Pharmacology

TOPLINE:

Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.

METHODOLOGY:

• Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
• In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
• In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
• They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.

TAKEAWAY:

• Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
• Galantamine dietary supplements, however, showed a wide variance in content, ranging from less than 2% to 110% of the labeled amount, and 30% were contaminated with Bacillus cereus sensu stricto. The amount of bacteria present would not have been expected to harm consumers, according to the authors of the study.

IN PRACTICE:

“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.

SOURCE:

The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.

LIMITATIONS:

The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.

DISCLOSURES:

Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.

METHODOLOGY:

• Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
• In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
• In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
• They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.

TAKEAWAY:

• Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
• Galantamine dietary supplements, however, showed a wide variance in content, ranging from less than 2% to 110% of the labeled amount, and 30% were contaminated with Bacillus cereus sensu stricto. The amount of bacteria present would not have been expected to harm consumers, according to the authors of the study.

IN PRACTICE:

“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.

SOURCE:

The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.

LIMITATIONS:

The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.

DISCLOSURES:

Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.

METHODOLOGY:

• Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
• In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
• In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
• They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.

TAKEAWAY:

• Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
• Galantamine dietary supplements, however, showed a wide variance in content, ranging from less than 2% to 110% of the labeled amount, and 30% were contaminated with Bacillus cereus sensu stricto. The amount of bacteria present would not have been expected to harm consumers, according to the authors of the study.

IN PRACTICE:

“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.

SOURCE:

The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.

LIMITATIONS:

The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.

DISCLOSURES:

Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

Will the new US Department of Veterans Affairs (VA) pharmacy software be safe and effective? That was the topic when David Case, the VA Deputy Inspector General, spoke in the US House of Representatives Veterans Affairs Committee technology modernization subcommittee hearing on February 15.

Questions like that have dogged the project since 2018, when the VA began rolling out the Oracle Cerner electronic health record (EHR) system as the successor to ViSTA.

The Oracle system has been beset by one glitch after another since its arrival. And in that time, Case said, the VA Office of Inspector General (OIG) has been engaging with VA employees at sites in Washington, Oregon, Ohio, Illinois, and other locations where the modernization program has been piloted.

The most recent OIG investigation of pharmacy-related patient safety issues began with a review of an allegation of a prescription backlog at Columbus, Ohio, where the system went live on April 30, 2022. The OIG found that facility leaders took “timely and sustainable steps” to manage that issue. However, other unresolved patient safety issues came to light, such as medication inaccuracies, inaccurate medication data, and insufficient staffing. The OIG also found staff were creating “numerous work arounds” to provide patient care, and that the volume of staff educational materials for pharmacy-related functions was “overwhelming.”

Those problems were just the latest in a long queue. In May 2021, after the first VA deployment of the new EHR at the Mann-Grandstaff VA Medical Center in Spokane, Washington, a pharmacy patient safety team under the VA National Center for Patient Safety (NCPS) also had identified patient safety issues and “multiple” concerns regarding the system’s usability. For example, updates to a patient’s active medication list were not routinely reflected at the patient’s next appointment. Despite knowing about such challenges, Case noted in his report, VA leaders deployed the new EHR at 4 more VA medical centers.

Cerner/ViSTA Communication

One major cause of the current problems is the way the systems “talk” to each other. EHR information is communicated between VHA facilities through channels that include the Joint Longitudinal Viewer (JLV) and the Health Data Repository, which stores patient-specific clinical information from both the legacy and the new EHR systems. The JLV application allows clinicians to access a read only version of a patient’s EHR from both systems.

Every medication used in VHA has a VA Unique Identifier (VUID). When a patient is prescribed a medication at a new EHR site, that medication’s VUID is sent to the Health Data Repository. If that patient seeks care from a legacy health care practitioner (HCP), and that HCP enters a medication order, a software interface accesses the VUID from the Health Data Repository to verify that the medication being prescribed is safe and compatible with the medications and allergies previously documented in the patient’s record.

However, on March 31, 2023, staff from a ViSTA site found an incorrect medication order when prescribing a new medication to a patient who had received care and medications at a new EHR site. This in turn led to the discovery that an error in Oracle software coding had resulted in the “widespread transmission” of incorrect VUIDs from new EHR sites to legacy EHR sites, the OIG found. VA leaders and HCPs were notified of the potential clinical impact and were given specific instructions on how to mitigate the issue. They were asked to “please share widely.”

On top of that, days later, patient safety managers across the Veterans Health Administration (VHA) were told that drug-to-drug interactions, duplicate medication orders, and allergy checks were not functioning as expected, and they too were provided with remedial actions.

Oracle applied a successful software patch on in April 2023, to ensure accurate VUIDs were attached to all mail order pharmacy–processed prescriptions from that date forward. However, the OIG learned the incorrect VUIDs sent from new EHR sites and stored in the Health Data Repository from as far back as October 2020 had not been corrected. Case told the subcommittee that on November 29, 2023, the VHA Pharmacy Council reported withdrawing a request for Oracle to send corrected medication VUID data to the Health Data Repository, on the presumption that remaining inaccurate VUIDs would expire in early April 2024, and the data would be corrected at that time.

The OIG is concerned, Case said, that patient medication data remains inaccurate almost a year after VA learned of the issue. The mail order pharmacy-related data generated from approximately 120,000 patients served by new EHR sites are still incorrect. These patients face an ongoing risk of an adverse medication-related event if they receive care and medications from a VA medical center using the legacy EHR system.

The OIG also learned of other problems associated with transmission of medication and allergy information, which could have consequences such as:

• Patient medications being discontinued or stopped by new HCPs using Cerner that appear in ViSTA as active and current prescriptions;
• Allergy-warning messages not appearing when intended or inappropriately appearing for the wrong medication;
• Duplicate medication order checks not appearing when intended or inappropriately appearing for the wrong drug;
• Patient active medication lists having incomplete or inaccurate information, such as missing prescriptions, duplicate prescriptions, or incorrect medication order statuses.

The OIG warned VHA employees about the risks, although it wasn’t possible to determine who might actually be at risk. A VHA leader told the OIG that all patients who have been prescribed any medications or have medication allergies documented at a at a Cerner site are at risk. That could mean as many as 250,000 patients: As of September 2023, approximately 190,000 patients had a medication prescribed and 126,000 had an allergy documented at a new EHR site.

Case Example

Not surprisingly, “the OIG is not confident in [EHRM-Integration Office] leaders’ oversight and control of the new systems’ Health Data Repository interface programming,” Case said. He cited the case of a patient with posttraumatic stress disorder and traumatic brain injury with adrenal insufficiency. Four days prior to admission, a ViSTA site pharmacist used the EHR to perform a medication reconciliation for the patient. The data available did not include the patient’s most recent prednisone prescription, which had been ordered by an HCP at a facility using Cerner.

A nurse practitioner performed another reconciliation when the patient was admitted to the residential program, but the patient was unsure of all their medications. Because the most recent prednisone prescription was not visible in ViSTA, the prednisone appeared to have been completed at least 3 months prior to admission and was therefore not prescribed in the admission medication orders.

Five days into the residential program, the patient began exhibiting unusual behaviors associated with the lack of prednisone. The patient realized they needed more prednisone, but the nurse explained there was no prednisone on the patient’s medication list. Eventually, the patient found the active prednisone order on their personal cell phone and was transferred to a local emergency department for care.

Work Arounds

The VHA’s efforts to forestall or mitigate system errors have in some cases had a cascade effect. For example, HCPs must essentially back up what the automated software is intended to do, with “complex, time-consuming” multistep manual safety checks when prescribing new medications for patients previously cared for at a Cerner site. The OIG is concerned that this increased vigilance is “unsustainable” by pharmacists and frontline staff and could lead to burnout and medication-related patient safety events. After the new EHR launched, the OIG found, burnout symptoms for pharmacy staff increased. Nonetheless, Case told the committee, OIG staff “have observed [employees’] unwavering commitment to prioritizing the care of patients while mitigating implementation challenges.”

EHR-related workload burdens have necessitated other adjustments. Columbus, for instance, hired 9 full-time clinical pharmacists—a 62% staffing increase—to help reduce the backlog. Pharmacy leaders created approximately 29 additional work-arounds to support pharmacy staff and prevent delays. Facility pharmacy leaders also developed approximately 25 educational materials, such as tip sheets, reference guides, and job aids. The OIG’s concern—apart from the overwhelming amount of information for staff to implement—is that such prophylactic measures may in fact give rise to inconsistent practices, which increase risks to patient safety.

Committed to Working With the VA

Mike Sicilia, executive vice president of Oracle Corporation, told lawmakers in the hearing, “After the initial deployments, it became clear that the pharmacy system needed to be enhanced to better meet VA’s needs. To that end, in August 2022, shortly after Oracle completed its acquisition of Cerner, VA contracted with us for seven enhancements that overall would adapt the pharmacy system to a more bidirectional system between VA providers placing prescription orders and VA pharmacists fulfilling and dispensing them.” Those enhancements are all live for VA providers and pharmacists to use now, he said, except for one that is undergoing additional testing.

He added, “As with any healthcare technology system, there is a need for continuous improvements but that does not mean the system is not safe and effective in its current state. Oracle is committed to working with VA … throughout the reset period to identify workflows and other items that can be simplified or streamlined to improve the overall user and pharmacy experience.”

Standardizing workflows and ensuring training and communications to pharmacists about the latest updates will discourage use of work-arounds, Sicilia said, and “help with improving morale and satisfaction with the system.” During a visit in early February by VA and the Oracle team to the Lovell Federal Health Care Center in North Chicago, “feedback from pharmacists was positive about the training and readiness for using the new pharmacy system.”

The backlog, at least, may be resolved. Sicilia said on average more than 215,000 outpatient prescriptions are being filled each month. “The current live sites do not have a backlog in filling prescriptions. Recent data from this month show that three of the five live sites have zero prescriptions waiting to be processed that are older than seven days. The two other live sites have an average of two prescriptions older than seven days,” he said.

Although Oracle Health has since resolved some of the identified issues, the OIG is concerned that the new EHR will continue to be deployed at medical facilities despite “myriad” as-yet unresolved issues related to inaccurate medication ordering, reconciliation, and dispensing. The VHA has paused Cerner deployments multiple times.

“It is unclear whether identified problems are being adequately resolved before additional deployments,” Case said. “There is also the question of whether there is sufficient transparency and communication among EHRM-IO, VHA and facility leaders, VA leaders, and Oracle Health needed for quality control and critical coordination. Trust in VA is also dependent on patients being fully and quickly advised when issues affecting them are identified and addressed. As VA moves toward its deployment next month at a complex facility jointly operated with the Department of Defense, transparency, communication, and program management will be essential to getting it right. Failures in these areas risk cascading problems.”

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lifileucel (Amtagvi, Iovance Biotherapeutics) for the treatment of certain adults with unresectable or metastatic melanoma, marking the first approval of a cellular therapy in the solid tumor setting.

Specifically, the tumor-derived autologous T-cell immunotherapy is indicated for adult patients previously treated with a programmed cell death protein 1 (PD-1)–blocking antibody, and if BRAF V600–positive, a BRAF inhibitor with or without an MEK inhibitor. 

The approval “offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” Samantha R. Guild, JD, president, AIM at Melanoma Foundation, stated in a press release. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”

The approval was based on findings from the open-label single-arm global C-144-01 clinical trial, which showed an objective response rate of 31.5% in 73 patients treated within the recommended dosing rage of 7.5 x 109 to 72 x 109 viable cells. Complete responses occurred in three patients (4.1%) and partial responses occurred in 20 patients (27.4%)

Median duration of response was not reached at 18.6 months of follow-up. The median time to initial response to the therapy was 1.5 months, according to an FDA press release.

“Unresectable or metastatic melanoma is an aggressive form of cancer that can be fatal,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research stated in the FDA release. “The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T cell immunotherapy for patients with limited treatment options.”

“The melanoma community is so grateful to the patients, caregivers, and clinicians who have made the clinical trials of this therapy possible and got lifileucel to approval,” Allison Betof Warner, MD, PhD, director of Melanoma Medical Oncology at Stanford Medicine, wrote on X. “We are very excited to bring this life-saving therapy to patients ASAP! Available immediately at @StanfordCancer!!!”

For the C-144-01 trial, lifileucel was administered after a lymphodepletion regimen of 60 mg/kg/d of cyclophosphamide for 2 days followed by 25 mg/m2/d of fludarabine for 5 days. Between 3 and 34 hours after infusion, patients received 600,000 IU/Kg of the interleukin 2 aldesleukin every 8-12 hours for up to six doses to support cell expansion in vivo. 

The full prescribing information for lifileucel contains a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions, which occurred in at least 20% of patients, were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

“Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated,” according to the FDA statement.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved omalizumab (Xolair, Genentech) for reducing allergic reactions to foods in adults and most children. The drug is meant to be taken regularly by patients with food allergies to reduce the risk for reactions, including anaphylaxis, in case of accidental exposure to one or more allergens. The injection is not approved for emergency treatment of an allergic reaction.

Omalizumab first was approved for persistent allergic asthma in 2003. It also is approved for chronic spontaneous urticaria and chronic rhinosinusitis with nasal polyps. 

The new indication for immunoglobulin E–mediated food allergy in adults and children aged 1 year or older makes omalizumab the first drug approved to mitigate allergic reactions to more than one food, the FDA said. Peanut-allergen powder (Palforzia) can reduce reactions to peanut, but its benefits are limited to that allergy.

“While it will not eliminate food allergies or allow patients to consume food allergens freely, its repeated use will help reduce the health impact if accidental exposure occurs,” said Kelly Stone, MD, PhD, associate director of the division of pulmonology, allergy, and critical care in the FDA’s Center for Drug Evaluation and Research, in a news release. 

The safety and efficacy of the monoclonal antibody in reducing allergic reactions was studied in a double-blind, placebo-controlled study of 168 children and adults who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Patients received omalizumab or placebo for 16-20 weeks. At the end of the study, patients consumed peanut protein (equivalent to 2.5 peanuts). Of those who received the drug, 68% were able to consume peanut without moderate or severe allergic symptoms, versus 6% in the placebo group.

More patients who received the medication also avoided moderate or severe reactions to cashews (42% vs 3%), milk (66% vs 11%), and eggs (67% vs 0%). 

The most common side effects of omalizumab included injection site reactions and fever. The drug’s label includes warnings and precautions about anaphylaxis, cancer, fever, joint pain, rash, parasitic (worm) infection, and abnormal laboratory tests. Omalizumab comes with a boxed warning for anaphylaxis and should be started only in a healthcare setting equipped to manage anaphylaxis, according to the FDA.

A version of this article appeared on Medscape.com.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

Prednisolone may be an effective bridge therapy to ease withdrawal symptoms and improve reversal for patients with migraine whose headaches persist despite them taking an abundance of acute headache medications, a condition known as medication-overuse headache (MOH), an observational study out of South Korea has found.

The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)  

Seoul National Univeristy College of Medicine

The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
 

Study methods

The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.

The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.

Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.

Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.

The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.

Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
 

Commentary

Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.

Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.

“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”

He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.

Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.