News

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

Thousands of health care professionals who separate from active duty each year now have a route to stay in federal health care jobs, including open positions in US Department of Veterans Affairs (VA) hospitals. President Biden signed the Hire Veteran Health Heroes Act of 2021 into law on November 30, saying, “This new program will build upon existing efforts to create a pipeline for former military health professionals….to allow those professionals to continue their service to each other and to our nation.”

Senators Mike Braun (R, Indiana) and Maggie Hassan (D, New Hampshire) introduced the bill last March; Representatives Robert Latta (Ohio-05) and Kathleen Rice (New York-04) introduced companion legislation in the House.

The Act serves multiple purposes, including to retain the critical experience of doctors, nurses, pharmacists, technicians, and physical therapists who understand the challenges service members face; to give those professionals continued employment; and to fill empty staff positions. Two years ago, the VA Inspector General said staff shortages are a root cause of many of the problems in veterans’ care.

 The bill directs the VA to create a program to recruit military medical personnel who are within 1 year of completing their military service. On average, 13,000 active-duty medical department members separate from the military each year at the end of enlistments or contracts, or through retirement. But until now, there has been no formal program to actively recruit them to stay.

The Act requires VA leaders to work with US Department of Defense officials to identify, refer, and transition service members who have critically needed skills. Moreover, the bill specifically mandates that if a member of the Armed Forces expresses an interest in working in a health care occupation within the VA, the VA Secretary “shall refer the member to a recruiter of the Department for consideration of open positions in the specialty and geography of interest to the member.”

Senator Hassan, in an official statement, said, “[W]e must always ensure that veterans have the support and resources that they need to succeed, and a critical way to do that is by expanding employment opportunities for our nation’s heroes and strengthening their health care.”

In his remarks, President Biden said, “For both our veterans and our military medical personnel, service isn’t just what they do, it’s who they are.”

End-of-life discussions happen too late in the treatment of high-risk acute myelogenous leukemia, according to a review of 200 patients at Massachusetts General Hospital and the Dana Farber Cancer Institute, Boston.

The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.

Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.

Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.

Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.

When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.

He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.

Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.

“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”

Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.

As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”

“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.

Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.

Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.

The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.

There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.

aotto@mdedge.com

End-of-life discussions happen too late in the treatment of high-risk acute myelogenous leukemia, according to a review of 200 patients at Massachusetts General Hospital and the Dana Farber Cancer Institute, Boston.

The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.

Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.

Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.

Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.

When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.

He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.

Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.

“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”

Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.

As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”

“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.

Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.

Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.

The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.

There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.

aotto@mdedge.com

End-of-life discussions happen too late in the treatment of high-risk acute myelogenous leukemia, according to a review of 200 patients at Massachusetts General Hospital and the Dana Farber Cancer Institute, Boston.

The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.

Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.

Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.

Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.

When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.

He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.

Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.

“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”

Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.

As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”

“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.

Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.

Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.

The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.

There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.

aotto@mdedge.com

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

One in 10 adults worldwide currently has diabetes, accounting for an estimated global health expenditure of $966 billion in U.S. dollars in 2021, according to the new International Diabetes Federation Diabetes Atlas.

The IDF Atlas, 10th edition, was published online Dec. 6, 2021.

Highlights from it were presented during two sessions at the IDF Virtual Congress 2021, covering global diabetes incidence and prevalence, mortality, and costs, as well as new sections in this edition devoted to adult-onset type 1 diabetes, childhood-onset type 2 diabetes, and the interactions between diabetes and COVID-19.

More detailed data from some of the Atlas chapters were also published Dec. 6, 2021, in separate papers in the IDF journal Diabetes Research and Clinical Practice, with more publications planned.

Information for the Atlas comes from peer-reviewed literature, unpublished reports, and national registries. This latest edition includes 219 data sources from 144 countries, with figures for other countries extrapolated.

Atlas cochair Dianna Magliano, PhD, reviewed some of the highlights. Half of those currently with diabetes, or about 240 million adults, are undiagnosed, and another 319 million have impaired fasting glucose. Over three-quarters of all adults with diabetes now live in low- and middle-income countries. And about 6.7 million deaths in 2021 can be attributed to diabetes.

The Atlas also predicts increases in these numbers over the coming decades if current trends continue.

“Our data and projections tell a sobering story. Diabetes prevalence is expected to increase globally. The number of adults with diabetes will rise from 537 million in 2021 to 786 million ... by the year 2045, an increase of 46%. Rises are expected in every region of the world, with the largest increases expected to occur in the regions of Africa, the Middle East, and Southeast Asia,” said Dr. Magliano, head of diabetes and population health at the Baker Heart and Diabetes Institute, Melbourne.

Since 2019, when the last Atlas was published, the 2021 numbers represent increases of 73.6 million more adults with diabetes including 7.8 million more undiagnosed, 2.5 million more deaths attributed to diabetes, and an additional global expenditure of $206 billion.

Increases have also occurred in the number of people with prediabetes, children with type 1 diabetes, and pregnancies affected by diabetes, Dr. Magliano reported.

“There is a strong need for effective intervention strategies and policies to stall the increase in the number of people developing diabetes across the world,” she added.
 

Projected rise in expenditures for diabetes will be ‘unsustainable’

The current $966 billion global health expenditure caused by diabetes represents a 316% increase from the $232 billion reported in 2006, according to William H. Herman, MD, professor of internal medicine and epidemiology at the University of Michigan, Ann Arbor.

By region, 43% of current diabetes-related global expenditures are in North America, 25% in the Western Pacific, and 20% in Europe, while 12% are from the regions of South and Central America, North Africa, Africa, and Southeast Asia combined, Herman said.

The direct costs of diabetes are projected to grow to $1054 billion in 2045, an increase of just 9% over 25 years. The reason for the far lower increase going forward, compared with the tripling in the 15 years prior, is because of the anticipated diabetes rise in regions of the world where per-person spending on diabetes is low, a situation Dr. Herman called “unsustainable.”

“The keys to controlling the global costs of diabetes care are diabetes prevention and providing effective care to the largest number of people at the lowest possible cost,” he said.
 

Diabetes-related mortality: Some shifts since 2019

One third of the current 6.7 million diabetes-related deaths in 2021 were in people younger than 60 years, said Elbert S. Huang, MD, professor of medicine and public health sciences at the University of Chicago.

Overall, diabetes accounted for 11.8% of total global deaths in people younger than 60 years, but that varied widely, from 24.5% in the Middle East/North Africa to just 6.9% in Southeast Asia.

The regions with the highest number of diabetes-related deaths in people younger than 60 years in 2021 were the Western Pacific and the Middle East/North Africa, a major change from just 2 years ago, when Southeast Asia and Africa saw the greatest numbers of diabetes-related deaths in working-age adults.

“These findings mirror recent reports on inadequate uptake of diabetes prevention programs as well as stagnant quality of care trends for the past decade and reemphasize the need to address noncommunicable diseases across the globe,” Dr. Huang said.
 

Diabetes and COVID-19: Other factors partly explain the increased risk

Gillian Booth, MD, summarized the current literature on COVID-19 and diabetes including a meta-analysis her group conducted of 300 studies from around the world, with 58% from high-income countries.

The risk for increased COVID-19 severity in people with diabetes could be at least partly explained by factors such as age, sex, and comorbidities, said Dr. Booth, professor in the department of medicine and the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

For example, the unadjusted pooled odds of hospitalization with COVID-19 in patients with diabetes, compared with those without diabetes, was 3.69, but dropped to 1.73 after adjustment for age, sex, and having one or more comorbidities. For COVID-19–related death, those odds ratios were 2.32 unadjusted versus 1.59 adjusted. In both cases, the values were still significant after adjustment, she emphasized.

Overall, hyperglycemia and hemoglobin A1c at admission emerged as significant independent predictors of severe outcomes.

“Further research is needed to understand the interplay between COVID-19 and diabetes and how best to address the disproportionate burden of COVID-19 among people living with diabetes,” she stressed.
 

Adult-onset type 1 diabetes: Growing recognition of the burden

Ascertainment of data for both adult-onset type 1 and type 2 diabetes in youth was subject to significant limitations.

For adult-onset type 1 diabetes, Jessica Harding, PhD, pointed to the fact that the epidemiology of adult-onset type 1 diabetes hasn’t been well characterized because of the historical focus on children, the difficulty of distinguishing it from type 2 diabetes in adults, and that many registries simply don’t include incident data across the lifespan for type 1 diabetes.

Nonetheless, she said, “there is growing recognition of the burden of adult-onset type 1,” noting that the American Diabetes Association and European Association for the Study of Diabetes just published a consensus statement addressing the topic.

A systematic review of 46 studies representing 32 countries or regions revealed that countries with the highest incidence of type 1 diabetes onset per population of 100,000 ages 20 or above were Eritrea, at 46.2, followed by Sweden and Ireland, both at 30.6, and Finland, at 0. The lowest rates were in Asian countries.

While the Nordic countries (Finland, Sweden, and Norway) are among the top for incidence of both childhood-onset (0-14 years) and adult-onset type 1 diabetes, Eritrea isn’t even among the top 10 for childhood onset.

The unusual situation in Eritrea is the subject of current study but the reasons aren’t yet clear, noted Dr. Magliano, of Emory University, Atlanta, during the question-and-answer period.

And only seven studies, 15%, used biomarkers to determine type 1 diabetes status, suggesting “there is a pressing need to improve the quality and quantity of information on adult-onset type 1 diabetes, particularly in those low- and middle-income countries,” Dr. Harding said.
 

Type 2 diabetes in youth: A call for better data

When presenting the data for childhood-onset type 2 diabetes, Andrea Luk, MD, noted: “The onset of advanced complications during the most productive time of life has significant impact on individuals, communities, and health economies.”

In 19 studies, the highest reported prevalence of type 2 diabetes in youth was in Brazil, Mexico, indigenous populations of the United States and Canada, and the Black population in the United States, with rates ranging from 160 per 100,000 to 3300 per 100,000. The lowest prevalence rates of 0.6 per 100,000 to 2.7 per 100,000 were reported in Europe. Incidence data were similar, with the highest rates from 31 per 100,000 to 94 per 100,000 and the lowest 0.1 per 100,000 to 0.8 per 100,000 per year.  

Of note, Dr. Luk pointed out that childhood obesity is an important factor but not the only one.

“Some populations that have a low prevalence of obesity, such as East Asians, reported higher incidence rates of youth-onset type 2 diabetes than populations with a greater burden of childhood obesity.”

There was variability in incidence rates for youth of similar ethnic background but from different countries. “Apart from genetic predisposition and background obesogenic environment, disparity in socioeconomic status, access to health care, and cultural practices are other contributors to differences in risk of type 2 diabetes in youth,” noted Dr. Luk, associate professor in the division of endocrinology, Department of Medicine and Therapeutics, Chinese University of Hong Kong.

She also noted that the incidence of type 2 diabetes was extremely low in prepubertal children and rises gradually during puberty, and that the incidence is higher in girls than boys but that reverses in adulthood.

Compared with adults with type 2 diabetes, youth with type 2 diabetes had a more adverse glycemic trajectory and higher rates of metformin failure.

And compared with youth with type 1 diabetes, those with type 2 diabetes had more adverse metabolic profiles and higher rates of vascular complications.

“A strong call must be made for the collection of trend data to assess global burden of type 2 diabetes in youth,” she concluded.

Dr. Luk reported serving as an advisory panel member for and/or receiving research support from Amgen, AstraZeneca, Boehringer Ingelheim, Sanofi, the Asia Diabetes Foundation, Bayer, Lee’s Pharmaceutical, MSD, Novo Nordisk, Roche, Sugardown, and Takeda. The other authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

One in 10 adults worldwide currently has diabetes, accounting for an estimated global health expenditure of $966 billion in U.S. dollars in 2021, according to the new International Diabetes Federation Diabetes Atlas.

The IDF Atlas, 10th edition, was published online Dec. 6, 2021.

Highlights from it were presented during two sessions at the IDF Virtual Congress 2021, covering global diabetes incidence and prevalence, mortality, and costs, as well as new sections in this edition devoted to adult-onset type 1 diabetes, childhood-onset type 2 diabetes, and the interactions between diabetes and COVID-19.

More detailed data from some of the Atlas chapters were also published Dec. 6, 2021, in separate papers in the IDF journal Diabetes Research and Clinical Practice, with more publications planned.

Information for the Atlas comes from peer-reviewed literature, unpublished reports, and national registries. This latest edition includes 219 data sources from 144 countries, with figures for other countries extrapolated.

Atlas cochair Dianna Magliano, PhD, reviewed some of the highlights. Half of those currently with diabetes, or about 240 million adults, are undiagnosed, and another 319 million have impaired fasting glucose. Over three-quarters of all adults with diabetes now live in low- and middle-income countries. And about 6.7 million deaths in 2021 can be attributed to diabetes.

The Atlas also predicts increases in these numbers over the coming decades if current trends continue.

“Our data and projections tell a sobering story. Diabetes prevalence is expected to increase globally. The number of adults with diabetes will rise from 537 million in 2021 to 786 million ... by the year 2045, an increase of 46%. Rises are expected in every region of the world, with the largest increases expected to occur in the regions of Africa, the Middle East, and Southeast Asia,” said Dr. Magliano, head of diabetes and population health at the Baker Heart and Diabetes Institute, Melbourne.

Since 2019, when the last Atlas was published, the 2021 numbers represent increases of 73.6 million more adults with diabetes including 7.8 million more undiagnosed, 2.5 million more deaths attributed to diabetes, and an additional global expenditure of $206 billion.

Increases have also occurred in the number of people with prediabetes, children with type 1 diabetes, and pregnancies affected by diabetes, Dr. Magliano reported.

“There is a strong need for effective intervention strategies and policies to stall the increase in the number of people developing diabetes across the world,” she added.
 

Projected rise in expenditures for diabetes will be ‘unsustainable’

The current $966 billion global health expenditure caused by diabetes represents a 316% increase from the $232 billion reported in 2006, according to William H. Herman, MD, professor of internal medicine and epidemiology at the University of Michigan, Ann Arbor.

By region, 43% of current diabetes-related global expenditures are in North America, 25% in the Western Pacific, and 20% in Europe, while 12% are from the regions of South and Central America, North Africa, Africa, and Southeast Asia combined, Herman said.

The direct costs of diabetes are projected to grow to $1054 billion in 2045, an increase of just 9% over 25 years. The reason for the far lower increase going forward, compared with the tripling in the 15 years prior, is because of the anticipated diabetes rise in regions of the world where per-person spending on diabetes is low, a situation Dr. Herman called “unsustainable.”

“The keys to controlling the global costs of diabetes care are diabetes prevention and providing effective care to the largest number of people at the lowest possible cost,” he said.
 

Diabetes-related mortality: Some shifts since 2019

One third of the current 6.7 million diabetes-related deaths in 2021 were in people younger than 60 years, said Elbert S. Huang, MD, professor of medicine and public health sciences at the University of Chicago.

Overall, diabetes accounted for 11.8% of total global deaths in people younger than 60 years, but that varied widely, from 24.5% in the Middle East/North Africa to just 6.9% in Southeast Asia.

The regions with the highest number of diabetes-related deaths in people younger than 60 years in 2021 were the Western Pacific and the Middle East/North Africa, a major change from just 2 years ago, when Southeast Asia and Africa saw the greatest numbers of diabetes-related deaths in working-age adults.

“These findings mirror recent reports on inadequate uptake of diabetes prevention programs as well as stagnant quality of care trends for the past decade and reemphasize the need to address noncommunicable diseases across the globe,” Dr. Huang said.
 

Diabetes and COVID-19: Other factors partly explain the increased risk

Gillian Booth, MD, summarized the current literature on COVID-19 and diabetes including a meta-analysis her group conducted of 300 studies from around the world, with 58% from high-income countries.

The risk for increased COVID-19 severity in people with diabetes could be at least partly explained by factors such as age, sex, and comorbidities, said Dr. Booth, professor in the department of medicine and the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

For example, the unadjusted pooled odds of hospitalization with COVID-19 in patients with diabetes, compared with those without diabetes, was 3.69, but dropped to 1.73 after adjustment for age, sex, and having one or more comorbidities. For COVID-19–related death, those odds ratios were 2.32 unadjusted versus 1.59 adjusted. In both cases, the values were still significant after adjustment, she emphasized.

Overall, hyperglycemia and hemoglobin A1c at admission emerged as significant independent predictors of severe outcomes.

“Further research is needed to understand the interplay between COVID-19 and diabetes and how best to address the disproportionate burden of COVID-19 among people living with diabetes,” she stressed.
 

Adult-onset type 1 diabetes: Growing recognition of the burden

Ascertainment of data for both adult-onset type 1 and type 2 diabetes in youth was subject to significant limitations.

For adult-onset type 1 diabetes, Jessica Harding, PhD, pointed to the fact that the epidemiology of adult-onset type 1 diabetes hasn’t been well characterized because of the historical focus on children, the difficulty of distinguishing it from type 2 diabetes in adults, and that many registries simply don’t include incident data across the lifespan for type 1 diabetes.

Nonetheless, she said, “there is growing recognition of the burden of adult-onset type 1,” noting that the American Diabetes Association and European Association for the Study of Diabetes just published a consensus statement addressing the topic.

A systematic review of 46 studies representing 32 countries or regions revealed that countries with the highest incidence of type 1 diabetes onset per population of 100,000 ages 20 or above were Eritrea, at 46.2, followed by Sweden and Ireland, both at 30.6, and Finland, at 0. The lowest rates were in Asian countries.

While the Nordic countries (Finland, Sweden, and Norway) are among the top for incidence of both childhood-onset (0-14 years) and adult-onset type 1 diabetes, Eritrea isn’t even among the top 10 for childhood onset.

The unusual situation in Eritrea is the subject of current study but the reasons aren’t yet clear, noted Dr. Magliano, of Emory University, Atlanta, during the question-and-answer period.

And only seven studies, 15%, used biomarkers to determine type 1 diabetes status, suggesting “there is a pressing need to improve the quality and quantity of information on adult-onset type 1 diabetes, particularly in those low- and middle-income countries,” Dr. Harding said.
 

Type 2 diabetes in youth: A call for better data

When presenting the data for childhood-onset type 2 diabetes, Andrea Luk, MD, noted: “The onset of advanced complications during the most productive time of life has significant impact on individuals, communities, and health economies.”

In 19 studies, the highest reported prevalence of type 2 diabetes in youth was in Brazil, Mexico, indigenous populations of the United States and Canada, and the Black population in the United States, with rates ranging from 160 per 100,000 to 3300 per 100,000. The lowest prevalence rates of 0.6 per 100,000 to 2.7 per 100,000 were reported in Europe. Incidence data were similar, with the highest rates from 31 per 100,000 to 94 per 100,000 and the lowest 0.1 per 100,000 to 0.8 per 100,000 per year.  

Of note, Dr. Luk pointed out that childhood obesity is an important factor but not the only one.

“Some populations that have a low prevalence of obesity, such as East Asians, reported higher incidence rates of youth-onset type 2 diabetes than populations with a greater burden of childhood obesity.”

There was variability in incidence rates for youth of similar ethnic background but from different countries. “Apart from genetic predisposition and background obesogenic environment, disparity in socioeconomic status, access to health care, and cultural practices are other contributors to differences in risk of type 2 diabetes in youth,” noted Dr. Luk, associate professor in the division of endocrinology, Department of Medicine and Therapeutics, Chinese University of Hong Kong.

She also noted that the incidence of type 2 diabetes was extremely low in prepubertal children and rises gradually during puberty, and that the incidence is higher in girls than boys but that reverses in adulthood.

Compared with adults with type 2 diabetes, youth with type 2 diabetes had a more adverse glycemic trajectory and higher rates of metformin failure.

And compared with youth with type 1 diabetes, those with type 2 diabetes had more adverse metabolic profiles and higher rates of vascular complications.

“A strong call must be made for the collection of trend data to assess global burden of type 2 diabetes in youth,” she concluded.

Dr. Luk reported serving as an advisory panel member for and/or receiving research support from Amgen, AstraZeneca, Boehringer Ingelheim, Sanofi, the Asia Diabetes Foundation, Bayer, Lee’s Pharmaceutical, MSD, Novo Nordisk, Roche, Sugardown, and Takeda. The other authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

One in 10 adults worldwide currently has diabetes, accounting for an estimated global health expenditure of $966 billion in U.S. dollars in 2021, according to the new International Diabetes Federation Diabetes Atlas.

The IDF Atlas, 10th edition, was published online Dec. 6, 2021.

Highlights from it were presented during two sessions at the IDF Virtual Congress 2021, covering global diabetes incidence and prevalence, mortality, and costs, as well as new sections in this edition devoted to adult-onset type 1 diabetes, childhood-onset type 2 diabetes, and the interactions between diabetes and COVID-19.

More detailed data from some of the Atlas chapters were also published Dec. 6, 2021, in separate papers in the IDF journal Diabetes Research and Clinical Practice, with more publications planned.

Information for the Atlas comes from peer-reviewed literature, unpublished reports, and national registries. This latest edition includes 219 data sources from 144 countries, with figures for other countries extrapolated.

Atlas cochair Dianna Magliano, PhD, reviewed some of the highlights. Half of those currently with diabetes, or about 240 million adults, are undiagnosed, and another 319 million have impaired fasting glucose. Over three-quarters of all adults with diabetes now live in low- and middle-income countries. And about 6.7 million deaths in 2021 can be attributed to diabetes.

The Atlas also predicts increases in these numbers over the coming decades if current trends continue.

“Our data and projections tell a sobering story. Diabetes prevalence is expected to increase globally. The number of adults with diabetes will rise from 537 million in 2021 to 786 million ... by the year 2045, an increase of 46%. Rises are expected in every region of the world, with the largest increases expected to occur in the regions of Africa, the Middle East, and Southeast Asia,” said Dr. Magliano, head of diabetes and population health at the Baker Heart and Diabetes Institute, Melbourne.

Since 2019, when the last Atlas was published, the 2021 numbers represent increases of 73.6 million more adults with diabetes including 7.8 million more undiagnosed, 2.5 million more deaths attributed to diabetes, and an additional global expenditure of $206 billion.

Increases have also occurred in the number of people with prediabetes, children with type 1 diabetes, and pregnancies affected by diabetes, Dr. Magliano reported.

“There is a strong need for effective intervention strategies and policies to stall the increase in the number of people developing diabetes across the world,” she added.
 

Projected rise in expenditures for diabetes will be ‘unsustainable’

The current $966 billion global health expenditure caused by diabetes represents a 316% increase from the $232 billion reported in 2006, according to William H. Herman, MD, professor of internal medicine and epidemiology at the University of Michigan, Ann Arbor.

By region, 43% of current diabetes-related global expenditures are in North America, 25% in the Western Pacific, and 20% in Europe, while 12% are from the regions of South and Central America, North Africa, Africa, and Southeast Asia combined, Herman said.

The direct costs of diabetes are projected to grow to $1054 billion in 2045, an increase of just 9% over 25 years. The reason for the far lower increase going forward, compared with the tripling in the 15 years prior, is because of the anticipated diabetes rise in regions of the world where per-person spending on diabetes is low, a situation Dr. Herman called “unsustainable.”

“The keys to controlling the global costs of diabetes care are diabetes prevention and providing effective care to the largest number of people at the lowest possible cost,” he said.
 

Diabetes-related mortality: Some shifts since 2019

One third of the current 6.7 million diabetes-related deaths in 2021 were in people younger than 60 years, said Elbert S. Huang, MD, professor of medicine and public health sciences at the University of Chicago.

Overall, diabetes accounted for 11.8% of total global deaths in people younger than 60 years, but that varied widely, from 24.5% in the Middle East/North Africa to just 6.9% in Southeast Asia.

The regions with the highest number of diabetes-related deaths in people younger than 60 years in 2021 were the Western Pacific and the Middle East/North Africa, a major change from just 2 years ago, when Southeast Asia and Africa saw the greatest numbers of diabetes-related deaths in working-age adults.

“These findings mirror recent reports on inadequate uptake of diabetes prevention programs as well as stagnant quality of care trends for the past decade and reemphasize the need to address noncommunicable diseases across the globe,” Dr. Huang said.
 

Diabetes and COVID-19: Other factors partly explain the increased risk

Gillian Booth, MD, summarized the current literature on COVID-19 and diabetes including a meta-analysis her group conducted of 300 studies from around the world, with 58% from high-income countries.

The risk for increased COVID-19 severity in people with diabetes could be at least partly explained by factors such as age, sex, and comorbidities, said Dr. Booth, professor in the department of medicine and the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

For example, the unadjusted pooled odds of hospitalization with COVID-19 in patients with diabetes, compared with those without diabetes, was 3.69, but dropped to 1.73 after adjustment for age, sex, and having one or more comorbidities. For COVID-19–related death, those odds ratios were 2.32 unadjusted versus 1.59 adjusted. In both cases, the values were still significant after adjustment, she emphasized.

Overall, hyperglycemia and hemoglobin A1c at admission emerged as significant independent predictors of severe outcomes.

“Further research is needed to understand the interplay between COVID-19 and diabetes and how best to address the disproportionate burden of COVID-19 among people living with diabetes,” she stressed.
 

Adult-onset type 1 diabetes: Growing recognition of the burden

Ascertainment of data for both adult-onset type 1 and type 2 diabetes in youth was subject to significant limitations.

For adult-onset type 1 diabetes, Jessica Harding, PhD, pointed to the fact that the epidemiology of adult-onset type 1 diabetes hasn’t been well characterized because of the historical focus on children, the difficulty of distinguishing it from type 2 diabetes in adults, and that many registries simply don’t include incident data across the lifespan for type 1 diabetes.

Nonetheless, she said, “there is growing recognition of the burden of adult-onset type 1,” noting that the American Diabetes Association and European Association for the Study of Diabetes just published a consensus statement addressing the topic.

A systematic review of 46 studies representing 32 countries or regions revealed that countries with the highest incidence of type 1 diabetes onset per population of 100,000 ages 20 or above were Eritrea, at 46.2, followed by Sweden and Ireland, both at 30.6, and Finland, at 0. The lowest rates were in Asian countries.

While the Nordic countries (Finland, Sweden, and Norway) are among the top for incidence of both childhood-onset (0-14 years) and adult-onset type 1 diabetes, Eritrea isn’t even among the top 10 for childhood onset.

The unusual situation in Eritrea is the subject of current study but the reasons aren’t yet clear, noted Dr. Magliano, of Emory University, Atlanta, during the question-and-answer period.

And only seven studies, 15%, used biomarkers to determine type 1 diabetes status, suggesting “there is a pressing need to improve the quality and quantity of information on adult-onset type 1 diabetes, particularly in those low- and middle-income countries,” Dr. Harding said.
 

Type 2 diabetes in youth: A call for better data

When presenting the data for childhood-onset type 2 diabetes, Andrea Luk, MD, noted: “The onset of advanced complications during the most productive time of life has significant impact on individuals, communities, and health economies.”

In 19 studies, the highest reported prevalence of type 2 diabetes in youth was in Brazil, Mexico, indigenous populations of the United States and Canada, and the Black population in the United States, with rates ranging from 160 per 100,000 to 3300 per 100,000. The lowest prevalence rates of 0.6 per 100,000 to 2.7 per 100,000 were reported in Europe. Incidence data were similar, with the highest rates from 31 per 100,000 to 94 per 100,000 and the lowest 0.1 per 100,000 to 0.8 per 100,000 per year.  

Of note, Dr. Luk pointed out that childhood obesity is an important factor but not the only one.

“Some populations that have a low prevalence of obesity, such as East Asians, reported higher incidence rates of youth-onset type 2 diabetes than populations with a greater burden of childhood obesity.”

There was variability in incidence rates for youth of similar ethnic background but from different countries. “Apart from genetic predisposition and background obesogenic environment, disparity in socioeconomic status, access to health care, and cultural practices are other contributors to differences in risk of type 2 diabetes in youth,” noted Dr. Luk, associate professor in the division of endocrinology, Department of Medicine and Therapeutics, Chinese University of Hong Kong.

She also noted that the incidence of type 2 diabetes was extremely low in prepubertal children and rises gradually during puberty, and that the incidence is higher in girls than boys but that reverses in adulthood.

Compared with adults with type 2 diabetes, youth with type 2 diabetes had a more adverse glycemic trajectory and higher rates of metformin failure.

And compared with youth with type 1 diabetes, those with type 2 diabetes had more adverse metabolic profiles and higher rates of vascular complications.

“A strong call must be made for the collection of trend data to assess global burden of type 2 diabetes in youth,” she concluded.

Dr. Luk reported serving as an advisory panel member for and/or receiving research support from Amgen, AstraZeneca, Boehringer Ingelheim, Sanofi, the Asia Diabetes Foundation, Bayer, Lee’s Pharmaceutical, MSD, Novo Nordisk, Roche, Sugardown, and Takeda. The other authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

A version of this article first appeared on Medscape.com.

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

A version of this article first appeared on Medscape.com.

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

A version of this article first appeared on Medscape.com.

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

A version of this article first appeared on Medscape.com.