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‘Bane of my existence:’ The burden of Medicare Advantage denials
, a recent analysis suggests.
The report from the Office of Inspector General (OIG) of the U.S. Department of Health & Human Services found that 13% of prior authorization denials were for service requests, which included cancer care, that met Medicare coverage rules and 18% of payment denials were for claims that met Medicare coverage and MAO billing rules, delaying or halting payments for services that clinicians had provided.
MAO denials are the “bane of my existence,” said Michael Buckstein, MD, PhD, a radiation oncologist at Mount Sinai Hospital in New York.
“Working at a large hospital in a metropolitan city, we spend enormous and increasing amounts of time on prior approvals and we get denials quite frequently, which certainly can lead to delays in treatment,” said Dr. Buckstein, who reviewed the OIG report for this news organization.
According to Dr. Buckstein, once a claim is denied, staff must spend time filing and scheduling an appeal, and if the appeal is denied in a physician peer-to-peer review, staff could face secondary and tertiary appeals. “We have been living with this frustration for a long time,” Dr. Buckstein said.
Widespread and persistent problems
Medicare Advantage plans, which are approved by the Centers for Medicare & Medicaid Services but run by private companies, continue to grow in popularity.
In 2021, 26.4 million Medicare beneficiaries (42%) were enrolled in a Medicare Advantage plan, and by 2030, about 51% of all Medicare beneficiaries will be enrolled, according to estimates from the Kaiser Family Foundation.
“Although MAOs approve the vast majority of prior authorization requests and provider payment requests, MAOs also deny millions of requests each year,” the OIG wrote. “CMS’s annual audits of MAOs have highlighted widespread and persistent problems related to inappropriate denials of services and payment.”
In the current report, the OIG reviewed case files for 247 denials of prior authorization requests and 183 payment denials issued by 15 of the largest MAOs during 1 week in June of 2019.
The authors found that 13% of prior authorization denials occurred for service requests that met Medicare coverage rules, meaning these services would likely have been approved had the patient been enrolled in traditional Medicare.
The most prominent service types among these denials included imaging services, stays in postacute facilities, and injections.
In one case, for example, the MAO stated that a beneficiary would need to wait at least 1 year for a follow-up MRI because the size of the patient’s adrenal lesion (< 2 cm) was too small to warrant follow-up before 1 year. However, this restriction is not included in Medicare coverage rules. And an OIG physician panel found that the documentation in the original request demonstrated that the MRI was medically necessary to determine whether the lesion seen on an earlier CT scan was malignant.
Upon appeal, the MAO reversed its original denial.
Among the payment requests that MAOs denied, almost one in five were for claims that met Medicare coverage and billing rules, which delayed or prevented payments for services already delivered. Most payment denials were caused by human error during manual claims-processing reviews and system processing errors, the OIG report found.
In one case, for example, a MAO denied payment for radiation treatment for a patient with a tumor on the pancreas, incorrectly claiming that no prior authorization had been submitted for the service. However, the physician subsequently provided a screenshot demonstrating that the MAO had granted prior authorization for the billed claim, and the MAO reversed the denial.
Most of these prior authorization denial reversals occurred because of an appeal filed by the beneficiary or the provider, which can take weeks.
In one case, an MAO denied a request for a CT scan of the chest and pelvis for a beneficiary with endometrial cancer. It took 5 weeks for the provider to get the denial reversed. The OIG panel determined that the original request included sufficient documentation to demonstrate the CT was needed to assess the stage of the cancer and determine the appropriate course of treatment.
These denials and reversals not only waste time but may also cause harm. In a 2021 American Medical Association survey, 34% of physicians reported that prior authorization led to a serious adverse event for a patient in their care, including hospitalization, medical intervention to prevent permanent impairment, and even disability or death.
Almost 90% of the physicians surveyed described the burden associated with prior authorizations as ‘high’ or ‘extremely high.’ More specifically, physicians and their staff spend nearly 2 days a week on prior authorizations and 40% of physicians have staff who work exclusively on prior authorizations.
“It’s just not the way medicine should be practiced, especially for cancer patients who are very vulnerable and want rapid care,” Dr. Buckstein said.
Time for action
Weighing in on the OIG report, Robert E. Wailes, MD, president of the California Medical Association, noted that “it has become common practice for health insurance companies to create obstacles for patients in hopes of not having to pay for essential healthcare.”
The reason for these obstacles is simple, he said: “Fewer procedures performed translates to larger insurance company profits.”
America’s Health Insurance Plans (AHIP) defended prior authorization, saying it is “an important patient safety, cost-saving, and waste-prevention tool.”
The group also called out the OIG review for its “extraordinarily small” sample of 247 prior authorization requests over 1 week.
“Drawing far-reaching conclusions based on a very small sample of data and misleading headlines is not a productive way to improve our healthcare system for patients,” the AHIP statement reads.
But, according to Anna Schwamlein Howard, who works on policy development at the American Cancer Society Cancer Action Network, the recent OIG report is in line with previous OIG reports.
And, Ms. Howard emphasized, the current report and others like it “highlight the need for CMS to utilize its audit authority and ensure that beneficiaries have access to medically necessary treatments, particularly cancer treatments.”
Along those lines, the OIG report recommends that the CMS should issue new guidance on the appropriate use of MAO clinical criteria in medical necessity reviews, update its audit protocols to address issues identified in the report, and direct MAOs to take additional steps to identify and address vulnerabilities that can lead to manual review and system errors.
In a statement, the CMS said it is committed to oversight and enforcement of the requirements of the Medicare Advantage program and agreed with the OIG recommendations.
“Lawmakers must act now to place patient needs before corporate profits and simplify by streamlining prior authorization processes,” Dr. Wailes said.
The ACS recently released a paper on this topic entitled, “The Medicare Appeals Process: Reforms Needed to Ensure Beneficiary Access.”
A version of this article first appeared on Medscape.com.
, a recent analysis suggests.
The report from the Office of Inspector General (OIG) of the U.S. Department of Health & Human Services found that 13% of prior authorization denials were for service requests, which included cancer care, that met Medicare coverage rules and 18% of payment denials were for claims that met Medicare coverage and MAO billing rules, delaying or halting payments for services that clinicians had provided.
MAO denials are the “bane of my existence,” said Michael Buckstein, MD, PhD, a radiation oncologist at Mount Sinai Hospital in New York.
“Working at a large hospital in a metropolitan city, we spend enormous and increasing amounts of time on prior approvals and we get denials quite frequently, which certainly can lead to delays in treatment,” said Dr. Buckstein, who reviewed the OIG report for this news organization.
According to Dr. Buckstein, once a claim is denied, staff must spend time filing and scheduling an appeal, and if the appeal is denied in a physician peer-to-peer review, staff could face secondary and tertiary appeals. “We have been living with this frustration for a long time,” Dr. Buckstein said.
Widespread and persistent problems
Medicare Advantage plans, which are approved by the Centers for Medicare & Medicaid Services but run by private companies, continue to grow in popularity.
In 2021, 26.4 million Medicare beneficiaries (42%) were enrolled in a Medicare Advantage plan, and by 2030, about 51% of all Medicare beneficiaries will be enrolled, according to estimates from the Kaiser Family Foundation.
“Although MAOs approve the vast majority of prior authorization requests and provider payment requests, MAOs also deny millions of requests each year,” the OIG wrote. “CMS’s annual audits of MAOs have highlighted widespread and persistent problems related to inappropriate denials of services and payment.”
In the current report, the OIG reviewed case files for 247 denials of prior authorization requests and 183 payment denials issued by 15 of the largest MAOs during 1 week in June of 2019.
The authors found that 13% of prior authorization denials occurred for service requests that met Medicare coverage rules, meaning these services would likely have been approved had the patient been enrolled in traditional Medicare.
The most prominent service types among these denials included imaging services, stays in postacute facilities, and injections.
In one case, for example, the MAO stated that a beneficiary would need to wait at least 1 year for a follow-up MRI because the size of the patient’s adrenal lesion (< 2 cm) was too small to warrant follow-up before 1 year. However, this restriction is not included in Medicare coverage rules. And an OIG physician panel found that the documentation in the original request demonstrated that the MRI was medically necessary to determine whether the lesion seen on an earlier CT scan was malignant.
Upon appeal, the MAO reversed its original denial.
Among the payment requests that MAOs denied, almost one in five were for claims that met Medicare coverage and billing rules, which delayed or prevented payments for services already delivered. Most payment denials were caused by human error during manual claims-processing reviews and system processing errors, the OIG report found.
In one case, for example, a MAO denied payment for radiation treatment for a patient with a tumor on the pancreas, incorrectly claiming that no prior authorization had been submitted for the service. However, the physician subsequently provided a screenshot demonstrating that the MAO had granted prior authorization for the billed claim, and the MAO reversed the denial.
Most of these prior authorization denial reversals occurred because of an appeal filed by the beneficiary or the provider, which can take weeks.
In one case, an MAO denied a request for a CT scan of the chest and pelvis for a beneficiary with endometrial cancer. It took 5 weeks for the provider to get the denial reversed. The OIG panel determined that the original request included sufficient documentation to demonstrate the CT was needed to assess the stage of the cancer and determine the appropriate course of treatment.
These denials and reversals not only waste time but may also cause harm. In a 2021 American Medical Association survey, 34% of physicians reported that prior authorization led to a serious adverse event for a patient in their care, including hospitalization, medical intervention to prevent permanent impairment, and even disability or death.
Almost 90% of the physicians surveyed described the burden associated with prior authorizations as ‘high’ or ‘extremely high.’ More specifically, physicians and their staff spend nearly 2 days a week on prior authorizations and 40% of physicians have staff who work exclusively on prior authorizations.
“It’s just not the way medicine should be practiced, especially for cancer patients who are very vulnerable and want rapid care,” Dr. Buckstein said.
Time for action
Weighing in on the OIG report, Robert E. Wailes, MD, president of the California Medical Association, noted that “it has become common practice for health insurance companies to create obstacles for patients in hopes of not having to pay for essential healthcare.”
The reason for these obstacles is simple, he said: “Fewer procedures performed translates to larger insurance company profits.”
America’s Health Insurance Plans (AHIP) defended prior authorization, saying it is “an important patient safety, cost-saving, and waste-prevention tool.”
The group also called out the OIG review for its “extraordinarily small” sample of 247 prior authorization requests over 1 week.
“Drawing far-reaching conclusions based on a very small sample of data and misleading headlines is not a productive way to improve our healthcare system for patients,” the AHIP statement reads.
But, according to Anna Schwamlein Howard, who works on policy development at the American Cancer Society Cancer Action Network, the recent OIG report is in line with previous OIG reports.
And, Ms. Howard emphasized, the current report and others like it “highlight the need for CMS to utilize its audit authority and ensure that beneficiaries have access to medically necessary treatments, particularly cancer treatments.”
Along those lines, the OIG report recommends that the CMS should issue new guidance on the appropriate use of MAO clinical criteria in medical necessity reviews, update its audit protocols to address issues identified in the report, and direct MAOs to take additional steps to identify and address vulnerabilities that can lead to manual review and system errors.
In a statement, the CMS said it is committed to oversight and enforcement of the requirements of the Medicare Advantage program and agreed with the OIG recommendations.
“Lawmakers must act now to place patient needs before corporate profits and simplify by streamlining prior authorization processes,” Dr. Wailes said.
The ACS recently released a paper on this topic entitled, “The Medicare Appeals Process: Reforms Needed to Ensure Beneficiary Access.”
A version of this article first appeared on Medscape.com.
, a recent analysis suggests.
The report from the Office of Inspector General (OIG) of the U.S. Department of Health & Human Services found that 13% of prior authorization denials were for service requests, which included cancer care, that met Medicare coverage rules and 18% of payment denials were for claims that met Medicare coverage and MAO billing rules, delaying or halting payments for services that clinicians had provided.
MAO denials are the “bane of my existence,” said Michael Buckstein, MD, PhD, a radiation oncologist at Mount Sinai Hospital in New York.
“Working at a large hospital in a metropolitan city, we spend enormous and increasing amounts of time on prior approvals and we get denials quite frequently, which certainly can lead to delays in treatment,” said Dr. Buckstein, who reviewed the OIG report for this news organization.
According to Dr. Buckstein, once a claim is denied, staff must spend time filing and scheduling an appeal, and if the appeal is denied in a physician peer-to-peer review, staff could face secondary and tertiary appeals. “We have been living with this frustration for a long time,” Dr. Buckstein said.
Widespread and persistent problems
Medicare Advantage plans, which are approved by the Centers for Medicare & Medicaid Services but run by private companies, continue to grow in popularity.
In 2021, 26.4 million Medicare beneficiaries (42%) were enrolled in a Medicare Advantage plan, and by 2030, about 51% of all Medicare beneficiaries will be enrolled, according to estimates from the Kaiser Family Foundation.
“Although MAOs approve the vast majority of prior authorization requests and provider payment requests, MAOs also deny millions of requests each year,” the OIG wrote. “CMS’s annual audits of MAOs have highlighted widespread and persistent problems related to inappropriate denials of services and payment.”
In the current report, the OIG reviewed case files for 247 denials of prior authorization requests and 183 payment denials issued by 15 of the largest MAOs during 1 week in June of 2019.
The authors found that 13% of prior authorization denials occurred for service requests that met Medicare coverage rules, meaning these services would likely have been approved had the patient been enrolled in traditional Medicare.
The most prominent service types among these denials included imaging services, stays in postacute facilities, and injections.
In one case, for example, the MAO stated that a beneficiary would need to wait at least 1 year for a follow-up MRI because the size of the patient’s adrenal lesion (< 2 cm) was too small to warrant follow-up before 1 year. However, this restriction is not included in Medicare coverage rules. And an OIG physician panel found that the documentation in the original request demonstrated that the MRI was medically necessary to determine whether the lesion seen on an earlier CT scan was malignant.
Upon appeal, the MAO reversed its original denial.
Among the payment requests that MAOs denied, almost one in five were for claims that met Medicare coverage and billing rules, which delayed or prevented payments for services already delivered. Most payment denials were caused by human error during manual claims-processing reviews and system processing errors, the OIG report found.
In one case, for example, a MAO denied payment for radiation treatment for a patient with a tumor on the pancreas, incorrectly claiming that no prior authorization had been submitted for the service. However, the physician subsequently provided a screenshot demonstrating that the MAO had granted prior authorization for the billed claim, and the MAO reversed the denial.
Most of these prior authorization denial reversals occurred because of an appeal filed by the beneficiary or the provider, which can take weeks.
In one case, an MAO denied a request for a CT scan of the chest and pelvis for a beneficiary with endometrial cancer. It took 5 weeks for the provider to get the denial reversed. The OIG panel determined that the original request included sufficient documentation to demonstrate the CT was needed to assess the stage of the cancer and determine the appropriate course of treatment.
These denials and reversals not only waste time but may also cause harm. In a 2021 American Medical Association survey, 34% of physicians reported that prior authorization led to a serious adverse event for a patient in their care, including hospitalization, medical intervention to prevent permanent impairment, and even disability or death.
Almost 90% of the physicians surveyed described the burden associated with prior authorizations as ‘high’ or ‘extremely high.’ More specifically, physicians and their staff spend nearly 2 days a week on prior authorizations and 40% of physicians have staff who work exclusively on prior authorizations.
“It’s just not the way medicine should be practiced, especially for cancer patients who are very vulnerable and want rapid care,” Dr. Buckstein said.
Time for action
Weighing in on the OIG report, Robert E. Wailes, MD, president of the California Medical Association, noted that “it has become common practice for health insurance companies to create obstacles for patients in hopes of not having to pay for essential healthcare.”
The reason for these obstacles is simple, he said: “Fewer procedures performed translates to larger insurance company profits.”
America’s Health Insurance Plans (AHIP) defended prior authorization, saying it is “an important patient safety, cost-saving, and waste-prevention tool.”
The group also called out the OIG review for its “extraordinarily small” sample of 247 prior authorization requests over 1 week.
“Drawing far-reaching conclusions based on a very small sample of data and misleading headlines is not a productive way to improve our healthcare system for patients,” the AHIP statement reads.
But, according to Anna Schwamlein Howard, who works on policy development at the American Cancer Society Cancer Action Network, the recent OIG report is in line with previous OIG reports.
And, Ms. Howard emphasized, the current report and others like it “highlight the need for CMS to utilize its audit authority and ensure that beneficiaries have access to medically necessary treatments, particularly cancer treatments.”
Along those lines, the OIG report recommends that the CMS should issue new guidance on the appropriate use of MAO clinical criteria in medical necessity reviews, update its audit protocols to address issues identified in the report, and direct MAOs to take additional steps to identify and address vulnerabilities that can lead to manual review and system errors.
In a statement, the CMS said it is committed to oversight and enforcement of the requirements of the Medicare Advantage program and agreed with the OIG recommendations.
“Lawmakers must act now to place patient needs before corporate profits and simplify by streamlining prior authorization processes,” Dr. Wailes said.
The ACS recently released a paper on this topic entitled, “The Medicare Appeals Process: Reforms Needed to Ensure Beneficiary Access.”
A version of this article first appeared on Medscape.com.
COVID booster mounts ‘brisk’ response in patients with cancer
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
FDA approves two vonoprazan therapies for H. pylori eradication
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
Vonoprazan is an oral potassium-competitive acid blocker and “the first innovative acid suppressant from a new drug class approved in the United States in over 30 years,” the company said in a news release announcing the approval.
“The approval of Voquezna treatment regimens offers physicians and patients two therapeutic options that showed superior eradication rates compared to proton pump inhibitor-based (PPI) lansoprazole triple therapy in the overall patient population in a pivotal trial,” Terrie Curran, president and CEO of Phathom Pharmaceuticals, said in the release.
“H. pylori eradication rates continue to decline in part due to antibiotic resistance, inadequate acid suppression, and complex treatment regimens, resulting in treatment failures and complications for patients,” Ms. Curran noted.
“New therapies that have the potential to address the limitations of current treatments are needed, and we look forward to bringing these innovative vonoprazan-based treatment options to the millions of H pylori sufferers in the United States,” Ms. Curran said.
FDA approval of vonoprazan triple and dual therapy was based on safety and efficacy data from the phase 3 PHALCON-HP trial involving 1,046 patients.
As earlier reported, both treatment regimens were noninferior to PPI-based triple therapy (lansoprazole with amoxicillin and clarithromycin) in patients with H. pylori strains that were not resistant to clarithromycin or amoxicillin at baseline.
In this analysis, the eradication rate was 78.8% with PPI-based triple therapy, compared with 84.7% with vonoprazan triple therapy and 78.5% with vonoprazan dual therapy.
Vonoprazan triple and dual therapy were both superior to PPI-based triple therapy among all patients, including patients with clarithromycin-resistant H. pylori.
Among patients with clarithromycin-resistant H. pylori, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% with vonoprazan triple therapy and 69.6% with vonoprazan dual therapy.
Among all patients, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy and 77.2% with vonoprazan dual therapy.
Adverse event rates for the vonoprazan-based regimens were comparable to lansoprazole triple therapy. Full prescribing information is available online.
“As a practicing physician, I am excited about the potential of two novel, first-line H. pylori treatment options,” William D. Chey, MD, chief of gastroenterology & hepatology at the University of Michigan, Ann Arbor, said in the news release.
“I believe the added flexibility of having two additional effective therapies, including a dual therapy option that does not contain clarithromycin, offers the potential to improve clinical outcomes in patients with H. pylori infection,” Dr. Chey added.
The company expects to launch both products in the third quarter of 2022. Both treatment regimens will be supplied in convenient blister packs to help promote compliance.
A version of this article first appeared on Medscape.com.
Best antioxidants to prevent age-related dementia identified?
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Depression biomarkers: Which ones matter most?
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
‘Forever chemicals’ linked to liver damage
(NAFLD), say the authors of a comprehensive evidence review.
They found “consistent” evidence for PFAS hepatotoxicity from rodent studies. In addition, exposure to PFAS was found to be associated with markers of liver function in observational studies in people.
The review, published online in Environmental Health Perspectives, may be the first systematic analysis of PFAS exposure and liver damage.
Possible contributor to growing NAFLD epidemic
In their analysis, the authors included 85 rodent studies and 24 epidemiologic studies, primarily involving people from the United States and largely focusing on four “legacy” PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS).
Meta-analyses of human studies found that higher levels of alanine aminotransferase were significantly associated with exposure to three of the older chemicals – PFOA, PFOS, and PFNA.
The “positive” and “convincing” associations between exposure to these synthetic chemicals and higher ALT levels suggest that exposure may contribute to the growing NAFLD epidemic, the researchers write.
Exposure to one of the chemicals, PFOA, was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in people.
In rodents, exposure to these synthetic chemicals consistently resulted in higher ALT levels and steatosis.
“The mechanism is not well understood yet, but there are a few proposed theories,” first author Elizabeth Costello, MPH, PhD student, department of population and public health sciences, University of Southern California, Los Angeles, told this news organization.
“PFAS are similar to fatty acids in chemical structure, so it’s possible that they activate some of the same receptors or otherwise interfere with fat metabolism. This might lead to inflammation or fat accumulation in the liver,” Ms. Costello explained.
People widely exposed
PFAS are ubiquitous in the environment. They have been detected in the blood of most people and have been linked to a variety of health concerns. Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
“We are exposed to PFAS in so many ways – through water, food, and products we use. It can be very difficult for individuals to control their own exposure,” Ms. Costello commented.
“At this point, it’s important to look for ways to remove PFAS from the environment and phase them out of our products and carefully consider the safety of any replacement chemicals,” she said.
Although most of the research to date has been limited to the four older PFAS (PFOA, PFOS, PFNA, and PFHxS), there are thousands of different PFAS chemicals.
“We don’t know very much about the effects of exposure to multiple PFAS at the same time or how newer replacement PFAS might affect liver disease or other health conditions,” Ms. Costello said.
Reached for comment, Lisa B. VanWagner, MD, with Northwestern University, Chicago, said this analysis is “very interesting,” but she is also “left wondering how we could do anything since it seems from my reading that these chemicals are ubiquitous and used regularly in the environment.”
Dr. VanWagner, who was not involved in the study, said the major limitation is the small number of human studies and the high heterogeneity between studies, “meaning it is hard to come to a firm conclusion about whether what has been observed in the animal studies does truly apply to humans.
“Overall, this study provides important proof of concept for future work to look more specifically at PFAS exposure, and more specific markers of fatty liver disease and liver damage, like liver biopsy, are needed in humans,” Dr. VanWagner said.
“If data accumulate showing that these chemicals do in fact contribute to fatty liver and worsening inflammation or liver damage as a result of exposure, then public health interventions to remove or reduce use of these chemicals could have wide-ranging public health effects,” Dr. VanWagner added.
Further research needed
The authors of an invited perspective published with the study say it underscores the “urgent need for further research and for immediate and reasonable public health action.”
“This work firmly puts PFAS exposure on the list of persistent pollutants, such as polychlorinated biphenyls, that cause hepatotoxicity and whose mechanism is linked to steatosis,” write Alan Ducatman, MD. MSc, with West Virginia University School of Public Health, Morgantown, and Suzanne Fenton, PhD, MS, with the National Institute of Environmental Health Sciences, Research Triangle Park, N.C.
They say other important questions raised by this review include whether individuals who are overweight or obese and those with diabetes are more susceptible to PFAS hepatoxicity, which “replacement” or emerging PFAS can cause liver damage, and whether high doses cause different kinds of liver toxicity than low doses.
“GenX, a current replacement [chemical] for PFOA, has shown significant hepatotoxicity in several recent experimental studies, suggesting it may not be a safe replacement,” they point out.
“A significant challenge will be deciding which of the multiple metabolic pathways altered by PFAS are most important and predictive for induction of liver damage and for progression of liver disease, so that emerging PFAS may be screened for hepatotoxicity prior to entering the market,” Dr. Ducatman and Dr. Fenton conclude.
Support for this research was provided by the National Institute of Environmental Health Science, part of the National Institutes of Health, and the U.S. Department of Agriculture National Institute of Food and Agriculture. Dr. Costello, Dr. VanWagner, Dr. Ducatman, and Dr. Fenton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(NAFLD), say the authors of a comprehensive evidence review.
They found “consistent” evidence for PFAS hepatotoxicity from rodent studies. In addition, exposure to PFAS was found to be associated with markers of liver function in observational studies in people.
The review, published online in Environmental Health Perspectives, may be the first systematic analysis of PFAS exposure and liver damage.
Possible contributor to growing NAFLD epidemic
In their analysis, the authors included 85 rodent studies and 24 epidemiologic studies, primarily involving people from the United States and largely focusing on four “legacy” PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS).
Meta-analyses of human studies found that higher levels of alanine aminotransferase were significantly associated with exposure to three of the older chemicals – PFOA, PFOS, and PFNA.
The “positive” and “convincing” associations between exposure to these synthetic chemicals and higher ALT levels suggest that exposure may contribute to the growing NAFLD epidemic, the researchers write.
Exposure to one of the chemicals, PFOA, was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in people.
In rodents, exposure to these synthetic chemicals consistently resulted in higher ALT levels and steatosis.
“The mechanism is not well understood yet, but there are a few proposed theories,” first author Elizabeth Costello, MPH, PhD student, department of population and public health sciences, University of Southern California, Los Angeles, told this news organization.
“PFAS are similar to fatty acids in chemical structure, so it’s possible that they activate some of the same receptors or otherwise interfere with fat metabolism. This might lead to inflammation or fat accumulation in the liver,” Ms. Costello explained.
People widely exposed
PFAS are ubiquitous in the environment. They have been detected in the blood of most people and have been linked to a variety of health concerns. Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
“We are exposed to PFAS in so many ways – through water, food, and products we use. It can be very difficult for individuals to control their own exposure,” Ms. Costello commented.
“At this point, it’s important to look for ways to remove PFAS from the environment and phase them out of our products and carefully consider the safety of any replacement chemicals,” she said.
Although most of the research to date has been limited to the four older PFAS (PFOA, PFOS, PFNA, and PFHxS), there are thousands of different PFAS chemicals.
“We don’t know very much about the effects of exposure to multiple PFAS at the same time or how newer replacement PFAS might affect liver disease or other health conditions,” Ms. Costello said.
Reached for comment, Lisa B. VanWagner, MD, with Northwestern University, Chicago, said this analysis is “very interesting,” but she is also “left wondering how we could do anything since it seems from my reading that these chemicals are ubiquitous and used regularly in the environment.”
Dr. VanWagner, who was not involved in the study, said the major limitation is the small number of human studies and the high heterogeneity between studies, “meaning it is hard to come to a firm conclusion about whether what has been observed in the animal studies does truly apply to humans.
“Overall, this study provides important proof of concept for future work to look more specifically at PFAS exposure, and more specific markers of fatty liver disease and liver damage, like liver biopsy, are needed in humans,” Dr. VanWagner said.
“If data accumulate showing that these chemicals do in fact contribute to fatty liver and worsening inflammation or liver damage as a result of exposure, then public health interventions to remove or reduce use of these chemicals could have wide-ranging public health effects,” Dr. VanWagner added.
Further research needed
The authors of an invited perspective published with the study say it underscores the “urgent need for further research and for immediate and reasonable public health action.”
“This work firmly puts PFAS exposure on the list of persistent pollutants, such as polychlorinated biphenyls, that cause hepatotoxicity and whose mechanism is linked to steatosis,” write Alan Ducatman, MD. MSc, with West Virginia University School of Public Health, Morgantown, and Suzanne Fenton, PhD, MS, with the National Institute of Environmental Health Sciences, Research Triangle Park, N.C.
They say other important questions raised by this review include whether individuals who are overweight or obese and those with diabetes are more susceptible to PFAS hepatoxicity, which “replacement” or emerging PFAS can cause liver damage, and whether high doses cause different kinds of liver toxicity than low doses.
“GenX, a current replacement [chemical] for PFOA, has shown significant hepatotoxicity in several recent experimental studies, suggesting it may not be a safe replacement,” they point out.
“A significant challenge will be deciding which of the multiple metabolic pathways altered by PFAS are most important and predictive for induction of liver damage and for progression of liver disease, so that emerging PFAS may be screened for hepatotoxicity prior to entering the market,” Dr. Ducatman and Dr. Fenton conclude.
Support for this research was provided by the National Institute of Environmental Health Science, part of the National Institutes of Health, and the U.S. Department of Agriculture National Institute of Food and Agriculture. Dr. Costello, Dr. VanWagner, Dr. Ducatman, and Dr. Fenton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(NAFLD), say the authors of a comprehensive evidence review.
They found “consistent” evidence for PFAS hepatotoxicity from rodent studies. In addition, exposure to PFAS was found to be associated with markers of liver function in observational studies in people.
The review, published online in Environmental Health Perspectives, may be the first systematic analysis of PFAS exposure and liver damage.
Possible contributor to growing NAFLD epidemic
In their analysis, the authors included 85 rodent studies and 24 epidemiologic studies, primarily involving people from the United States and largely focusing on four “legacy” PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS).
Meta-analyses of human studies found that higher levels of alanine aminotransferase were significantly associated with exposure to three of the older chemicals – PFOA, PFOS, and PFNA.
The “positive” and “convincing” associations between exposure to these synthetic chemicals and higher ALT levels suggest that exposure may contribute to the growing NAFLD epidemic, the researchers write.
Exposure to one of the chemicals, PFOA, was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in people.
In rodents, exposure to these synthetic chemicals consistently resulted in higher ALT levels and steatosis.
“The mechanism is not well understood yet, but there are a few proposed theories,” first author Elizabeth Costello, MPH, PhD student, department of population and public health sciences, University of Southern California, Los Angeles, told this news organization.
“PFAS are similar to fatty acids in chemical structure, so it’s possible that they activate some of the same receptors or otherwise interfere with fat metabolism. This might lead to inflammation or fat accumulation in the liver,” Ms. Costello explained.
People widely exposed
PFAS are ubiquitous in the environment. They have been detected in the blood of most people and have been linked to a variety of health concerns. Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
“We are exposed to PFAS in so many ways – through water, food, and products we use. It can be very difficult for individuals to control their own exposure,” Ms. Costello commented.
“At this point, it’s important to look for ways to remove PFAS from the environment and phase them out of our products and carefully consider the safety of any replacement chemicals,” she said.
Although most of the research to date has been limited to the four older PFAS (PFOA, PFOS, PFNA, and PFHxS), there are thousands of different PFAS chemicals.
“We don’t know very much about the effects of exposure to multiple PFAS at the same time or how newer replacement PFAS might affect liver disease or other health conditions,” Ms. Costello said.
Reached for comment, Lisa B. VanWagner, MD, with Northwestern University, Chicago, said this analysis is “very interesting,” but she is also “left wondering how we could do anything since it seems from my reading that these chemicals are ubiquitous and used regularly in the environment.”
Dr. VanWagner, who was not involved in the study, said the major limitation is the small number of human studies and the high heterogeneity between studies, “meaning it is hard to come to a firm conclusion about whether what has been observed in the animal studies does truly apply to humans.
“Overall, this study provides important proof of concept for future work to look more specifically at PFAS exposure, and more specific markers of fatty liver disease and liver damage, like liver biopsy, are needed in humans,” Dr. VanWagner said.
“If data accumulate showing that these chemicals do in fact contribute to fatty liver and worsening inflammation or liver damage as a result of exposure, then public health interventions to remove or reduce use of these chemicals could have wide-ranging public health effects,” Dr. VanWagner added.
Further research needed
The authors of an invited perspective published with the study say it underscores the “urgent need for further research and for immediate and reasonable public health action.”
“This work firmly puts PFAS exposure on the list of persistent pollutants, such as polychlorinated biphenyls, that cause hepatotoxicity and whose mechanism is linked to steatosis,” write Alan Ducatman, MD. MSc, with West Virginia University School of Public Health, Morgantown, and Suzanne Fenton, PhD, MS, with the National Institute of Environmental Health Sciences, Research Triangle Park, N.C.
They say other important questions raised by this review include whether individuals who are overweight or obese and those with diabetes are more susceptible to PFAS hepatoxicity, which “replacement” or emerging PFAS can cause liver damage, and whether high doses cause different kinds of liver toxicity than low doses.
“GenX, a current replacement [chemical] for PFOA, has shown significant hepatotoxicity in several recent experimental studies, suggesting it may not be a safe replacement,” they point out.
“A significant challenge will be deciding which of the multiple metabolic pathways altered by PFAS are most important and predictive for induction of liver damage and for progression of liver disease, so that emerging PFAS may be screened for hepatotoxicity prior to entering the market,” Dr. Ducatman and Dr. Fenton conclude.
Support for this research was provided by the National Institute of Environmental Health Science, part of the National Institutes of Health, and the U.S. Department of Agriculture National Institute of Food and Agriculture. Dr. Costello, Dr. VanWagner, Dr. Ducatman, and Dr. Fenton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENVIRONMENTAL HEALTH PERSPECTIVES
New data confirm risk of Guillain-Barré with J&J COVID shot
The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.
The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.
“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.
“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.
The study was published online in JAMA Network Open.
Eleven cases
Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.
This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.
The researchers confirmed 11 cases of GBS after the Janssen vaccine.
The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.
There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.
In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.
Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.
The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
Novel presentation?
The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.
“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.
“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.
This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.
A version of this article first appeared on Medscape.com.
The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.
The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.
“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.
“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.
The study was published online in JAMA Network Open.
Eleven cases
Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.
This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.
The researchers confirmed 11 cases of GBS after the Janssen vaccine.
The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.
There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.
In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.
Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.
The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
Novel presentation?
The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.
“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.
“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.
This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.
A version of this article first appeared on Medscape.com.
The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.
The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.
“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.
“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.
The study was published online in JAMA Network Open.
Eleven cases
Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.
This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.
The researchers confirmed 11 cases of GBS after the Janssen vaccine.
The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.
There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.
In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.
Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.
The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
Novel presentation?
The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.
“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.
“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.
This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
New blood biomarker to detect early dementia?
Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.
“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.
If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”
The study was published online in PLOS ONE.
New drug target?
The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).
The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.
This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.
The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.
Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.
“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.
The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.
“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
Caveats, cautionary notes
Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”
Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”
She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.
For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”
“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.
“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”
This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.
“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.
If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”
The study was published online in PLOS ONE.
New drug target?
The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).
The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.
This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.
The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.
Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.
“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.
The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.
“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
Caveats, cautionary notes
Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”
Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”
She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.
For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”
“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.
“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”
This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.
“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.
If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”
The study was published online in PLOS ONE.
New drug target?
The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).
The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.
This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.
The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.
Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.
“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.
The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.
“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
Caveats, cautionary notes
Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”
Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”
She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.
For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”
“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.
“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”
This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FDA clears mavacamten (Camzyos) for obstructive hypertrophic cardiomyopathy
The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).
Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.
“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
‘Revolutionary’ change
The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.
In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.
The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.
Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.
“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.
The product information for mavacamten includes a boxed warning citing a risk for heart failure.
Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.
Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.
Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).
Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.
“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
‘Revolutionary’ change
The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.
In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.
The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.
Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.
“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.
The product information for mavacamten includes a boxed warning citing a risk for heart failure.
Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.
Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.
Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).
Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.
“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
‘Revolutionary’ change
The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.
In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.
The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.
Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.
“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.
The product information for mavacamten includes a boxed warning citing a risk for heart failure.
Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.
Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.
Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
FDA warns of pump defect with Medtronic HVAD system
Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals.
Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.
The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.
This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.
Pump thrombosis
Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.
All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.
Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.
The FDA does not recommend the elective removal of properly functioning systems.
“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.
Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.
If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.
For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.
The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.
Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals.
Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.
The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.
This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.
Pump thrombosis
Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.
All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.
Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.
The FDA does not recommend the elective removal of properly functioning systems.
“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.
Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.
If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.
For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.
The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.
Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals.
Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.
The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.
This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.
Pump thrombosis
Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.
All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.
Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.
The FDA does not recommend the elective removal of properly functioning systems.
“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.
Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.
If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.
For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.
The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.
Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.