User login
ADA issues 2023 ‘Standards of Care’ for diabetes: Focus on tight BP, lipids
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
As COVID treatments dwindle, are new ones waiting in the wings?
It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason:
Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.
Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.
As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?
But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.
Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.
And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
‘A major setback’
The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.
Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.
“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”
Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.
However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.
While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
Antivirals: What’s here, what’s coming
Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.
And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.
Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.
Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.
In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.
The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.
A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.
Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.
Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
Other approaches
A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.
Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.
Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.
So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
Monoclonal antibody treatments?
After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.
“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.
AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”
The AstraZeneca spokesperson said he could share no more information about what the combination would include.
A convalescent plasma comeback?
Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”
With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.
In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
A push for boosters, masks
To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.
In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.
“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.
For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.
Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.
According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.
Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason:
Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.
Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.
As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?
But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.
Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.
And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
‘A major setback’
The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.
Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.
“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”
Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.
However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.
While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
Antivirals: What’s here, what’s coming
Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.
And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.
Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.
Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.
In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.
The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.
A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.
Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.
Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
Other approaches
A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.
Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.
Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.
So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
Monoclonal antibody treatments?
After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.
“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.
AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”
The AstraZeneca spokesperson said he could share no more information about what the combination would include.
A convalescent plasma comeback?
Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”
With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.
In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
A push for boosters, masks
To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.
In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.
“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.
For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.
Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.
According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.
Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason:
Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.
Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.
As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?
But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.
Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.
And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
‘A major setback’
The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.
Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.
“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”
Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.
However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.
While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
Antivirals: What’s here, what’s coming
Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.
And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.
Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.
Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.
In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.
The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.
A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.
Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.
Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
Other approaches
A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.
Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.
Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.
So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
Monoclonal antibody treatments?
After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.
“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.
AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”
The AstraZeneca spokesperson said he could share no more information about what the combination would include.
A convalescent plasma comeback?
Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”
With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.
In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
A push for boosters, masks
To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.
In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.
“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.
For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.
Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.
According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.
Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Does paying people to lose weight work?
It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy.
Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.
The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.
Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.
That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.
A version of this article first appeared on Medscape.com.
It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy.
Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.
The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.
Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.
That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.
A version of this article first appeared on Medscape.com.
It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy.
Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.
The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.
Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.
That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.
A version of this article first appeared on Medscape.com.
Low-carb, high-fat, calorie-unrestricted diet improves type 2 diabetes
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
FROM ANNALS OF INTERNAL MEDICINE
Direct-acting antivirals tied to better outcomes in chronic Hep C
Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.
It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
‘DAA treatment is safe’
“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.
“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.
Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
All-cause mortality reduced by 57%
DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.
The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.
DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
Lower risk of poor nonliver outcomes
The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.
“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.
The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
Large study confirms, introduces DAA benefits
Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.
“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”
Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”
He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”
The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.
Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.
The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.
Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.
It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
‘DAA treatment is safe’
“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.
“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.
Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
All-cause mortality reduced by 57%
DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.
The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.
DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
Lower risk of poor nonliver outcomes
The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.
“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.
The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
Large study confirms, introduces DAA benefits
Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.
“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”
Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”
He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”
The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.
Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.
The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.
Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.
It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
‘DAA treatment is safe’
“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.
“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.
Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
All-cause mortality reduced by 57%
DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.
The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.
DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
Lower risk of poor nonliver outcomes
The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.
“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.
The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
Large study confirms, introduces DAA benefits
Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.
“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”
Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”
He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”
The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.
Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.
The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.
Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
FROM JAMA INTERNAL MEDICINE
Cardiologist sues hospital, claims he was fired in retaliation
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
Three antiseizure medications join list for newborn risks
NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.
In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that
“Because we have this large data set we were able to confirm the suspicion that’s been raised in the past that these drugs may be associated with low birth weight,” Dr. Christensen said in an interview.
The study analyzed records from population-based registers of 4.5 million births in Denmark, Finland, Iceland, Norway, and Sweden between 1996 and 2017, known as the SCAN-AED project. The researchers analyzed the association between prenatal use of antiseizure medications and birth weight, defining low birth weight as less than 5.5 pounds and small for gestational age as being in the lowest 10th percentile for sex, country, and gestational weight at birth.
The antiseizure medications and adjusted odds ratios for risk of low birth rate were:
- Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
- Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
- Topiramate, 1.60 (95% CI, 1.15-2.24).
- Pregabalin, 1.23 (95% CI, 1.02-1.48).
- Clobazam, 4.36 (95% CI, 1.66-11.45).
The odds ratios for being born small for gestational age were:
- Carbamazepine, 1.25 (95% CI, 1.11-1.41).
- Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
- Topiramate, 1.52 (95% CI, 1.20-1.91).
“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.
He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
Use with caution
This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.
“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”
She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.
The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.
NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.
In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that
“Because we have this large data set we were able to confirm the suspicion that’s been raised in the past that these drugs may be associated with low birth weight,” Dr. Christensen said in an interview.
The study analyzed records from population-based registers of 4.5 million births in Denmark, Finland, Iceland, Norway, and Sweden between 1996 and 2017, known as the SCAN-AED project. The researchers analyzed the association between prenatal use of antiseizure medications and birth weight, defining low birth weight as less than 5.5 pounds and small for gestational age as being in the lowest 10th percentile for sex, country, and gestational weight at birth.
The antiseizure medications and adjusted odds ratios for risk of low birth rate were:
- Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
- Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
- Topiramate, 1.60 (95% CI, 1.15-2.24).
- Pregabalin, 1.23 (95% CI, 1.02-1.48).
- Clobazam, 4.36 (95% CI, 1.66-11.45).
The odds ratios for being born small for gestational age were:
- Carbamazepine, 1.25 (95% CI, 1.11-1.41).
- Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
- Topiramate, 1.52 (95% CI, 1.20-1.91).
“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.
He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
Use with caution
This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.
“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”
She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.
The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.
NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.
In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that
“Because we have this large data set we were able to confirm the suspicion that’s been raised in the past that these drugs may be associated with low birth weight,” Dr. Christensen said in an interview.
The study analyzed records from population-based registers of 4.5 million births in Denmark, Finland, Iceland, Norway, and Sweden between 1996 and 2017, known as the SCAN-AED project. The researchers analyzed the association between prenatal use of antiseizure medications and birth weight, defining low birth weight as less than 5.5 pounds and small for gestational age as being in the lowest 10th percentile for sex, country, and gestational weight at birth.
The antiseizure medications and adjusted odds ratios for risk of low birth rate were:
- Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
- Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
- Topiramate, 1.60 (95% CI, 1.15-2.24).
- Pregabalin, 1.23 (95% CI, 1.02-1.48).
- Clobazam, 4.36 (95% CI, 1.66-11.45).
The odds ratios for being born small for gestational age were:
- Carbamazepine, 1.25 (95% CI, 1.11-1.41).
- Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
- Topiramate, 1.52 (95% CI, 1.20-1.91).
“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.
He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
Use with caution
This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.
“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”
She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.
The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.
AT AES 2022
Following the CHEST Foundation in 2022
by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.
Collaboration and communication key in 2022
2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes™ and Bridging Specialties™: Timely Diagnosis for ILD Patients.
A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).
A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.
Plus, a newly launched ILD Clinician Toolkit offers the following and more:
- An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
- A decision-making tool offering interactive simulated patient visits; and
- Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.
Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
The First 5 Minutes
The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.
There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.
Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.
CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
Making medicine a more inclusive practice
In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.
The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).
“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”
Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
Fun and fellowship – for a good cause
In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.
This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.
Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.
Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.
2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.
Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
Twenty-five years of life-changing grants
In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.
by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.
Collaboration and communication key in 2022
2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes™ and Bridging Specialties™: Timely Diagnosis for ILD Patients.
A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).
A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.
Plus, a newly launched ILD Clinician Toolkit offers the following and more:
- An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
- A decision-making tool offering interactive simulated patient visits; and
- Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.
Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
The First 5 Minutes
The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.
There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.
Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.
CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
Making medicine a more inclusive practice
In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.
The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).
“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”
Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
Fun and fellowship – for a good cause
In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.
This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.
Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.
Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.
2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.
Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
Twenty-five years of life-changing grants
In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.
by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.
Collaboration and communication key in 2022
2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes™ and Bridging Specialties™: Timely Diagnosis for ILD Patients.
A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).
A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.
Plus, a newly launched ILD Clinician Toolkit offers the following and more:
- An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
- A decision-making tool offering interactive simulated patient visits; and
- Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.
Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
The First 5 Minutes
The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.
There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.
Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.
CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
Making medicine a more inclusive practice
In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.
The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).
“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”
Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
Fun and fellowship – for a good cause
In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.
This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.
Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.
Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.
2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.
Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
Twenty-five years of life-changing grants
In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.
‘Exciting’ responsiveness to talquetamab for r/r MM
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Pricey gene therapy looks cost-effective for SCD
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022