.3 vs. 1,132.4 per 100,000 index hospitalizations). This pattern held when the analysis was restricted to patients who had no cardiovascular risk factors prior to the index hospitalization (2,534.9 vs. 676 per 100,000 index hospitalizations).
At 100 days, the cumulative risks were 3.2% for stroke and 2.5% for cardiovascular events. The risks were 4.3% and 3.2% at 200 days, and 5.5% and 3.6% at 300 days.
A multivariate analysis showed that patients with baseline diabetes were at a heightened risk of cardiovascular events (hazard ratio, 1.49; 95% confidence interval, 1.17-1.88), as were patients with hypercholesterolemia (HR, 1.43; 95% CI, 1.15-1.79) and those with atrial fibrillation or flutter (HR, 3.86; 95% CI, 2.74-5.43). Only diabetes was significantly associated with increased risk for hospitalization for recurrent stroke (HR, 1.5; 95% CI, 1.22-1.84).
Dr. Jin is eager to see if future research might establish a causative link between these risk factors and outcomes. The current work grew out of an administrative data set, but registry data or a prospective study could be more robust.
The study received no external funding. Dr. Jin reported having no financial disclosures.
AT ANA 2017
Key clinical point:
Major finding: Hospitalization for cardiovascular disease was associated with baseline diabetes (HR, 1.49) and hypercholesterolemia (HR, 1.43).
Data source: A retrospective analysis of data from the Nationwide Readmissions Database (n = 12,392).
Disclosures: The study received no external funding. Dr. Jin reported having no financial disclosures.
VIDEO: Rethinking deep brain stimulation for depression
SAN DIEGO – Earlier this month, an article in Lancet Psychiatry reported the results of a prospective, randomized, sham-controlled trial that tested deep brain stimulation of the Brodmann area 25 within the subcallosal cingulate white matter in 90 patients with treatment-resistant depression. Unfortunately, the study showed no significant benefit at 6 months.
The approach had shown promise in some previous open-label studies, which prompted the multicenter trial (Lancet Psychiatry. 2017 Oct 4. doi: 10.1016/S2215-0366(17)30371-1).
Although the 6-month results were disappointing, the open-label phase of the study told a different story. At 2 years, 48% of patients in the stimulation group achieved an antidepressant response, higher than what would be expected from treatment as usual in this difficult population.
In this video interview at the annual meeting of the American Neurological Association, Helen Mayberg, MD, one of the study authors and professor of psychiatry, neurology, and radiology at Emory University, Atlanta, discusses these long-term results and their implications, as well as lessons learned and how they might inform future research.
SAN DIEGO – Earlier this month, an article in Lancet Psychiatry reported the results of a prospective, randomized, sham-controlled trial that tested deep brain stimulation of the Brodmann area 25 within the subcallosal cingulate white matter in 90 patients with treatment-resistant depression. Unfortunately, the study showed no significant benefit at 6 months.
The approach had shown promise in some previous open-label studies, which prompted the multicenter trial (Lancet Psychiatry. 2017 Oct 4. doi: 10.1016/S2215-0366(17)30371-1).
Although the 6-month results were disappointing, the open-label phase of the study told a different story. At 2 years, 48% of patients in the stimulation group achieved an antidepressant response, higher than what would be expected from treatment as usual in this difficult population.
In this video interview at the annual meeting of the American Neurological Association, Helen Mayberg, MD, one of the study authors and professor of psychiatry, neurology, and radiology at Emory University, Atlanta, discusses these long-term results and their implications, as well as lessons learned and how they might inform future research.
SAN DIEGO – Earlier this month, an article in Lancet Psychiatry reported the results of a prospective, randomized, sham-controlled trial that tested deep brain stimulation of the Brodmann area 25 within the subcallosal cingulate white matter in 90 patients with treatment-resistant depression. Unfortunately, the study showed no significant benefit at 6 months.
The approach had shown promise in some previous open-label studies, which prompted the multicenter trial (Lancet Psychiatry. 2017 Oct 4. doi: 10.1016/S2215-0366(17)30371-1).
Although the 6-month results were disappointing, the open-label phase of the study told a different story. At 2 years, 48% of patients in the stimulation group achieved an antidepressant response, higher than what would be expected from treatment as usual in this difficult population.
In this video interview at the annual meeting of the American Neurological Association, Helen Mayberg, MD, one of the study authors and professor of psychiatry, neurology, and radiology at Emory University, Atlanta, discusses these long-term results and their implications, as well as lessons learned and how they might inform future research.
AT ANA 2017
Everolimus has long-term efficacy in tuberous sclerosis complex
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
SAN DIEGO – Everolimus reduces the frequency of epileptic seizures in patients with tuberous sclerosis complex (TSC), and its effect appears to gain strength over time. By the end of an extension study, half of patients had at least a 31.7% reduction in seizure frequency at 18 weeks, and that percentage rose to 56.9% at 2 years.
The drug was chosen because it inhibits mammalian target of rapamycin (mTOR), which plays a central role in protein synthesis, cell division, and other vital processes. In patients with TSC, the kinase is overactive, and this leads to abnormalities in brain development. Overall, 85% of TSC patients experience seizures, and 60% are refractory to antiepileptic drugs.
The success of everolimus (Afinitor) is encouraging, and it’s the first epilepsy drug to be chosen for its mechanism of action, David Neal Franz, MD, said in an interview. “It has been used off label, but this study really shows that it has a statistically significant benefit that improves over time. A lot of things are used off label, but most don’t have this kind of class II evidence to support being used,” said Dr. Franz, who presented the study at the annual meeting of the American Neurological Association.
The drug was particularly effective in children, who experienced a greater reduction in seizure frequency over time. That suggests that earlier treatment with everolimus could counter some of the damage in these patients before it becomes entrenched. “We’re planning to do studies to evaluate that. Because if you can avoid intractable epilepsy and its effects on development, there’s the potential to have a very significant benefit for children,” said Dr. Franz, who is a professor of pediatrics and neurology and founding director of the Tuberous Sclerosis Clinic at the University of Cincinnati. He noted that some previous studies showed that early treatment of infantile spasms is associated with lower risk of intellectual disability and autism.
The study enrolled 361 TSC patients with epilepsy across a wide age range (2-65 years). Their epilepsy had remained uncontrolled following treatment with at least six previous drugs. The core phase of the trial lasted 18 weeks, followed by an extension phase in which patients in the placebo group were switched to everolimus with a target dose of 3-15 ng/mL.
The primary efficacy outcome was the change in weekly seizure frequency. The researchers defined a response as a 50% or higher reduction.
In the original pivotal trial (EXIST-3), 15.1% of patients on placebo responded (95% confidence interval, 9.2%-22.8%) at week 18, compared with 28.2% of patients receiving a 3-7 ng/mL dose of everolimus (95% CI, 20.3%-37.3%; P = .0077) and 40% of patients receiving a 9-15 ng/mL dose of everolimus (95% CI, 31.5%-49%; P less than .0001).
The response rate at 18 weeks of treatment when combining both the original everolimus-treated patients and also the group switching over to everolimus in the extension phase was 31% (95% CI, 26.2%-36.1%). By 1 year, 46.6% had responded (95% CI, 40.9%-52.5%), and 57.7% had responded at 2 years (95% CI, 49.7%-65.4%).
The median percentage reduction in seizure frequency rose from 31.7% at week 18 (95% CI, 28.5%-36.1%) to 46.7% at 1 year (95% CI, 40.2%-54.0%) and 56.9% at 2 years (95% CI, 50%-68.4%).
Younger patients experienced greater improvements over time. At 2 years, 76% of 101 patients aged 0-6 years had responded (95% CI, 58.8%-88.2%), compared with 58.5% of patients aged 6-12 years (95% CI, 44.1%-71.9%), 51.1% of patients aged 12-18 years (95% CI, 35.8%-66.3%), and 43% of patients 18 years and older (95% CI, 24.5%-62.8%).
A sensitivity analysis of patients who discontinued the drug and were categorized as nonresponders showed the drug was still associated with a risk reduction of 30.2% at week 18 (95% CI, 25.5%-35.2%), 38.8% at 1 year (95% CI, 33.7%-44.1%), and 41% at 2 years (95% CI, 34.6%-47.7%).
Adverse events declined over time from 76.1% during the first 6 months of treatment to 46.8% at 1 year and 45.2% at 2 years. A total of 40.2% of patients experienced grade III/IV adverse events, and 13% of patients discontinued medication as a result. Another 1.7% experienced pneumonia, and 1.4% experienced stomatitis.
The most concerning side effects noted were tied to infection risk, which was not surprising given that everolimus is an immunosuppressive agent that is also used to prevent organ rejection. “The good thing is that you can hold everolimus when patients get sick or have a fever, and it doesn’t immediately lose efficacy. It binds avidly to mTOR, and so you can often go several weeks off the drug before you see loss of seizure control,” Dr. Franz said.
The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
AT ANA 2017
Key clinical point:
Major finding: The response rate rose from 31% at week 18 to 57.7% at 2 years.
Data source: An extension study of a double-blind, randomized, placebo-controlled trial (n = 361).
Disclosures: The study was funded by Novartis. Dr. Franz has received travel funding and honoraria from Novartis.
Gap in osteoporosis diagnosis and treatment stirs concern
DENVER – A recent study of Medicare recipients who experienced a hip fracture found that just 19% of them had been receiving a bone-active osteoporosis treatment before the fracture occurred. That number reveals an alarming trend of underdiagnosis of osteoporosis.
But that number – from a 2016 study in JAMA Internal Medicine – is just the start. After the fracture, the percentage of women receiving treatment barely changed, rising to just 21% (JAMA Intern Med. 2016 Oct 1;176[10]:1531-8).
This trend of under-diagnosis and treatment of osteoporosis has occurred in spite of the fact that effective therapy exists to reduce future fractures. In fact, a single dose of zoledronic acid has been shown to reduce clinical fractures by 35%, and mortality by 28% over an average 2-year follow-up (N Engl J Med. 2007;357:1799-1809).
“To me, this is really a shame,” Douglas Bauer, MD, professor of medicine at the University of California, San Francisco, said at a session at the annual meeting of the American Society for Bone and Mineral Research that was dedicated to the issue.
It remains unclear why the fracture rate declined despite low levels of diagnosis and treatment. Some researchers, such as Bo Abrahamsen, MD, PhD, suggest there is a population effect. At the ASBMR annual meeting, Dr. Abrahamsen of the University of Southern Denmark, Odense, noted that in the western world, women born in the 1930s appear to be less prone to fractures than other birth cohorts, and it could be that this group contributed to the decline in fracture rates. A Danish study, he said, seems to confirm this idea. As other birth cohorts age, the numbers could well get worse.
And that’s worrying, because a gap in treatment and diagnosis of osteoporosis could lead to an epidemic of new fractures. “We need to address this crisis in health care for a very preventable disease,” Meryl LeBoff, MD, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women’s Hospital, Boston, said in an interview.
There are several likely causes of declining treatment and diagnosis rates. In 2003, a report surfaced that osteonecrosis of the jaw occurred in cancer patients taking bisphosphonates to prevent metastasis to bone. Those patients received doses that were far higher than the typical osteoporosis patient, but the reports spooked patients. In 2005, researchers pinned another rare side effect on bisphosphonates – atypical femur fractures.
Other factors contributed. In 2007, the Centers for Medicare & Medicaid Services cut the reimbursement rate for bone densitometry (DXA) testing, which has led to a drop in the number of tests, from a peak of 17.9% of women over age 65 years having been tested in 2009 to 14.8% in 2014. That has complicated efforts to diagnose osteoporosis, and may be affecting patients’ willingness to undergo therapy. A patient may go to the hospital for a hip fracture, but without a bone density test to raise concerns, she may write the fracture off as an accident. A DXA test that returns an abnormal value can change that. “If you have low BMD and a fracture, you have a worse prognosis and a higher risk of the next fracture. It’s much easier to convince patients [to begin therapy],” said John Carey, MD, a rheumatologist at Galway (Ireland) University Hospitals and president of the International Society for Clinical Densitometry.
Others emphasized the need to get DXA reimbursement raised, at least to a point where physicians can break even on the test. “Unfortunately, what’s happening is that as DXA reimbursement goes down, physicians are investing less in the education of their staff according to current guidelines,” Dr. Lewiecki said. He noted that there is draft legislation in Congress to raise DXA reimbursement (H.R. 1898), although it is currently in committee.
The forces that create the treatment and diagnostic gap aren’t simple, and no single strategy is likely to fix the problem. A number have been proposed.
FLS programs seek to quickly identify and provide treatment and monitoring for individuals who are at high risk for additional fractures. The programs identify patients who have suffered a fragility fracture and place them into a coordinated care model. For example, if a radiologist identified a patient of concern, she can be immediately referred to the FLS for quick follow-up, to include bone density scans and other steps to ensure proper diagnosis and treatment. In the absence of an FLS, it could be months before a patient is seen again, if a radiologist refers her at all. “You lose patients. But if they are tied into a coordination of care model, the patient is brought in immediately and they get the attention and awareness. They’re not just lost,” said Debbie Zeldow, executive director of the National Bone Health Alliance (NBHA).
Despite their effectiveness, FLS programs could be a tough sell for the upfront investment they require. To help organizations determine the cost-effectiveness of an FLS, the National Bone Health Alliance has developed a return on investment calculator.
And in fact, FLS programs are gaining traction, according to Ms. Zeldow. NBHA has posted a variety of resources for establishing an FLS on its website, which contains webinars and other resources, including the text of patient flyers produced by Kaiser Permanente translated into many languages. “There’s been a huge jump in interest in implementation. I’m getting calls on a daily basis from sites that want to implement an FLS. People are being pinged for readmission, and they’re looking for ways for their hospital or practice to improve outcomes. It’s definitely a way for hospitals to differentiate themselves around care,” Ms. Zeldow said in an interview.
FLS programs reduce secondary fractures, but the ultimate goal is to catch osteoporosis earlier and prevent even first-time fractures. That will require better communication with primary care providers, who bear the brunt of osteoporosis diagnosis and care.
“We need to do a better job of reducing barriers for primary care doctors, to try to minimize unnecessary treatment complexity, and address the fact that this is one of the many prevention issues that physicians are asked to manage, and all that in an increasingly time-constrained world,” Dr. Bauer said.
With that goal in mind, the American College of Physicians released new guidelines in May (Ann Intern Med. 2017;166[11]:818-39). They were intended to identify first-line therapies and simplify matters for primary care physicians, but they drew the ire of many endocrinologists for being too general. NBHA has formed an ACP guideline working group that aims to refine those guidelines. The committee is drafting a statement and a document for patients to help clarify the guidelines, particularly with respect to high-risk patients. The committee also seeks to avoid any rancor. “We’ve made a concerted effort to include primary care doctors, to make sure there’s not a disconnect between experts and general practitioners. We want to make sure it’s a useful tool and we’re not just bashing the guidelines,” Ms. Zeldow said.
Another way to help overburdened primary care providers is to provide training for physicians, especially in underserved areas. The National Osteoporosis Foundation’s TeleECHO program is a remote training service that can help interested local providers elevate their knowledge so they can become a local osteoporosis expert. “Patients can get better care, at more convenience and at lower cost, rather than having to travel to a specialist center far away,” Dr. Lewiecki said.
Patient concerns about side effects, the changing health care climate, and the challenges facing primary care providers add up to difficult environment for countering the reductions in diagnosis and treatment of osteoporosis, but Dr. Lewiecki is hopeful. “Fracture liaison services combined with better education of health care providers through new educational methods I think have great promise. It’s just a matter of getting those things online,” he said.
Dr. Carey has been a speaker for Roche, Pfizer, and AbbVie. Dr. Lewiecki has consulted for Amgen. Dr. Leder has received funding from Lilly and Amgen, and has been a consultant for Lilly, Amgen, and Radius. Dr. Bauer and Ms. Zeldow reported having no financial disclosures.
DENVER – A recent study of Medicare recipients who experienced a hip fracture found that just 19% of them had been receiving a bone-active osteoporosis treatment before the fracture occurred. That number reveals an alarming trend of underdiagnosis of osteoporosis.
But that number – from a 2016 study in JAMA Internal Medicine – is just the start. After the fracture, the percentage of women receiving treatment barely changed, rising to just 21% (JAMA Intern Med. 2016 Oct 1;176[10]:1531-8).
This trend of under-diagnosis and treatment of osteoporosis has occurred in spite of the fact that effective therapy exists to reduce future fractures. In fact, a single dose of zoledronic acid has been shown to reduce clinical fractures by 35%, and mortality by 28% over an average 2-year follow-up (N Engl J Med. 2007;357:1799-1809).
“To me, this is really a shame,” Douglas Bauer, MD, professor of medicine at the University of California, San Francisco, said at a session at the annual meeting of the American Society for Bone and Mineral Research that was dedicated to the issue.
It remains unclear why the fracture rate declined despite low levels of diagnosis and treatment. Some researchers, such as Bo Abrahamsen, MD, PhD, suggest there is a population effect. At the ASBMR annual meeting, Dr. Abrahamsen of the University of Southern Denmark, Odense, noted that in the western world, women born in the 1930s appear to be less prone to fractures than other birth cohorts, and it could be that this group contributed to the decline in fracture rates. A Danish study, he said, seems to confirm this idea. As other birth cohorts age, the numbers could well get worse.
And that’s worrying, because a gap in treatment and diagnosis of osteoporosis could lead to an epidemic of new fractures. “We need to address this crisis in health care for a very preventable disease,” Meryl LeBoff, MD, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women’s Hospital, Boston, said in an interview.
There are several likely causes of declining treatment and diagnosis rates. In 2003, a report surfaced that osteonecrosis of the jaw occurred in cancer patients taking bisphosphonates to prevent metastasis to bone. Those patients received doses that were far higher than the typical osteoporosis patient, but the reports spooked patients. In 2005, researchers pinned another rare side effect on bisphosphonates – atypical femur fractures.
Other factors contributed. In 2007, the Centers for Medicare & Medicaid Services cut the reimbursement rate for bone densitometry (DXA) testing, which has led to a drop in the number of tests, from a peak of 17.9% of women over age 65 years having been tested in 2009 to 14.8% in 2014. That has complicated efforts to diagnose osteoporosis, and may be affecting patients’ willingness to undergo therapy. A patient may go to the hospital for a hip fracture, but without a bone density test to raise concerns, she may write the fracture off as an accident. A DXA test that returns an abnormal value can change that. “If you have low BMD and a fracture, you have a worse prognosis and a higher risk of the next fracture. It’s much easier to convince patients [to begin therapy],” said John Carey, MD, a rheumatologist at Galway (Ireland) University Hospitals and president of the International Society for Clinical Densitometry.
Others emphasized the need to get DXA reimbursement raised, at least to a point where physicians can break even on the test. “Unfortunately, what’s happening is that as DXA reimbursement goes down, physicians are investing less in the education of their staff according to current guidelines,” Dr. Lewiecki said. He noted that there is draft legislation in Congress to raise DXA reimbursement (H.R. 1898), although it is currently in committee.
The forces that create the treatment and diagnostic gap aren’t simple, and no single strategy is likely to fix the problem. A number have been proposed.
FLS programs seek to quickly identify and provide treatment and monitoring for individuals who are at high risk for additional fractures. The programs identify patients who have suffered a fragility fracture and place them into a coordinated care model. For example, if a radiologist identified a patient of concern, she can be immediately referred to the FLS for quick follow-up, to include bone density scans and other steps to ensure proper diagnosis and treatment. In the absence of an FLS, it could be months before a patient is seen again, if a radiologist refers her at all. “You lose patients. But if they are tied into a coordination of care model, the patient is brought in immediately and they get the attention and awareness. They’re not just lost,” said Debbie Zeldow, executive director of the National Bone Health Alliance (NBHA).
Despite their effectiveness, FLS programs could be a tough sell for the upfront investment they require. To help organizations determine the cost-effectiveness of an FLS, the National Bone Health Alliance has developed a return on investment calculator.
And in fact, FLS programs are gaining traction, according to Ms. Zeldow. NBHA has posted a variety of resources for establishing an FLS on its website, which contains webinars and other resources, including the text of patient flyers produced by Kaiser Permanente translated into many languages. “There’s been a huge jump in interest in implementation. I’m getting calls on a daily basis from sites that want to implement an FLS. People are being pinged for readmission, and they’re looking for ways for their hospital or practice to improve outcomes. It’s definitely a way for hospitals to differentiate themselves around care,” Ms. Zeldow said in an interview.
FLS programs reduce secondary fractures, but the ultimate goal is to catch osteoporosis earlier and prevent even first-time fractures. That will require better communication with primary care providers, who bear the brunt of osteoporosis diagnosis and care.
“We need to do a better job of reducing barriers for primary care doctors, to try to minimize unnecessary treatment complexity, and address the fact that this is one of the many prevention issues that physicians are asked to manage, and all that in an increasingly time-constrained world,” Dr. Bauer said.
With that goal in mind, the American College of Physicians released new guidelines in May (Ann Intern Med. 2017;166[11]:818-39). They were intended to identify first-line therapies and simplify matters for primary care physicians, but they drew the ire of many endocrinologists for being too general. NBHA has formed an ACP guideline working group that aims to refine those guidelines. The committee is drafting a statement and a document for patients to help clarify the guidelines, particularly with respect to high-risk patients. The committee also seeks to avoid any rancor. “We’ve made a concerted effort to include primary care doctors, to make sure there’s not a disconnect between experts and general practitioners. We want to make sure it’s a useful tool and we’re not just bashing the guidelines,” Ms. Zeldow said.
Another way to help overburdened primary care providers is to provide training for physicians, especially in underserved areas. The National Osteoporosis Foundation’s TeleECHO program is a remote training service that can help interested local providers elevate their knowledge so they can become a local osteoporosis expert. “Patients can get better care, at more convenience and at lower cost, rather than having to travel to a specialist center far away,” Dr. Lewiecki said.
Patient concerns about side effects, the changing health care climate, and the challenges facing primary care providers add up to difficult environment for countering the reductions in diagnosis and treatment of osteoporosis, but Dr. Lewiecki is hopeful. “Fracture liaison services combined with better education of health care providers through new educational methods I think have great promise. It’s just a matter of getting those things online,” he said.
Dr. Carey has been a speaker for Roche, Pfizer, and AbbVie. Dr. Lewiecki has consulted for Amgen. Dr. Leder has received funding from Lilly and Amgen, and has been a consultant for Lilly, Amgen, and Radius. Dr. Bauer and Ms. Zeldow reported having no financial disclosures.
DENVER – A recent study of Medicare recipients who experienced a hip fracture found that just 19% of them had been receiving a bone-active osteoporosis treatment before the fracture occurred. That number reveals an alarming trend of underdiagnosis of osteoporosis.
But that number – from a 2016 study in JAMA Internal Medicine – is just the start. After the fracture, the percentage of women receiving treatment barely changed, rising to just 21% (JAMA Intern Med. 2016 Oct 1;176[10]:1531-8).
This trend of under-diagnosis and treatment of osteoporosis has occurred in spite of the fact that effective therapy exists to reduce future fractures. In fact, a single dose of zoledronic acid has been shown to reduce clinical fractures by 35%, and mortality by 28% over an average 2-year follow-up (N Engl J Med. 2007;357:1799-1809).
“To me, this is really a shame,” Douglas Bauer, MD, professor of medicine at the University of California, San Francisco, said at a session at the annual meeting of the American Society for Bone and Mineral Research that was dedicated to the issue.
It remains unclear why the fracture rate declined despite low levels of diagnosis and treatment. Some researchers, such as Bo Abrahamsen, MD, PhD, suggest there is a population effect. At the ASBMR annual meeting, Dr. Abrahamsen of the University of Southern Denmark, Odense, noted that in the western world, women born in the 1930s appear to be less prone to fractures than other birth cohorts, and it could be that this group contributed to the decline in fracture rates. A Danish study, he said, seems to confirm this idea. As other birth cohorts age, the numbers could well get worse.
And that’s worrying, because a gap in treatment and diagnosis of osteoporosis could lead to an epidemic of new fractures. “We need to address this crisis in health care for a very preventable disease,” Meryl LeBoff, MD, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women’s Hospital, Boston, said in an interview.
There are several likely causes of declining treatment and diagnosis rates. In 2003, a report surfaced that osteonecrosis of the jaw occurred in cancer patients taking bisphosphonates to prevent metastasis to bone. Those patients received doses that were far higher than the typical osteoporosis patient, but the reports spooked patients. In 2005, researchers pinned another rare side effect on bisphosphonates – atypical femur fractures.
Other factors contributed. In 2007, the Centers for Medicare & Medicaid Services cut the reimbursement rate for bone densitometry (DXA) testing, which has led to a drop in the number of tests, from a peak of 17.9% of women over age 65 years having been tested in 2009 to 14.8% in 2014. That has complicated efforts to diagnose osteoporosis, and may be affecting patients’ willingness to undergo therapy. A patient may go to the hospital for a hip fracture, but without a bone density test to raise concerns, she may write the fracture off as an accident. A DXA test that returns an abnormal value can change that. “If you have low BMD and a fracture, you have a worse prognosis and a higher risk of the next fracture. It’s much easier to convince patients [to begin therapy],” said John Carey, MD, a rheumatologist at Galway (Ireland) University Hospitals and president of the International Society for Clinical Densitometry.
Others emphasized the need to get DXA reimbursement raised, at least to a point where physicians can break even on the test. “Unfortunately, what’s happening is that as DXA reimbursement goes down, physicians are investing less in the education of their staff according to current guidelines,” Dr. Lewiecki said. He noted that there is draft legislation in Congress to raise DXA reimbursement (H.R. 1898), although it is currently in committee.
The forces that create the treatment and diagnostic gap aren’t simple, and no single strategy is likely to fix the problem. A number have been proposed.
FLS programs seek to quickly identify and provide treatment and monitoring for individuals who are at high risk for additional fractures. The programs identify patients who have suffered a fragility fracture and place them into a coordinated care model. For example, if a radiologist identified a patient of concern, she can be immediately referred to the FLS for quick follow-up, to include bone density scans and other steps to ensure proper diagnosis and treatment. In the absence of an FLS, it could be months before a patient is seen again, if a radiologist refers her at all. “You lose patients. But if they are tied into a coordination of care model, the patient is brought in immediately and they get the attention and awareness. They’re not just lost,” said Debbie Zeldow, executive director of the National Bone Health Alliance (NBHA).
Despite their effectiveness, FLS programs could be a tough sell for the upfront investment they require. To help organizations determine the cost-effectiveness of an FLS, the National Bone Health Alliance has developed a return on investment calculator.
And in fact, FLS programs are gaining traction, according to Ms. Zeldow. NBHA has posted a variety of resources for establishing an FLS on its website, which contains webinars and other resources, including the text of patient flyers produced by Kaiser Permanente translated into many languages. “There’s been a huge jump in interest in implementation. I’m getting calls on a daily basis from sites that want to implement an FLS. People are being pinged for readmission, and they’re looking for ways for their hospital or practice to improve outcomes. It’s definitely a way for hospitals to differentiate themselves around care,” Ms. Zeldow said in an interview.
FLS programs reduce secondary fractures, but the ultimate goal is to catch osteoporosis earlier and prevent even first-time fractures. That will require better communication with primary care providers, who bear the brunt of osteoporosis diagnosis and care.
“We need to do a better job of reducing barriers for primary care doctors, to try to minimize unnecessary treatment complexity, and address the fact that this is one of the many prevention issues that physicians are asked to manage, and all that in an increasingly time-constrained world,” Dr. Bauer said.
With that goal in mind, the American College of Physicians released new guidelines in May (Ann Intern Med. 2017;166[11]:818-39). They were intended to identify first-line therapies and simplify matters for primary care physicians, but they drew the ire of many endocrinologists for being too general. NBHA has formed an ACP guideline working group that aims to refine those guidelines. The committee is drafting a statement and a document for patients to help clarify the guidelines, particularly with respect to high-risk patients. The committee also seeks to avoid any rancor. “We’ve made a concerted effort to include primary care doctors, to make sure there’s not a disconnect between experts and general practitioners. We want to make sure it’s a useful tool and we’re not just bashing the guidelines,” Ms. Zeldow said.
Another way to help overburdened primary care providers is to provide training for physicians, especially in underserved areas. The National Osteoporosis Foundation’s TeleECHO program is a remote training service that can help interested local providers elevate their knowledge so they can become a local osteoporosis expert. “Patients can get better care, at more convenience and at lower cost, rather than having to travel to a specialist center far away,” Dr. Lewiecki said.
Patient concerns about side effects, the changing health care climate, and the challenges facing primary care providers add up to difficult environment for countering the reductions in diagnosis and treatment of osteoporosis, but Dr. Lewiecki is hopeful. “Fracture liaison services combined with better education of health care providers through new educational methods I think have great promise. It’s just a matter of getting those things online,” he said.
Dr. Carey has been a speaker for Roche, Pfizer, and AbbVie. Dr. Lewiecki has consulted for Amgen. Dr. Leder has received funding from Lilly and Amgen, and has been a consultant for Lilly, Amgen, and Radius. Dr. Bauer and Ms. Zeldow reported having no financial disclosures.
AT ASBMR
Old and newer systemic therapies benefit patients with chronic eczema
Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.
Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
Older systemic medications
These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.
Mycophenolate mofetil is useful when the adverse event profiles of azathioprine, methotrexate, and cyclosporin A eliminate them from consideration, but it tends to confer slower improvement and has less efficacy overall.
Cyclosporin A led to successful outcomes in 77% of patients and mild improvement in 16% of patients in one trial, with milder side effects than those commonly seen in transplant patients. There was no increased risk of nephrotoxicity or hypertension over 6 months of treatment. The drug is useful for short-term control of flares and in contact dermatitis when corticosteroids are contraindicated, according to Dr. Fowler of the department of dermatology and director of occupational dermatitis at the University of Louisville (Ky.). It is the only drug other than corticosteroids that offers rapid improvement.
Newer drug options
One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.
The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.
The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.
The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.
Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.
Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.
Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
Older systemic medications
These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.
Mycophenolate mofetil is useful when the adverse event profiles of azathioprine, methotrexate, and cyclosporin A eliminate them from consideration, but it tends to confer slower improvement and has less efficacy overall.
Cyclosporin A led to successful outcomes in 77% of patients and mild improvement in 16% of patients in one trial, with milder side effects than those commonly seen in transplant patients. There was no increased risk of nephrotoxicity or hypertension over 6 months of treatment. The drug is useful for short-term control of flares and in contact dermatitis when corticosteroids are contraindicated, according to Dr. Fowler of the department of dermatology and director of occupational dermatitis at the University of Louisville (Ky.). It is the only drug other than corticosteroids that offers rapid improvement.
Newer drug options
One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.
The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.
The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.
The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.
Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.
Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.
Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
Older systemic medications
These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.
Mycophenolate mofetil is useful when the adverse event profiles of azathioprine, methotrexate, and cyclosporin A eliminate them from consideration, but it tends to confer slower improvement and has less efficacy overall.
Cyclosporin A led to successful outcomes in 77% of patients and mild improvement in 16% of patients in one trial, with milder side effects than those commonly seen in transplant patients. There was no increased risk of nephrotoxicity or hypertension over 6 months of treatment. The drug is useful for short-term control of flares and in contact dermatitis when corticosteroids are contraindicated, according to Dr. Fowler of the department of dermatology and director of occupational dermatitis at the University of Louisville (Ky.). It is the only drug other than corticosteroids that offers rapid improvement.
Newer drug options
One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.
The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.
The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.
The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.
Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.
EXPERT ANALYSIS FROM THE COASTAL DERMATOLOGY SYMPOSIUM