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U.S. mammogram update sparks concern, reignites debates
, while also renewing debates about the timing of these tests and the screening approaches used.
The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.
The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.
The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.
For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.
However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.
A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.
“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”
For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
The ongoing debates
Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.
The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.
When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”
At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”
When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.
A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.
“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.
Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.
“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”
While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.
Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.
As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.
The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.
The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.
In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”
Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
What’s next?
Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.
According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.
Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.
For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.
When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.
As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.
However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.
Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”
A version of this article first appeared on Medscape.com.
, while also renewing debates about the timing of these tests and the screening approaches used.
The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.
The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.
The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.
For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.
However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.
A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.
“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”
For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
The ongoing debates
Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.
The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.
When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”
At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”
When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.
A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.
“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.
Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.
“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”
While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.
Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.
As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.
The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.
The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.
In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”
Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
What’s next?
Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.
According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.
Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.
For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.
When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.
As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.
However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.
Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”
A version of this article first appeared on Medscape.com.
, while also renewing debates about the timing of these tests and the screening approaches used.
The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.
The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.
The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.
For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.
However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.
A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.
“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”
For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
The ongoing debates
Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.
The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.
When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”
At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”
When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.
A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.
“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.
Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.
“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”
While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.
Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.
As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.
The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.
The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.
In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”
Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
What’s next?
Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.
According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.
Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.
For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.
When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.
As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.
However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.
Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”
A version of this article first appeared on Medscape.com.
Humira biosimilars: Five things to know
The best-selling drug Humira (adalimumab) now faces competition in the United States after a 20-year monopoly. The first adalimumab biosimilar, Amjevita, launched in the United States on January 31, and in July, seven additional biosimilars became available. These drugs have the potential to lower prescription drug prices, but when and by how much remains to be seen.
Here’s what you need to know about adalimumab biosimilars.
What Humira biosimilars are now available?
Eight different biosimilars have launched in 2023 with discounts as large at 85% from Humira’s list price of $6,922. A few companies also offer two price points.
Three of these biosimilars – Hadlima, Hyrimoz, and Yuflyma – are available in high concentration formulations. This high concentration formulation makes up 85% of Humira prescriptions, according to a report from Goodroot, a collection of companies focused on lowering health care costs.
Cyltezo is currently the only adalimumab biosimilar with an interchangeability designation, meaning that a pharmacist can substitute the biosimilar for an equivalent Humira prescription without the intervention of a clinician. A total of 47 states allow for these substitutions without prior approval from a clinician, according to Goodroot, and the clinician must be notified of the switch within a certain time frame. A total of 40 states require that patients be notified of the switch before substitution.
However, it’s not clear if this interchangeability designation will prove an advantage for Cyltezo, as it is interchangeable with the lower concentration version of Humira that makes up just 15% of prescriptions.
Most of the companies behind these biosimilars are pursuing interchangeability designations for their drugs, except for Fresenius Kabi (Idacio) and Coherus (Yusimry).
A ninth biosimilar, Pfizer’s adalimumab-afzb (Abrilada), is not yet on the market and is currently awaiting an approval decision from the Food and Drug Administration to add an interchangeability designation to its prior approval for a low-concentration formulation.
Why are they priced differently?
The two price points offer different deals to payers. Pharmacy benefit managers make confidential agreements with drug manufacturers to get a discount – called a rebate – to get the drug on the PBM’s formulary. The PBM keeps a portion of that rebate, and the rest is passed on to the insurance company and patients. Biosimilars at a higher price point will likely offer larger rebates. Biosimilars offered at lower price points incorporate this discount up front in their list pricing and likely will not offer large rebates.
Will biosimilars be covered by payers?
Currently, biosimilars are being offered on formularies at parity with Humira, meaning they are on the same tier. The PBM companies OptumRx and Cigna Group’s Express Scripts will offer Amjevita (at both price points), Cyltezo, and Hyrimoz (at both price points).
“This decision allows our clients flexibility to provide access to the lower list price, so members in high-deductible plans and benefit designs with coinsurance can experience lower out-of-pocket costs,” said OptumRx spokesperson Isaac Sorensen in an email.
Mark Cuban Cost Plus Drug Company, which uses a direct-to-consumer model, will offer Yusimry for $567.27 on its website. SmithRx, a PBM based in San Francisco, announced it would partner with Cost Plus Drugs to offer Yusimry, adding that SmithRx members can use their insurance benefits to further reduce out-of-pocket costs. RxPreferred, another PBM, will also offer Yusimry through its partnership with Cuban’s company.
The news website Formulary Watch previously reported that CVS Caremark, another of the biggest PBMs, will be offering Amjevita, but as a nonpreferred brand, while Humira remains the preferred brand. CVS Caremark did not respond to a request for comment.
Will patients pay less?
Biosimilars have been touted as a potential solution to lower spending on biologic drugs, but it’s unknown if patients will ultimately benefit with lower out-of-pocket costs. It’s “impossible to predict” if the discount that third-party payers pay will be passed on to consumers, said Mark Fendrick, MD, who directs the University of Michigan Center for Value-based Insurance Design in Ann Arbor.
Generally, a consumer’s copay is a percentage of a drug’s list price, so it stands to reason that a low drug price would result in lower out-of-pocket payments. While this is mostly true, Humira has a successful copay assistance program to lower prescription costs for consumers. According to a 2022 IQVIA report, 82% of commercial prescriptions cost patients less than $10 for Humira because of this program.
To appeal to patients, biosimilar companies will need to offer similar savings, Dr. Fendrick added. “There will be some discontent if patients are actually asked to pay more out-of-pocket for a less expensive drug,” he said.
All eight companies behind these biosimilars are offering or will be launching copay saving programs, many which advertise copays as low as $0 per month for eligible patients.
How will Humira respond?
Marta Wosińska, PhD, a health care economist at the Brookings Institute, Washington, predicts payers will use these lower biosimilar prices to negotiate better deals with AbbVie, Humira’s manufacturer. “We have a lot of players coming into [the market] right now, so the competition is really fierce,” she said. In response, AbbVie will need to increase rebates on Humira and/or lower its price to compete with these biosimilars.
“The ball is in AbbVie’s court,” she said. “If [the company] is not willing to drop price sufficiently, then payers will start switching to biosimilars.”
Dr. Fendrick reported past financial relationships and consulting arrangements with AbbVie, Amgen, Arnold Ventures, Bayer, CareFirst, BlueCross BlueShield, and many other companies. Dr. Wosińska has received funding from Arnold Ventures and serves as an expert witness on antitrust cases involving generic medication.
A version of this article first appeared on Medscape.com.
The best-selling drug Humira (adalimumab) now faces competition in the United States after a 20-year monopoly. The first adalimumab biosimilar, Amjevita, launched in the United States on January 31, and in July, seven additional biosimilars became available. These drugs have the potential to lower prescription drug prices, but when and by how much remains to be seen.
Here’s what you need to know about adalimumab biosimilars.
What Humira biosimilars are now available?
Eight different biosimilars have launched in 2023 with discounts as large at 85% from Humira’s list price of $6,922. A few companies also offer two price points.
Three of these biosimilars – Hadlima, Hyrimoz, and Yuflyma – are available in high concentration formulations. This high concentration formulation makes up 85% of Humira prescriptions, according to a report from Goodroot, a collection of companies focused on lowering health care costs.
Cyltezo is currently the only adalimumab biosimilar with an interchangeability designation, meaning that a pharmacist can substitute the biosimilar for an equivalent Humira prescription without the intervention of a clinician. A total of 47 states allow for these substitutions without prior approval from a clinician, according to Goodroot, and the clinician must be notified of the switch within a certain time frame. A total of 40 states require that patients be notified of the switch before substitution.
However, it’s not clear if this interchangeability designation will prove an advantage for Cyltezo, as it is interchangeable with the lower concentration version of Humira that makes up just 15% of prescriptions.
Most of the companies behind these biosimilars are pursuing interchangeability designations for their drugs, except for Fresenius Kabi (Idacio) and Coherus (Yusimry).
A ninth biosimilar, Pfizer’s adalimumab-afzb (Abrilada), is not yet on the market and is currently awaiting an approval decision from the Food and Drug Administration to add an interchangeability designation to its prior approval for a low-concentration formulation.
Why are they priced differently?
The two price points offer different deals to payers. Pharmacy benefit managers make confidential agreements with drug manufacturers to get a discount – called a rebate – to get the drug on the PBM’s formulary. The PBM keeps a portion of that rebate, and the rest is passed on to the insurance company and patients. Biosimilars at a higher price point will likely offer larger rebates. Biosimilars offered at lower price points incorporate this discount up front in their list pricing and likely will not offer large rebates.
Will biosimilars be covered by payers?
Currently, biosimilars are being offered on formularies at parity with Humira, meaning they are on the same tier. The PBM companies OptumRx and Cigna Group’s Express Scripts will offer Amjevita (at both price points), Cyltezo, and Hyrimoz (at both price points).
“This decision allows our clients flexibility to provide access to the lower list price, so members in high-deductible plans and benefit designs with coinsurance can experience lower out-of-pocket costs,” said OptumRx spokesperson Isaac Sorensen in an email.
Mark Cuban Cost Plus Drug Company, which uses a direct-to-consumer model, will offer Yusimry for $567.27 on its website. SmithRx, a PBM based in San Francisco, announced it would partner with Cost Plus Drugs to offer Yusimry, adding that SmithRx members can use their insurance benefits to further reduce out-of-pocket costs. RxPreferred, another PBM, will also offer Yusimry through its partnership with Cuban’s company.
The news website Formulary Watch previously reported that CVS Caremark, another of the biggest PBMs, will be offering Amjevita, but as a nonpreferred brand, while Humira remains the preferred brand. CVS Caremark did not respond to a request for comment.
Will patients pay less?
Biosimilars have been touted as a potential solution to lower spending on biologic drugs, but it’s unknown if patients will ultimately benefit with lower out-of-pocket costs. It’s “impossible to predict” if the discount that third-party payers pay will be passed on to consumers, said Mark Fendrick, MD, who directs the University of Michigan Center for Value-based Insurance Design in Ann Arbor.
Generally, a consumer’s copay is a percentage of a drug’s list price, so it stands to reason that a low drug price would result in lower out-of-pocket payments. While this is mostly true, Humira has a successful copay assistance program to lower prescription costs for consumers. According to a 2022 IQVIA report, 82% of commercial prescriptions cost patients less than $10 for Humira because of this program.
To appeal to patients, biosimilar companies will need to offer similar savings, Dr. Fendrick added. “There will be some discontent if patients are actually asked to pay more out-of-pocket for a less expensive drug,” he said.
All eight companies behind these biosimilars are offering or will be launching copay saving programs, many which advertise copays as low as $0 per month for eligible patients.
How will Humira respond?
Marta Wosińska, PhD, a health care economist at the Brookings Institute, Washington, predicts payers will use these lower biosimilar prices to negotiate better deals with AbbVie, Humira’s manufacturer. “We have a lot of players coming into [the market] right now, so the competition is really fierce,” she said. In response, AbbVie will need to increase rebates on Humira and/or lower its price to compete with these biosimilars.
“The ball is in AbbVie’s court,” she said. “If [the company] is not willing to drop price sufficiently, then payers will start switching to biosimilars.”
Dr. Fendrick reported past financial relationships and consulting arrangements with AbbVie, Amgen, Arnold Ventures, Bayer, CareFirst, BlueCross BlueShield, and many other companies. Dr. Wosińska has received funding from Arnold Ventures and serves as an expert witness on antitrust cases involving generic medication.
A version of this article first appeared on Medscape.com.
The best-selling drug Humira (adalimumab) now faces competition in the United States after a 20-year monopoly. The first adalimumab biosimilar, Amjevita, launched in the United States on January 31, and in July, seven additional biosimilars became available. These drugs have the potential to lower prescription drug prices, but when and by how much remains to be seen.
Here’s what you need to know about adalimumab biosimilars.
What Humira biosimilars are now available?
Eight different biosimilars have launched in 2023 with discounts as large at 85% from Humira’s list price of $6,922. A few companies also offer two price points.
Three of these biosimilars – Hadlima, Hyrimoz, and Yuflyma – are available in high concentration formulations. This high concentration formulation makes up 85% of Humira prescriptions, according to a report from Goodroot, a collection of companies focused on lowering health care costs.
Cyltezo is currently the only adalimumab biosimilar with an interchangeability designation, meaning that a pharmacist can substitute the biosimilar for an equivalent Humira prescription without the intervention of a clinician. A total of 47 states allow for these substitutions without prior approval from a clinician, according to Goodroot, and the clinician must be notified of the switch within a certain time frame. A total of 40 states require that patients be notified of the switch before substitution.
However, it’s not clear if this interchangeability designation will prove an advantage for Cyltezo, as it is interchangeable with the lower concentration version of Humira that makes up just 15% of prescriptions.
Most of the companies behind these biosimilars are pursuing interchangeability designations for their drugs, except for Fresenius Kabi (Idacio) and Coherus (Yusimry).
A ninth biosimilar, Pfizer’s adalimumab-afzb (Abrilada), is not yet on the market and is currently awaiting an approval decision from the Food and Drug Administration to add an interchangeability designation to its prior approval for a low-concentration formulation.
Why are they priced differently?
The two price points offer different deals to payers. Pharmacy benefit managers make confidential agreements with drug manufacturers to get a discount – called a rebate – to get the drug on the PBM’s formulary. The PBM keeps a portion of that rebate, and the rest is passed on to the insurance company and patients. Biosimilars at a higher price point will likely offer larger rebates. Biosimilars offered at lower price points incorporate this discount up front in their list pricing and likely will not offer large rebates.
Will biosimilars be covered by payers?
Currently, biosimilars are being offered on formularies at parity with Humira, meaning they are on the same tier. The PBM companies OptumRx and Cigna Group’s Express Scripts will offer Amjevita (at both price points), Cyltezo, and Hyrimoz (at both price points).
“This decision allows our clients flexibility to provide access to the lower list price, so members in high-deductible plans and benefit designs with coinsurance can experience lower out-of-pocket costs,” said OptumRx spokesperson Isaac Sorensen in an email.
Mark Cuban Cost Plus Drug Company, which uses a direct-to-consumer model, will offer Yusimry for $567.27 on its website. SmithRx, a PBM based in San Francisco, announced it would partner with Cost Plus Drugs to offer Yusimry, adding that SmithRx members can use their insurance benefits to further reduce out-of-pocket costs. RxPreferred, another PBM, will also offer Yusimry through its partnership with Cuban’s company.
The news website Formulary Watch previously reported that CVS Caremark, another of the biggest PBMs, will be offering Amjevita, but as a nonpreferred brand, while Humira remains the preferred brand. CVS Caremark did not respond to a request for comment.
Will patients pay less?
Biosimilars have been touted as a potential solution to lower spending on biologic drugs, but it’s unknown if patients will ultimately benefit with lower out-of-pocket costs. It’s “impossible to predict” if the discount that third-party payers pay will be passed on to consumers, said Mark Fendrick, MD, who directs the University of Michigan Center for Value-based Insurance Design in Ann Arbor.
Generally, a consumer’s copay is a percentage of a drug’s list price, so it stands to reason that a low drug price would result in lower out-of-pocket payments. While this is mostly true, Humira has a successful copay assistance program to lower prescription costs for consumers. According to a 2022 IQVIA report, 82% of commercial prescriptions cost patients less than $10 for Humira because of this program.
To appeal to patients, biosimilar companies will need to offer similar savings, Dr. Fendrick added. “There will be some discontent if patients are actually asked to pay more out-of-pocket for a less expensive drug,” he said.
All eight companies behind these biosimilars are offering or will be launching copay saving programs, many which advertise copays as low as $0 per month for eligible patients.
How will Humira respond?
Marta Wosińska, PhD, a health care economist at the Brookings Institute, Washington, predicts payers will use these lower biosimilar prices to negotiate better deals with AbbVie, Humira’s manufacturer. “We have a lot of players coming into [the market] right now, so the competition is really fierce,” she said. In response, AbbVie will need to increase rebates on Humira and/or lower its price to compete with these biosimilars.
“The ball is in AbbVie’s court,” she said. “If [the company] is not willing to drop price sufficiently, then payers will start switching to biosimilars.”
Dr. Fendrick reported past financial relationships and consulting arrangements with AbbVie, Amgen, Arnold Ventures, Bayer, CareFirst, BlueCross BlueShield, and many other companies. Dr. Wosińska has received funding from Arnold Ventures and serves as an expert witness on antitrust cases involving generic medication.
A version of this article first appeared on Medscape.com.
Verbal working memory deterioration predicts relapse in remitted psychosis
Previous research has suggested that cognitive impairments may predict recurrent psychotic episodes, but data on the association between specific cognitive deficits and relapse of psychosis over time are limited, wrote Tiffany J. Tao, MPhil, a PhD candidate at the University of Hong Kong, and colleagues.
In a naturalistic 1-year follow-up study published in Psychiatry Research , the researchers recruited psychosis patients with full remission for a least 6 months from two outpatient psychiatric clinics. The study population included adults aged 18-55 years, with an average age of 29.2 years; 62% were women. Relapse, defined as a recurrence of psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale, was assessed monthly via phone interviews with the use of a smartphone app. Cognitive decline was based on working memory deterioration, assessed monthly via the Visual Patterns Test (VPT) and the Letter-Number Sequencing (LNS) test, respectively, for visual and verbal working memory.
Overall, 18 patients (16%) experienced a relapse at 1 year. One-third of these (six patients) required hospitalization, with a median hospital stay of 23 days.
In a multivariate analysis, independent and significant predictors of relapse were verbal working memory deterioration 2 months prior to relapse (P = .029), worse medication adherence (P = .018), and less resilience (P = .014) with odds ratios of 9.445, 0.051, and 0.769, respectively.
“Specifically, declines in verbal working memory were observed beginning at 2 months prior to the relapse episode in both the univariate and multivariate models after controlling for other significant predictors,” the researchers wrote in their discussion.
The mechanism of action for the association remains unclear, but cognitive impairment might reflect dopamine dysregulation or other processes in the prefrontal cortex that could contribute to psychotic relapse, they said.
Other factors include the associations between cognitive impairment and medication nonadherence, and the impact of cognitive impairment on a patient’s ability to manage the stresses of daily living that could trigger a psychotic relapse, they added.
Notably, the current study identified verbal working memory, but not visual working memory, as a predictor of relapse, which is important given the different neurobiological bases for visual and verbal tasks, the researchers wrote.
The study findings were limited by several factors including the inability to identify weaker predictors of relapse given the low relapse rate, and potential lack of generalizability to other less homogeneous populations, and the exclusion of patients with illicit drug use, the researchers noted.
However, the results were strengthened by the prospective measurements that prevented recall bias, and the inclusion of other objective predictors of relapse. The findings highlight the potential for early intervention to prevent relapse based on cognitive assessment, which can be measured objectively in the clinical setting or remotely from home using digital technology, they concluded.
The study received no outside funding. Ms. Tao had no financial conflicts to disclose.
Previous research has suggested that cognitive impairments may predict recurrent psychotic episodes, but data on the association between specific cognitive deficits and relapse of psychosis over time are limited, wrote Tiffany J. Tao, MPhil, a PhD candidate at the University of Hong Kong, and colleagues.
In a naturalistic 1-year follow-up study published in Psychiatry Research , the researchers recruited psychosis patients with full remission for a least 6 months from two outpatient psychiatric clinics. The study population included adults aged 18-55 years, with an average age of 29.2 years; 62% were women. Relapse, defined as a recurrence of psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale, was assessed monthly via phone interviews with the use of a smartphone app. Cognitive decline was based on working memory deterioration, assessed monthly via the Visual Patterns Test (VPT) and the Letter-Number Sequencing (LNS) test, respectively, for visual and verbal working memory.
Overall, 18 patients (16%) experienced a relapse at 1 year. One-third of these (six patients) required hospitalization, with a median hospital stay of 23 days.
In a multivariate analysis, independent and significant predictors of relapse were verbal working memory deterioration 2 months prior to relapse (P = .029), worse medication adherence (P = .018), and less resilience (P = .014) with odds ratios of 9.445, 0.051, and 0.769, respectively.
“Specifically, declines in verbal working memory were observed beginning at 2 months prior to the relapse episode in both the univariate and multivariate models after controlling for other significant predictors,” the researchers wrote in their discussion.
The mechanism of action for the association remains unclear, but cognitive impairment might reflect dopamine dysregulation or other processes in the prefrontal cortex that could contribute to psychotic relapse, they said.
Other factors include the associations between cognitive impairment and medication nonadherence, and the impact of cognitive impairment on a patient’s ability to manage the stresses of daily living that could trigger a psychotic relapse, they added.
Notably, the current study identified verbal working memory, but not visual working memory, as a predictor of relapse, which is important given the different neurobiological bases for visual and verbal tasks, the researchers wrote.
The study findings were limited by several factors including the inability to identify weaker predictors of relapse given the low relapse rate, and potential lack of generalizability to other less homogeneous populations, and the exclusion of patients with illicit drug use, the researchers noted.
However, the results were strengthened by the prospective measurements that prevented recall bias, and the inclusion of other objective predictors of relapse. The findings highlight the potential for early intervention to prevent relapse based on cognitive assessment, which can be measured objectively in the clinical setting or remotely from home using digital technology, they concluded.
The study received no outside funding. Ms. Tao had no financial conflicts to disclose.
Previous research has suggested that cognitive impairments may predict recurrent psychotic episodes, but data on the association between specific cognitive deficits and relapse of psychosis over time are limited, wrote Tiffany J. Tao, MPhil, a PhD candidate at the University of Hong Kong, and colleagues.
In a naturalistic 1-year follow-up study published in Psychiatry Research , the researchers recruited psychosis patients with full remission for a least 6 months from two outpatient psychiatric clinics. The study population included adults aged 18-55 years, with an average age of 29.2 years; 62% were women. Relapse, defined as a recurrence of psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale, was assessed monthly via phone interviews with the use of a smartphone app. Cognitive decline was based on working memory deterioration, assessed monthly via the Visual Patterns Test (VPT) and the Letter-Number Sequencing (LNS) test, respectively, for visual and verbal working memory.
Overall, 18 patients (16%) experienced a relapse at 1 year. One-third of these (six patients) required hospitalization, with a median hospital stay of 23 days.
In a multivariate analysis, independent and significant predictors of relapse were verbal working memory deterioration 2 months prior to relapse (P = .029), worse medication adherence (P = .018), and less resilience (P = .014) with odds ratios of 9.445, 0.051, and 0.769, respectively.
“Specifically, declines in verbal working memory were observed beginning at 2 months prior to the relapse episode in both the univariate and multivariate models after controlling for other significant predictors,” the researchers wrote in their discussion.
The mechanism of action for the association remains unclear, but cognitive impairment might reflect dopamine dysregulation or other processes in the prefrontal cortex that could contribute to psychotic relapse, they said.
Other factors include the associations between cognitive impairment and medication nonadherence, and the impact of cognitive impairment on a patient’s ability to manage the stresses of daily living that could trigger a psychotic relapse, they added.
Notably, the current study identified verbal working memory, but not visual working memory, as a predictor of relapse, which is important given the different neurobiological bases for visual and verbal tasks, the researchers wrote.
The study findings were limited by several factors including the inability to identify weaker predictors of relapse given the low relapse rate, and potential lack of generalizability to other less homogeneous populations, and the exclusion of patients with illicit drug use, the researchers noted.
However, the results were strengthened by the prospective measurements that prevented recall bias, and the inclusion of other objective predictors of relapse. The findings highlight the potential for early intervention to prevent relapse based on cognitive assessment, which can be measured objectively in the clinical setting or remotely from home using digital technology, they concluded.
The study received no outside funding. Ms. Tao had no financial conflicts to disclose.
FROM PSYCHIATRY RESEARCH
Gut and oral flora linked to subclinical CAD, inflammation
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
TOPLINE:
in a population-based observational study.
METHODOLOGY:
Links between gut microbiota and coronary atherosclerosis have been studied primarily in symptomatic patients who were likely receiving therapies that may have shifted the balance of different organisms; there are fewer data from people with asymptomatic coronary disease.
Oral bacterial species are commonly transmitted to the gut, suggesting that gut and oral microbiota profiles are related and, further, that the gut may allow oral pathogenic bacteria to enter the circulation.
The current study included 8,973 adults (53.7% women) without cardiovascular (CV) disease for whom adequate imaging and other data were available from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) and the Malmö Offspring Study (MOS).
Researchers looked for associations between coronary artery calcium (CAC) scores (an index of atherosclerosis), gut bacterial species (identified in fecal samples), oral flora and pathologies, and systemic inflammatory biomarkers.
TAKEAWAY:
Among the 64 species that correlated with CAC scores independently of CV risk factors, 51 showed a positive association, especially S. anginosus and S. oralis subsp oralis; patients with higher levels of those two species generally had more CV risk factors.
Twenty-five bacterial species that correlated with CAC scores were also associated with any coronary plaque by CT angiography. Five such species were associated with coronary stenosis greater than 50%, 39 with the modified Duke index, and five with carotid plaques (P < .05).
Of 54 species positively associated with CAC scores, 13 also tracked with C-reactive protein levels by high-sensitivity assay, 10 with leukocyte counts, and 11 with neutrophil counts (P < .05).
Bacterial species common in the oral cavity made up most of the species that correlated with all three inflammatory biomarkers; they included the streptococci most strongly correlating with CAC scores, that is, S. anginosus, S. oralis subsp oralis, and S. parasanguinis.
IN PRACTICE:
If the associations between gut bacterial species and markers of coronary atherosclerosis are found to be causal, such bacteria may “contribute to atherogenesis by direct infection or by altering host metabolism,” the report states. “Future studies will show whether these species can be used as potential biomarkers or treatment targets.”
SOURCE:
The study was conducted by Sergi Sayols-Baixeras, PhD, Uppsala University, Sweden, and Instituto de Salud Carlos III, Madrid, and colleagues. It was published online July 12, 2023, in Circulation.
LIMITATIONS:
Few participants had a high degree of subclinical atherosclerosis, which may reduce statistical power. Fecal samples disclose organisms primarily from the distal colon, but “microbial composition can vary extensively throughout the gastrointestinal tract.” The investigators did not consider potential synergistic interactions among bacterial species that could influence their relationship to coronary atherosclerosis. Captured data regarding antibiotic therapy didn’t account for any in-hospital treatment. The study’s cross-sectional design precludes inferences about causation.
DISCLOSURES:
The study received funding from the European Research Council, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Foundation for Strategic Research, the G
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
25 years of Viagra: A huge change in attitudes about ED
This transcript has been edited for clarity.
Incredibly, 25 years ago, Bob Dole, a senator from Kansas at the time and former presidential candidate, went on national television in a commercial and discussed the fact that he was sexually impotent. You might be thinking, “What was happening then? Was this an early Jerry Springer experience or reality TV gone haywire?” No. Viagra was approved as a treatment 25 years ago this year.
Bob Dole was recruited by Pfizer, the manufacturer of Viagra, to do commercials in which he discussed his sexual dysfunction. He was recruited for a very specific set of reasons. First, he was a distinguished, prominent, respected national figure. Second, he was conservative.
For those of you who don’t remember, when 25 years ago Viagra first appeared, Pfizer was terrified that they would get attacked for promoting promiscuity by introducing a sex pill onto the market. Bob Dole was basically saying, “I have a medical problem. It’s tough to talk about, but there is a treatment. I’m going to discuss the fact that I, among many other men, could use this to help that problem.”
He was used in a way to deflect conservative or religious critics worried about the promotion of sex outside of marriage. Bob Dole was also well known to be married to Elizabeth Dole. This wasn’t somebody who was out on the dating market. Bob Dole was a family man, and his selection was no accident. For all these reasons, Bob Dole was the first spokesperson for Viagra.
Now, as it happens, I had a role to play with this drug. Pfizer called me up and asked me to come and do a consult with them about the ethics of this brand-new treatment. I had never been asked by a drug company to do anything like this. I didn’t know what I was doing. I thought about it and said: “I’ll do it if you let me sit in on discussions and meetings at your New York headquarters about this drug. I want open access.”
I assume they gave me open access. I went to many meetings before the Food and Drug Administration approved Viagra, and many discussions took place about how to roll it out. Once I got there, the one thing I insisted upon was that they had to be treating a disease. If they didn’t want to get involved in criticisms about this new miracle solution to the age-old problem of sexual dysfunction, impotence wouldn’t do. It wasn’t a medical diagnosis, and it was kind of a very undefined situation.
Erectile dysfunction was the answer. They met with urologists, sex experts, and individuals within the company and came up with the idea that if you were unable to have an erection after trying for 6 months or more, you suffered from erectile dysfunction, and that was the group for whom they should market Viagra. I fully agreed with that.
What happened was that probably hundreds of millions of men worldwide came forward for the first time and said, “I’m ashamed and guilty. I feel stigmatized. Now, with something that might help me, I’m going to say to my doctor, I have this problem.”
It’s a very important lesson because 25 years later, it’s still difficult for people – men and women – to discuss sexual problems, sexual dysfunction, and unhappiness with their sex life. I know we’ve gotten better at asking about this, but it’s still difficult for patients to go into it, bring it up, and talk about it. It’s something that we have to think hard about how we bring forward, honest, frank conversation and make people comfortable so they can tell us.
One thing that Viagra proved to the world is that not only is there a large amount of sexual dysfunction – some numbers as high as 35% of men over age 65 – but that sexual dysfunction is related to diseases. It’s caused by hypertension, hardening of the arteries, and diabetes. It may be caused by psychological anxiety or even just a poor relationship where things are falling apart.
I think it’s important that, when Viagra first appeared, what Pfizer tried to do and with the marketing oriented around it was treating it as a disease, trying to treat erectile dysfunction as a symptom, and then trying to explore the underlying possible causes for that symptom.
Sadly, if we look today, we have come a long way – and not always a good way – from where Viagra started. Viagra is easily available online. Many companies say, just get online and a doctor will talk with you about a prescription. They do, but they don’t explore the underlying causes anymore online of what might be causing the erectile dysfunction. They certainly may have a checkbox and ask somebody about this or that, but I’ve gone and tested the sites, and you can get a prescription in about 30 seconds.
It’s not really gone with the old medical model that accompanied the appearance of Viagra. We now treat it as a recreational drug or an aphrodisiac, none of which is true. If your body is working properly, blood will flow where it’s going to go. Taking Viagra or any of the other treatments will not help improve that or enhance that.
The other problem I see today with where we are with these impotence and erectile dysfunction drugs is that we still have not developed a full array of interventions for women. It’s true that men have Viagra, and it’s true that that’s often reimbursed. We still have women complaining that they have sexual dysfunction or loss of interest or whatever the problem might be, and we haven’t been able to develop drugs that will help them.
Since Viagra’s approval 25 years ago until the patent ran out in 2019, $40 billion worth of the drug has been sold. Its advertising has shifted so that
Doctors always need to be thinking about exploring that and trying to get a vision or a view of the health of their patients. It’s still hard for many people to speak up and say if they’re having problems in bed, and we want to make sure that we try our best to make that happen.
Overall, I think the approval of Viagra 25 years ago was a very good thing. It brought a terrible problem out into the open. It helped enhance the quality of life for many men. Despite where we are today, I think the introduction of that pill was actually a major achievement in pharmacology.
Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported conflicts of interest with Johnson & Johnson, Medscape, and Pfizer.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Incredibly, 25 years ago, Bob Dole, a senator from Kansas at the time and former presidential candidate, went on national television in a commercial and discussed the fact that he was sexually impotent. You might be thinking, “What was happening then? Was this an early Jerry Springer experience or reality TV gone haywire?” No. Viagra was approved as a treatment 25 years ago this year.
Bob Dole was recruited by Pfizer, the manufacturer of Viagra, to do commercials in which he discussed his sexual dysfunction. He was recruited for a very specific set of reasons. First, he was a distinguished, prominent, respected national figure. Second, he was conservative.
For those of you who don’t remember, when 25 years ago Viagra first appeared, Pfizer was terrified that they would get attacked for promoting promiscuity by introducing a sex pill onto the market. Bob Dole was basically saying, “I have a medical problem. It’s tough to talk about, but there is a treatment. I’m going to discuss the fact that I, among many other men, could use this to help that problem.”
He was used in a way to deflect conservative or religious critics worried about the promotion of sex outside of marriage. Bob Dole was also well known to be married to Elizabeth Dole. This wasn’t somebody who was out on the dating market. Bob Dole was a family man, and his selection was no accident. For all these reasons, Bob Dole was the first spokesperson for Viagra.
Now, as it happens, I had a role to play with this drug. Pfizer called me up and asked me to come and do a consult with them about the ethics of this brand-new treatment. I had never been asked by a drug company to do anything like this. I didn’t know what I was doing. I thought about it and said: “I’ll do it if you let me sit in on discussions and meetings at your New York headquarters about this drug. I want open access.”
I assume they gave me open access. I went to many meetings before the Food and Drug Administration approved Viagra, and many discussions took place about how to roll it out. Once I got there, the one thing I insisted upon was that they had to be treating a disease. If they didn’t want to get involved in criticisms about this new miracle solution to the age-old problem of sexual dysfunction, impotence wouldn’t do. It wasn’t a medical diagnosis, and it was kind of a very undefined situation.
Erectile dysfunction was the answer. They met with urologists, sex experts, and individuals within the company and came up with the idea that if you were unable to have an erection after trying for 6 months or more, you suffered from erectile dysfunction, and that was the group for whom they should market Viagra. I fully agreed with that.
What happened was that probably hundreds of millions of men worldwide came forward for the first time and said, “I’m ashamed and guilty. I feel stigmatized. Now, with something that might help me, I’m going to say to my doctor, I have this problem.”
It’s a very important lesson because 25 years later, it’s still difficult for people – men and women – to discuss sexual problems, sexual dysfunction, and unhappiness with their sex life. I know we’ve gotten better at asking about this, but it’s still difficult for patients to go into it, bring it up, and talk about it. It’s something that we have to think hard about how we bring forward, honest, frank conversation and make people comfortable so they can tell us.
One thing that Viagra proved to the world is that not only is there a large amount of sexual dysfunction – some numbers as high as 35% of men over age 65 – but that sexual dysfunction is related to diseases. It’s caused by hypertension, hardening of the arteries, and diabetes. It may be caused by psychological anxiety or even just a poor relationship where things are falling apart.
I think it’s important that, when Viagra first appeared, what Pfizer tried to do and with the marketing oriented around it was treating it as a disease, trying to treat erectile dysfunction as a symptom, and then trying to explore the underlying possible causes for that symptom.
Sadly, if we look today, we have come a long way – and not always a good way – from where Viagra started. Viagra is easily available online. Many companies say, just get online and a doctor will talk with you about a prescription. They do, but they don’t explore the underlying causes anymore online of what might be causing the erectile dysfunction. They certainly may have a checkbox and ask somebody about this or that, but I’ve gone and tested the sites, and you can get a prescription in about 30 seconds.
It’s not really gone with the old medical model that accompanied the appearance of Viagra. We now treat it as a recreational drug or an aphrodisiac, none of which is true. If your body is working properly, blood will flow where it’s going to go. Taking Viagra or any of the other treatments will not help improve that or enhance that.
The other problem I see today with where we are with these impotence and erectile dysfunction drugs is that we still have not developed a full array of interventions for women. It’s true that men have Viagra, and it’s true that that’s often reimbursed. We still have women complaining that they have sexual dysfunction or loss of interest or whatever the problem might be, and we haven’t been able to develop drugs that will help them.
Since Viagra’s approval 25 years ago until the patent ran out in 2019, $40 billion worth of the drug has been sold. Its advertising has shifted so that
Doctors always need to be thinking about exploring that and trying to get a vision or a view of the health of their patients. It’s still hard for many people to speak up and say if they’re having problems in bed, and we want to make sure that we try our best to make that happen.
Overall, I think the approval of Viagra 25 years ago was a very good thing. It brought a terrible problem out into the open. It helped enhance the quality of life for many men. Despite where we are today, I think the introduction of that pill was actually a major achievement in pharmacology.
Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported conflicts of interest with Johnson & Johnson, Medscape, and Pfizer.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Incredibly, 25 years ago, Bob Dole, a senator from Kansas at the time and former presidential candidate, went on national television in a commercial and discussed the fact that he was sexually impotent. You might be thinking, “What was happening then? Was this an early Jerry Springer experience or reality TV gone haywire?” No. Viagra was approved as a treatment 25 years ago this year.
Bob Dole was recruited by Pfizer, the manufacturer of Viagra, to do commercials in which he discussed his sexual dysfunction. He was recruited for a very specific set of reasons. First, he was a distinguished, prominent, respected national figure. Second, he was conservative.
For those of you who don’t remember, when 25 years ago Viagra first appeared, Pfizer was terrified that they would get attacked for promoting promiscuity by introducing a sex pill onto the market. Bob Dole was basically saying, “I have a medical problem. It’s tough to talk about, but there is a treatment. I’m going to discuss the fact that I, among many other men, could use this to help that problem.”
He was used in a way to deflect conservative or religious critics worried about the promotion of sex outside of marriage. Bob Dole was also well known to be married to Elizabeth Dole. This wasn’t somebody who was out on the dating market. Bob Dole was a family man, and his selection was no accident. For all these reasons, Bob Dole was the first spokesperson for Viagra.
Now, as it happens, I had a role to play with this drug. Pfizer called me up and asked me to come and do a consult with them about the ethics of this brand-new treatment. I had never been asked by a drug company to do anything like this. I didn’t know what I was doing. I thought about it and said: “I’ll do it if you let me sit in on discussions and meetings at your New York headquarters about this drug. I want open access.”
I assume they gave me open access. I went to many meetings before the Food and Drug Administration approved Viagra, and many discussions took place about how to roll it out. Once I got there, the one thing I insisted upon was that they had to be treating a disease. If they didn’t want to get involved in criticisms about this new miracle solution to the age-old problem of sexual dysfunction, impotence wouldn’t do. It wasn’t a medical diagnosis, and it was kind of a very undefined situation.
Erectile dysfunction was the answer. They met with urologists, sex experts, and individuals within the company and came up with the idea that if you were unable to have an erection after trying for 6 months or more, you suffered from erectile dysfunction, and that was the group for whom they should market Viagra. I fully agreed with that.
What happened was that probably hundreds of millions of men worldwide came forward for the first time and said, “I’m ashamed and guilty. I feel stigmatized. Now, with something that might help me, I’m going to say to my doctor, I have this problem.”
It’s a very important lesson because 25 years later, it’s still difficult for people – men and women – to discuss sexual problems, sexual dysfunction, and unhappiness with their sex life. I know we’ve gotten better at asking about this, but it’s still difficult for patients to go into it, bring it up, and talk about it. It’s something that we have to think hard about how we bring forward, honest, frank conversation and make people comfortable so they can tell us.
One thing that Viagra proved to the world is that not only is there a large amount of sexual dysfunction – some numbers as high as 35% of men over age 65 – but that sexual dysfunction is related to diseases. It’s caused by hypertension, hardening of the arteries, and diabetes. It may be caused by psychological anxiety or even just a poor relationship where things are falling apart.
I think it’s important that, when Viagra first appeared, what Pfizer tried to do and with the marketing oriented around it was treating it as a disease, trying to treat erectile dysfunction as a symptom, and then trying to explore the underlying possible causes for that symptom.
Sadly, if we look today, we have come a long way – and not always a good way – from where Viagra started. Viagra is easily available online. Many companies say, just get online and a doctor will talk with you about a prescription. They do, but they don’t explore the underlying causes anymore online of what might be causing the erectile dysfunction. They certainly may have a checkbox and ask somebody about this or that, but I’ve gone and tested the sites, and you can get a prescription in about 30 seconds.
It’s not really gone with the old medical model that accompanied the appearance of Viagra. We now treat it as a recreational drug or an aphrodisiac, none of which is true. If your body is working properly, blood will flow where it’s going to go. Taking Viagra or any of the other treatments will not help improve that or enhance that.
The other problem I see today with where we are with these impotence and erectile dysfunction drugs is that we still have not developed a full array of interventions for women. It’s true that men have Viagra, and it’s true that that’s often reimbursed. We still have women complaining that they have sexual dysfunction or loss of interest or whatever the problem might be, and we haven’t been able to develop drugs that will help them.
Since Viagra’s approval 25 years ago until the patent ran out in 2019, $40 billion worth of the drug has been sold. Its advertising has shifted so that
Doctors always need to be thinking about exploring that and trying to get a vision or a view of the health of their patients. It’s still hard for many people to speak up and say if they’re having problems in bed, and we want to make sure that we try our best to make that happen.
Overall, I think the approval of Viagra 25 years ago was a very good thing. It brought a terrible problem out into the open. It helped enhance the quality of life for many men. Despite where we are today, I think the introduction of that pill was actually a major achievement in pharmacology.
Dr. Kaplan is director, division of medical ethics, New York University Langone Medical Center, New York. He reported conflicts of interest with Johnson & Johnson, Medscape, and Pfizer.
A version of this article first appeared on Medscape.com.
A risk for adverse events in cancer meds cleared renally
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
Phenotypes drive antibiotic response in youth with bronchiectasis
Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.
Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.
Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.
In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.
Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.
In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).
Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).
The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.
Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.
Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.
Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.
The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.
However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.
The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.
Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.
Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.
In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.
Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.
In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).
Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).
The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.
Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.
Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.
Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.
The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.
However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.
The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.
Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.
Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.
In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.
Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.
In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).
Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).
The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.
Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.
Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.
Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.
The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.
However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.
The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
FROM THE JOURNAL CHEST
COPD: Large-scale study suggests protective role for vitamin D
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
COPD risk was 23% higher in people within the lowest quintile vs. the fourth quintile of 25(OH)D concentrations, according to research appearing in BMJ Open Respiratory Research.
While low vitamin D status has been linked to increased inflammatory diseases risk and to the regulation of pathogenic mechanisms in COPD, epidemiological evidence regarding the associations of 25(OH)D concentrations with COPD incidence and survival remains inconclusive, Zheng Zhu, MD, of Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, and colleagues wrote.
From UK Biobank data recorded from 403,648 participants (mean age 56.4 years; 54% women) who were free of COPD at baseline and had 25(OH)D measurements, researchers estimated hazard ratios and 95% confidence intervals for the associations of 25(OH)D concentrations with COPD risk and survival. After median follow-up of 12.3 years (ending Sept. 30, 2021), with 11,008 COPD cases recorded, beyond the COPD and mortality increase (HR, 1.23; 95% CI, 1.16-1.31) in the lowest quintile of 25(OH)D concentrations, risk for overall death was 38% higher, as well (HR, 1.38; 95% CI, 1.22-1.56). Serum concentrations were greater than 64.6 nmol/L in the highest (quintile 5) and less than 31.7 nmol/L in the lowest (quintile 1). Also, men and current smokers had higher COPD and mortality risk (P interaction for both: < .05).
While event rates tracked generally inversely with 25(OH)D concentrations, overall the event curves were non-linear. Dr Zhu and associates reported that the decreasing risk of COPD appeared to be lowest at 55 nmol/L of 25(OH)D within quintile 4 (51.8 to < 64.6 nmol/L). Furthermore, lower prediagnostic 25(OH)D concentrations were associated with a significant decrease in overall and COPD-specific survival.
Smoking is the most commonly encountered risk factor for COPD, the researchers noted, and their findings indicated that 25(OH)D concentrations were inversely associated with COPD risk in both smokers and never-smokers. In a fully adjusted model, compared with quintile 4, the quintile 1 increase in COPD risk was 25% in never-smokers and 23% in smokers.
“Our findings imply that vitamin D might play a role in progression of COPD,” the authors stated. They added, “Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale RCTs.”
“Vitamin D has an important function in the immune system and lower serum levels have been implicated in a variety of inflammatory diseases,” commented associate professor of medicine Diego J. Maselli, MD, who is chief of the division of pulmonary diseases & critical care at UT Health San Antonio. “Patients with COPD often have lower levels of vitamin D compared to healthy individuals. COPD patients with low serum levels of vitamin D may have a higher risk of exacerbations and worse lung function.”
He added, “The research by Zhu and colleagues adds to the field of study and highlights the potential role of vitamin D in the pathophysiology of COPD. It is important to remember that these associations do not establish causality, as patients with chronic and debilitating diseases may have limited sunlight exposure, poor nutritional intake, and other behaviors that may affect vitamin D levels. There are mixed results in studies evaluating the role of supplementing vitamin D in COPD with regards to disease progression and exacerbation reduction. While there are some studies that report that supplementation of vitamin D can reduce COPD exacerbations, there is still a need for randomized controlled studies that explore if the supplementation of vitamin D can prevent the development of COPD, particularly in those who actively smoke. Yet, it is reasonable to evaluate the serum vitamin D levels in COPD patients who have had exacerbations and supplement when there is a severe deficiency.”
Given that the majority of participants in this study were from the United Kingdom, the researchers stated, a study limitation is that findings might not apply to other populations.
No disclosures were reported by Dr. Zhu or by Dr. Maselli.
FROM BMJ OPEN RESPIRATORY RESEARCH
Retinal thickness a new predictor of MS disability?
The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.
The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.
This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.
Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.
Retinal layers of interest
OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”
However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.
To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.
Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.
Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.
Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.
At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
Independent predictors of disability
To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.
After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.
Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).
Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”
For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.
Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
Strengths, limitations
Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).
Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.
Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.
This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.
“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.
The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.
In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.
However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.
“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
Important research
Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”
However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.
Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.
Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.
“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”
Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”
Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”
Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.
Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.
This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.
Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.
A version of this article appeared on Medscape.com.
The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.
The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.
This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.
Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.
Retinal layers of interest
OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”
However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.
To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.
Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.
Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.
Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.
At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
Independent predictors of disability
To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.
After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.
Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).
Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”
For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.
Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
Strengths, limitations
Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).
Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.
Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.
This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.
“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.
The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.
In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.
However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.
“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
Important research
Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”
However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.
Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.
Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.
“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”
Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”
Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”
Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.
Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.
This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.
Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.
A version of this article appeared on Medscape.com.
The researchers measured retinal thickness using optical coherence tomography (OCT) within 3 months of diagnosis for more than 230 patients with MS and found that thinning of the retina was associated with a more than fourfold increased risk of Expanded Disability Status Scale (EDSS) scores of at least 3.0.
The OCT “basically tells you how much nerve layer is left in the glass,” said study investigator Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna.
This “could potentially inform treatment strategies, but that is another direction which will be investigated hopefully in the near future,” he added. However, the imaging technique cannot be used for all patients and is currently not widely available.
Dr. Bsteh presented the results at the annual meeting of the European Academy of Neurology.
Retinal layers of interest
OCT produces images of the retina and measures its thickness, Dr. Bsteh explained. Of greatest interest and relevance to patients with MS are two layers – the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL), which are associated with “future physical and cognitive disability and brain atrophy, and are reliable biomarkers of axonal damage.”
However, he said, what is not yet known is whether the baseline thickness of these two layers independently predicts progression of disability in patients with newly diagnosed disease within the framework of all of the other known risk factors.
To investigate, the team used data from ViennOCTiMS, an ongoing prospective observational cohort study conducted in Vienna and Innsbruck. For the analysis, they included patients newly diagnosed with relapsing MS using the 2017 McDonald criteria.
Study participants were required to undergo a spectral-domain OCT scan within 90 days of diagnosis and within 270 days of symptom onset. They also had to undergo follow-up of at least 12 months.
Among 231 patients included in the study, 74 were female, and the mean age was 30.3 years.
Dr. Bsteh noted that disease duration was short. There was a median of 45 days between initial diagnosis and the OCT scan. The median number of T2 lesions on MRI was 11, with 59.3% of patients had at least 10 lesions.
At baseline, 13.0% of patients were not receiving drug therapy, although they were advised to do so, said Dr. Bsteh. A total of 59.7% of patients received “moderately effective” disease-modifying treatments, while 27.3% were treated with “highly effective” DMTs.
Independent predictors of disability
To determine the contribution of retinal thickness to the risk of developing EDSS of 3.0 or more, the researchers conducted a multivariate analysis that accounted for patient age and sex, the type of first relapse, the remission of first relapse symptoms, the presence of oligoclonal bands, the baseline number of T2 lesions, and the use and type of DMT.
After approximately 96 months of follow-up, a pRNFL thickness of 88 mcm or less at baseline was associated with a hazard ratio for EDSS of at least 3.0 versus a thickness of greater than 88 mcm of 4.0 (P < .001), Dr. Bsteh reported.
Similarly, a GCL thickness of less than 77 mcm at baseline was associated with a HR for EDSS of at least 3.0 of 5.1 (P < .001).
Subgroup analysis indicated that both measures of retinal thickness were indeed independent predictors of EDSS. Dr. Bsteh said: “It was encouraging to see that all the unknown prognostic factor factors performed within the expected framework.”
For example, there was a notable association between the risk of EDSS of at least 3.0 and patient age, as well as with incomplete remission and a greater number of lesions on MRI.
Dr. Bsteh said it was also “very encouraging” to find that high-efficacy DMT was associated with a reduced risk of EDSS of at least 3.0.
Strengths, limitations
Turning to the relatively recently described progression independent of relapse activity, Dr. Bsteh showed that both pRNFL of 88 mcm or less and GCL less than 77 mcm were significantly associated with the development of PIRA, compared with greater thickness, at HRs of 3.1 and 4.1, respectively (P < .001 for both).
Subgroup analysis again supported the independent contribution of retinal thickness to the risk of PIRA and revealed similar associations with known risk factors, although the contribution of highly effective DMT was of borderline significance for this outcome.
Interestingly, neither pRNFL of 88 mcm or less nor GCL less than 77 mcm was significantly associated with the time to second clinical attack, “which is basically the correlation of the inflammatory activity” in MS, said Dr. Bsteh.
This, he continued, “goes back to the basic theory that EDSS, PIRA, and neurodegenerative problems are associated with the OCT but not the degree of inflammatory activity.
“As good as all that sounds, there are of course, some limitations” to the study, Dr. Bsteh acknowledged.
The most important limitation is that the changes measured on OCT were “not specific to multiple sclerosis,” and the thickness of the layers “can be influenced by a lot of other factors,” in particular by eye conditions such as glaucoma and diabetes mellitus.
In addition, OCT is not reliable for patients with myopia of more than four to six diopters and for those with retinal comorbidities, such as optic drusen. Dr. Bsteh also pointed out that automatic segmentation in OCT requires stringent quality control.
However, the “biggest problem for the deployment of OCT in the clinical routine is its lack of availability. It’s not very easy for neurologists to procure an OCT,” said Dr. Bsteh.
“You can always create it with your ophthalmologist of trust, but you have to know what you’re looking for,” he added.
Important research
Commenting on the study, Giancarlo Comi, MD, honorary professor of neurology at the Università Vita Salute San Raffaele and founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele, both in Milan, characterized the research as “very, very important and interesting.”
However, he said that he was a “bit surprised” that it showed no association between OCT measures and the second clinical attack, noting that longitudinal research by his team found such an association.
Dr. Comi added that the “key point” from the current study is that there was no such association in the early phase of the disease, which suggests that the amount of inflammatory activity “is not so relevant” in determining the degree of damage seen on OCT at that point.
Dr. Bsteh said he partially agreed with Dr. Comi, adding that “it depends on what you adjust for.
“If we did the same analysis without adjusting for the number of MRI lesions, we would see an association with second clinical attack,” he said. However, the aim of the current study was to determine the independent contribution of retinal thickness, “and that’s why we tried to adjust to everything which was available to us.”
Dr. Bsteh also underlined that it was a cross-sectional analysis conducted “very, very early” in the MS disease course, and “so the inflammatory activity did not yet have a chance to influence the thickness on the OCT.”
Had OCT been performed later in the disease course, inflammatory activity might have influenced the findings, but the intention of the study was to use it “as an early marker to try to stratify patients who are at risk, and [those] who are maybe a little less at risk, and inform the treatment strategy.”
Maria Assunta Rocca, MD, associate professor of neurology at Università Vita Salute San Raffaele, and head of neuroimaging of the CNS white matter unit at IRCCS San Raffaele Scientific Institute, Milan, who cochaired the session in which the study was presented, asked whether the researchers analyzed patients with optic neuritis separately from those without and whether it affected the predictive factors.
Dr. Bsteh said that OCT cannot be used for patients with bilateral optic neuritis and so they were excluded from the study, but for patients who were affected unilaterally, the contralateral eye was assessed.
This underlines why OCT contributes the most when used early on the disease course. “The longer the disease has time, the higher the likelihood that optic neuritis has developed,” he said.
Funding for the study was provided by Mindset Technologies. All authors are, or were, employees and/or shareholders of Mindset Technologies. Dr. Bsteh has relationships with Biogen, Celgene/Bristol-Myers Squibb, Lilly, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.
A version of this article appeared on Medscape.com.
FROM EAN 2023
Opioid initiation in dementia tied to an 11-fold increased risk of death
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
From AAIC 2023