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Self-worth training boosts ketamine’s effects in severe depression
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY
New deep dive into Paxlovid interactions with CVD meds
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
FDA confirms nationwide Adderall shortage
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration which are approved for treating attention deficit hyperactivity disorder and narcolepsy.
The FDA announcement follows weeks of reports of a shortage of the drug by pharmacy chains and Adderall users.
The agency said it is in “frequent” contact with all manufacturers of Adderall – and reported that one of those companies, Teva, is experiencing ongoing intermittent manufacturing delays.
Other manufacturers continue to produce amphetamine mixed salts, but there is not enough supply to continue to meet U.S. market demand through those producers, the FDA noted.
“Until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to health care professionals and their patients for amphetamine mixed salts’ approved indications,” the agency said.
Patients should work with their health care provider to determine their best treatment option, it added.
The organization is continuing to monitor the supply of Adderall and to help manufacturers resolve the shortage.
Its Drug Shortage webpage has additional information about the situation and is updated regularly.
“We continue to use all the tools we have available to help keep supply available for patients and will provide public updates regarding the Adderall shortage,” the FDA said.
A version of this article first appeared on Medscape.com.
Dermatologists fear effects of Dobbs decision for patients on isotretinoin, methotrexate
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.
The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.
As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.
“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.
The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.
But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”
The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
Methotrexate prescriptions
Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.
The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”
“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”
The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.
Perspective: A Georgia dermatologist
Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.
That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.
In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.
Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”
Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
Perspective: An Arizona dermatologist
Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.
And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.
Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
Perspective: A Connecticut dermatologist
The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.
Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”
For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.
Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”
Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
Need for EC education
In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.
The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.
Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Tirzepatide’s benefits expand: Lean mass up, serum lipids down
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
AT EASD 2022
Older diabetes drugs linked to dementia risk -- one lower, one higher
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.
Opposite effects of sulfonylureas, TZDs versus metformin
The study authors analyzed 559,106 VA patients with type 2 diabetes who initiated glucose-lowering medication during 2001-2017 and took it for at least a year. They were aged 60 years or older and did not have dementia at baseline. Most were White (76.8%) and male (96.9%), two-thirds (63.1%) had obesity, and mean hemoglobin A1c was 6.8%.
Overall, 31,125 developed all-cause dementia. The incidence rate was 8.2 cases per 1,000 person-years, ranging from 6.2 cases per 1,000 person-years among those taking metformin monotherapy to 13.4 cases per 1,000 person-years in those taking both sulfonylurea and a TZD.
Compared with metformin monotherapy, the hazard ratio for all-cause dementia for sulfonylurea monotherapy was a significant 1.12. The increased risk was also seen for vascular dementia, with an HR of 1.14.
In contrast, TZD monotherapy was associated with a significantly lower risk for all-cause dementia (HR, 0.78), as well as for Alzheimer’s disease (HR, 0.89) and vascular dementia (HR, 0.43), compared with metformin monotherapy.
The combination of metformin and TZD also lowered the risk of all-cause dementia, while regimens including sulfonylureas raised the risks for all-cause and vascular dementia.
Most of the results didn’t change significantly when the drug exposure window was extended to 2 years.
Effects more pronounced in those with obesity
The protective 1-year effects of TZD monotherapy and of metformin plus TZD, compared with metformin alone, were more significant among participants aged 75 or younger and with a body mass index above 25 kg/m2, compared with those who were older than 75 years and with normal BMIs, respectively.
On the other hand, the greater risk for dementia incurred with sulfonylureas was further increased among those with higher BMI.
This research was partially funded by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute. Dr. Koychev is chief investigator for a trial, sponsored by Oxford University and funded by Novo Nordisk, testing whether the GLP-1 agonist semaglutide reduces the risk for dementia in aging adults.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN DIABETES RESEARCH & CARE
Dapagliflozin DELIVERs regardless of systolic pressure in HFpEF
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Evusheld PrEP may protect immunocompromised patients from severe COVID-19
Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.
Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.
“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.
“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.
“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.
“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.
For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
EVUSHELD was well tolerated
After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.
All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:
- Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
- Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
- Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
- One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.
Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.
“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.
“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.
“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.
Evusheld not always easy to obtain
Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.
“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.
“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.
Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.
Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.
“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.
“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.
“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”
Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.
FDA: Evusheld may not neutralize certain SARS-CoV-2 variants
“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.
In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.
There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.
Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.
Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.
“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.
“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.
“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.
“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.
For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
EVUSHELD was well tolerated
After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.
All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:
- Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
- Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
- Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
- One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.
Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.
“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.
“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.
“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.
Evusheld not always easy to obtain
Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.
“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.
“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.
Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.
Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.
“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.
“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.
“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”
Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.
FDA: Evusheld may not neutralize certain SARS-CoV-2 variants
“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.
In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.
There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.
Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.
Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.
“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.
“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.
“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.
“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.
For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
EVUSHELD was well tolerated
After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.
All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:
- Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
- Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
- Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
- One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.
Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.
“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.
“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.
“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.
Evusheld not always easy to obtain
Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.
“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.
“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.
Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.
Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.
“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.
“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.
“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”
Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.
FDA: Evusheld may not neutralize certain SARS-CoV-2 variants
“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.
In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.
There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.
FROM RMD OPEN
Gardasil 9 HPV vaccine advised for MSM living with HIV
Men who have sex with men (MSM) living with HIV, especially those who are young or who’ve had gonorrhea, should get the human papillomavirus (HPV) 9-valent vaccine (Gardasil 9), findings of a newly published study in the Journal of Acquired Immune Deficiency Syndromes suggest.
According to the World Health Organization, only 30% of the target population worldwide has received the HPV vaccine. Despite increased risk for HPV anal infection (an estimated three out of four MSM develop an anal infection from any HPV genotype in their lifetime, epidemiological studies in MSM have been lacking, leaving gaps in data in terms of prevalence rates and prevention.
To help characterize which MSM subgroups benefit the most from early 9-valent HPV vaccination, researchers from Vita-Salute San Raffaele University in Milan determined the prevalence of anal HPV genotypes in MSM who’d been living with HIV for 5 years, and they analyzed the risk factors for HPV anal infection.
Of the 1,352 study participants, 12% were not infected by any HPV genotypes, and the maximum number of genotypes infecting one person (six) was detected in 0.4% (six) people. The prevalence of HR-HPV genotypes or those present in the vaccine remained stable over time.
“Our findings suggest ... that all MSM with HIV would benefit from Gardasil 9 immunization, particularly the youngest and those with a prior gonococcal infection,” wrote Elena Bruzzesi, MD, of Vita-Salute San Raffaele University, and her coauthors.
To determine prevalence of HPV genotypes at anal sites and risk factors, the authors conducted a time-trend, monocentric study on participants who self-identified as MSM who engaged in anal intercourse. The participants underwent one or more anoscopies for HPV genotyping at one academic hospital in Milan between 2015 and 2019.
Swab specimens were collected from the anal canal mucosa, then soaked in thin-layer liquid medium, and sent for molecular analysis.
For detection of HPV phenotypes, the specimens were processed by multiplex real-time polymerase chain reaction.
Findings showed that:
- The overall prevalence of MSM with at least one anal HPV genotype was 88%, with prevalence ranging from 77% to 84%, and no trend difference over the 5-year period.
- Seventy-nine percent of participants were exposed to at least one high-risk (HR)-HPV genotype, and 67.4% by at least one low-risk (LR)-HPV genotype.
- HPV-53, in 27%, was the most prevalent genotype. HPV-6, 11, 16, and 18 prevalence was 22%, 13%, 23%, and 11%, respectively. Of the HR genotypes, HPV-16 and HPV-18 are most often linked with squamous cell cancers and adenocarcinomas, and in the study, prevalence did not change over time.
- Seventy-one percent of participants carried at least one genotype covered by the vaccine, with no change over time.
- On multivariable analysis, the risk of carrying at least one high-risk HPV genotype was linked with younger age (adjusted odds ratio [aOR] for 30 years or younger compared with older than 45 years 2.714; 95% confidence interval [CI], 1.484-4.961), and with having had gonorrhea (aOR, 2.118; 95% CI, 1.100-4.078).
- Also on multivariable analysis, the risk of having one or more genotypes targeted by the 9-valent vaccine was linked with younger age (aOR, 1.868; 95% CI, 1.141-3.060) and with having had gonorrhea (aOR, 1.785; 95% CI, 1.056-3.018).
Mehri S. McKellar, MD, an infectious disease specialist at Duke Health in Durham, N.C., told this news organization.
“This powerful study provides important data on HPV genotype prevalence in the MSM HIV+ population, validating that Gardasil 9 will greatly help these individuals,” said Dr. McKellar, who was not involved in the study.
Robert Salata, MD, infectious disease specialist and professor at Case Western Reserve University, Cleveland, also encourages MSM to get the vaccine.
“It is important to understand that the prevalence of anal HPV in men who have sex with men is very high, that the prevalence, including high-risk genotypes, has remained stable, and that the 9-valent vaccine is clearly indicated, especially in younger men and those with known gonorrhea and other STDs,” Dr. Salata (who was also not involved in the study) told this news organization.
“This is an important reminder for us to continue promoting and providing the vaccine to our patients, especially to HIV+ men who have sex with men, who have the highest rates of anal infection with HPV,” Dr. McKellar advised.
The authors, Dr. McKellar, and Dr. Salata report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Men who have sex with men (MSM) living with HIV, especially those who are young or who’ve had gonorrhea, should get the human papillomavirus (HPV) 9-valent vaccine (Gardasil 9), findings of a newly published study in the Journal of Acquired Immune Deficiency Syndromes suggest.
According to the World Health Organization, only 30% of the target population worldwide has received the HPV vaccine. Despite increased risk for HPV anal infection (an estimated three out of four MSM develop an anal infection from any HPV genotype in their lifetime, epidemiological studies in MSM have been lacking, leaving gaps in data in terms of prevalence rates and prevention.
To help characterize which MSM subgroups benefit the most from early 9-valent HPV vaccination, researchers from Vita-Salute San Raffaele University in Milan determined the prevalence of anal HPV genotypes in MSM who’d been living with HIV for 5 years, and they analyzed the risk factors for HPV anal infection.
Of the 1,352 study participants, 12% were not infected by any HPV genotypes, and the maximum number of genotypes infecting one person (six) was detected in 0.4% (six) people. The prevalence of HR-HPV genotypes or those present in the vaccine remained stable over time.
“Our findings suggest ... that all MSM with HIV would benefit from Gardasil 9 immunization, particularly the youngest and those with a prior gonococcal infection,” wrote Elena Bruzzesi, MD, of Vita-Salute San Raffaele University, and her coauthors.
To determine prevalence of HPV genotypes at anal sites and risk factors, the authors conducted a time-trend, monocentric study on participants who self-identified as MSM who engaged in anal intercourse. The participants underwent one or more anoscopies for HPV genotyping at one academic hospital in Milan between 2015 and 2019.
Swab specimens were collected from the anal canal mucosa, then soaked in thin-layer liquid medium, and sent for molecular analysis.
For detection of HPV phenotypes, the specimens were processed by multiplex real-time polymerase chain reaction.
Findings showed that:
- The overall prevalence of MSM with at least one anal HPV genotype was 88%, with prevalence ranging from 77% to 84%, and no trend difference over the 5-year period.
- Seventy-nine percent of participants were exposed to at least one high-risk (HR)-HPV genotype, and 67.4% by at least one low-risk (LR)-HPV genotype.
- HPV-53, in 27%, was the most prevalent genotype. HPV-6, 11, 16, and 18 prevalence was 22%, 13%, 23%, and 11%, respectively. Of the HR genotypes, HPV-16 and HPV-18 are most often linked with squamous cell cancers and adenocarcinomas, and in the study, prevalence did not change over time.
- Seventy-one percent of participants carried at least one genotype covered by the vaccine, with no change over time.
- On multivariable analysis, the risk of carrying at least one high-risk HPV genotype was linked with younger age (adjusted odds ratio [aOR] for 30 years or younger compared with older than 45 years 2.714; 95% confidence interval [CI], 1.484-4.961), and with having had gonorrhea (aOR, 2.118; 95% CI, 1.100-4.078).
- Also on multivariable analysis, the risk of having one or more genotypes targeted by the 9-valent vaccine was linked with younger age (aOR, 1.868; 95% CI, 1.141-3.060) and with having had gonorrhea (aOR, 1.785; 95% CI, 1.056-3.018).
Mehri S. McKellar, MD, an infectious disease specialist at Duke Health in Durham, N.C., told this news organization.
“This powerful study provides important data on HPV genotype prevalence in the MSM HIV+ population, validating that Gardasil 9 will greatly help these individuals,” said Dr. McKellar, who was not involved in the study.
Robert Salata, MD, infectious disease specialist and professor at Case Western Reserve University, Cleveland, also encourages MSM to get the vaccine.
“It is important to understand that the prevalence of anal HPV in men who have sex with men is very high, that the prevalence, including high-risk genotypes, has remained stable, and that the 9-valent vaccine is clearly indicated, especially in younger men and those with known gonorrhea and other STDs,” Dr. Salata (who was also not involved in the study) told this news organization.
“This is an important reminder for us to continue promoting and providing the vaccine to our patients, especially to HIV+ men who have sex with men, who have the highest rates of anal infection with HPV,” Dr. McKellar advised.
The authors, Dr. McKellar, and Dr. Salata report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Men who have sex with men (MSM) living with HIV, especially those who are young or who’ve had gonorrhea, should get the human papillomavirus (HPV) 9-valent vaccine (Gardasil 9), findings of a newly published study in the Journal of Acquired Immune Deficiency Syndromes suggest.
According to the World Health Organization, only 30% of the target population worldwide has received the HPV vaccine. Despite increased risk for HPV anal infection (an estimated three out of four MSM develop an anal infection from any HPV genotype in their lifetime, epidemiological studies in MSM have been lacking, leaving gaps in data in terms of prevalence rates and prevention.
To help characterize which MSM subgroups benefit the most from early 9-valent HPV vaccination, researchers from Vita-Salute San Raffaele University in Milan determined the prevalence of anal HPV genotypes in MSM who’d been living with HIV for 5 years, and they analyzed the risk factors for HPV anal infection.
Of the 1,352 study participants, 12% were not infected by any HPV genotypes, and the maximum number of genotypes infecting one person (six) was detected in 0.4% (six) people. The prevalence of HR-HPV genotypes or those present in the vaccine remained stable over time.
“Our findings suggest ... that all MSM with HIV would benefit from Gardasil 9 immunization, particularly the youngest and those with a prior gonococcal infection,” wrote Elena Bruzzesi, MD, of Vita-Salute San Raffaele University, and her coauthors.
To determine prevalence of HPV genotypes at anal sites and risk factors, the authors conducted a time-trend, monocentric study on participants who self-identified as MSM who engaged in anal intercourse. The participants underwent one or more anoscopies for HPV genotyping at one academic hospital in Milan between 2015 and 2019.
Swab specimens were collected from the anal canal mucosa, then soaked in thin-layer liquid medium, and sent for molecular analysis.
For detection of HPV phenotypes, the specimens were processed by multiplex real-time polymerase chain reaction.
Findings showed that:
- The overall prevalence of MSM with at least one anal HPV genotype was 88%, with prevalence ranging from 77% to 84%, and no trend difference over the 5-year period.
- Seventy-nine percent of participants were exposed to at least one high-risk (HR)-HPV genotype, and 67.4% by at least one low-risk (LR)-HPV genotype.
- HPV-53, in 27%, was the most prevalent genotype. HPV-6, 11, 16, and 18 prevalence was 22%, 13%, 23%, and 11%, respectively. Of the HR genotypes, HPV-16 and HPV-18 are most often linked with squamous cell cancers and adenocarcinomas, and in the study, prevalence did not change over time.
- Seventy-one percent of participants carried at least one genotype covered by the vaccine, with no change over time.
- On multivariable analysis, the risk of carrying at least one high-risk HPV genotype was linked with younger age (adjusted odds ratio [aOR] for 30 years or younger compared with older than 45 years 2.714; 95% confidence interval [CI], 1.484-4.961), and with having had gonorrhea (aOR, 2.118; 95% CI, 1.100-4.078).
- Also on multivariable analysis, the risk of having one or more genotypes targeted by the 9-valent vaccine was linked with younger age (aOR, 1.868; 95% CI, 1.141-3.060) and with having had gonorrhea (aOR, 1.785; 95% CI, 1.056-3.018).
Mehri S. McKellar, MD, an infectious disease specialist at Duke Health in Durham, N.C., told this news organization.
“This powerful study provides important data on HPV genotype prevalence in the MSM HIV+ population, validating that Gardasil 9 will greatly help these individuals,” said Dr. McKellar, who was not involved in the study.
Robert Salata, MD, infectious disease specialist and professor at Case Western Reserve University, Cleveland, also encourages MSM to get the vaccine.
“It is important to understand that the prevalence of anal HPV in men who have sex with men is very high, that the prevalence, including high-risk genotypes, has remained stable, and that the 9-valent vaccine is clearly indicated, especially in younger men and those with known gonorrhea and other STDs,” Dr. Salata (who was also not involved in the study) told this news organization.
“This is an important reminder for us to continue promoting and providing the vaccine to our patients, especially to HIV+ men who have sex with men, who have the highest rates of anal infection with HPV,” Dr. McKellar advised.
The authors, Dr. McKellar, and Dr. Salata report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Long-acting naltrexone effective in alcohol use disorder
according to findings presented at the annual meeting of the American College of Emergency Physicians.
The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.
“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”
The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.
Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.
The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.
“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”
On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.
Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.
She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.
“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.
Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.
“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”
Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to findings presented at the annual meeting of the American College of Emergency Physicians.
The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.
“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”
The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.
Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.
The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.
“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”
On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.
Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.
She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.
“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.
Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.
“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”
Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to findings presented at the annual meeting of the American College of Emergency Physicians.
The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.
“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”
The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.
Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.
The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.
“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”
On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.
Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.
She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.
“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.
Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.
“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”
Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACEP 2022