Federal Practitioner

In Canada, switching to a one-dose, gender-neutral vaccination program for human papillomavirus (HPV) could use vaccine doses more efficiently and prevent a similar number of cervical cancer cases, compared with a two-dose program, according to a new modeling analysis.

If vaccine protection remains high during the ages of peak sexual activity, all one-dose vaccination options are projected to be “substantially more efficient” than two-dose programs, even in the most pessimistic scenarios, the study authors wrote.

In addition, the scenarios projected the elimination of cervical cancer in Canada between 2032 and 2040. HPV can also lead to oral, throat, and penile cancers, and most are preventable through vaccination.

“The COVID-19 pandemic has impacted HPV vaccination in Canada, particularly among vulnerable population subgroups,” said study author Chantal Sauvageau, MD, a consultant in infectious diseases at the National Institute of Public Health of Quebec and associate professor of social and preventive medicine at the University of Laval, Quebec City, Canada.

Switching to one-dose vaccination would offer potential economic savings and programmatic flexibility, she added. The change also could enable investments aimed at increasing vaccination rates in regions where coverage is suboptimal, as well as in subgroups with a high HPV burden. Such initiatives could mitigate the pandemic’s impact on health programs and reduce inequalities.

The study was published online in CMAJ.
 

Vaccination Program Changes

Globally, countries have been investigating whether to shift from a two-dose to a one-dose HPV vaccine strategy since the World Health Organization’s Strategic Advisory Group of Experts on Immunization issued a single-dose recommendation in 2022.

In July, Canada’s National Advisory Committee on Immunization (NACI) updated its guidelines to recommend the single-dose approach for ages 9-20 years. The change aligns Canada with 35 other countries, including Australia and the United Kingdom. Canada›s vaccine advisory group still recommends two doses for ages 21-26 years and three doses for patients who are immunocompromised or have HIV.

To help inform new NACI policies, Sauvageau and colleagues modeled several one-dose and two-dose strategies using HPV-ADVISE, an individual-based transmission-dynamic model of HPV infections and diseases. They looked at vaccination programs in Quebec, which has a high HPV vaccine coverage rate of around 85%, and Ontario, which has lower coverage of around 65%.

For one-dose programs, the researchers analyzed noninferior (98% efficacy) and pessimistic (90% efficacy) scenarios and different average vaccine duration periods, including lifelong, 30-year, and 25-year coverage. They compared the scenarios with a two-dose program with 98% efficacy and lifelong duration, estimating the relative reduction in HPV-16 infection and cervical cancer incidence and the number of doses needed to prevent one cervical cancer case.

Overall, the model projected that gender-neutral HPV vaccine programs with either two doses or a noninferior one dose would nearly eliminate HPV-16 infection by 2040-2045 in Quebec and reduce infection by more than 90% in Ontario. Under a one-dose strategy with 90% vaccine efficacy, rebounds in HPV-16 infection would start more than 25-30 years after a switch to a lower-dose strategy, thus providing time for officials to detect any signs of waning efficacy and change policies, if needed, the authors wrote.

In addition, the model projected that a noninferior one-dose, gender-neutral HPV vaccination program would avert a similar number of cervical cancer cases, compared with a two-dose program. The reduction would be about 60% in Quebec and 55% in Ontario, compared with no vaccination. Under the most pessimistic scenario with 25-year vaccine duration, a one-dose program would be slightly less effective in averting cancer: about 3% lower than a two-dose program over 100 years.

All one-dose scenarios were projected to lead to the elimination of cervical cancer in 8-16 years — at fewer than four cervical cancer cases per 100,000 female-years.

One-dose programs would also lead to more efficient use of vaccine doses, with about 800-1000 doses needed to prevent one cervical cancer case in a one-dose program and more than 10,000 incremental doses needed to prevent one additional cervical cancer case in a two-dose program.
 

What Next?

In Canada, the HPV vaccine is authorized for patients aged 9-45 years. Current immunization coverage among adolescents and young adults varies across provinces and falls below the national target of 90%. In its July 2024 update, NACI estimated that 76% of 14-year-olds of both genders received at least one vaccine dose and that 67% received two doses in 2023. Vaccine uptake was slightly higher among girls than boys.

To boost the coverage rate, shifting to a one-dose schedule could appeal to young people, as well as maintain vaccination efficacy.

“When you look at the studies that have been published worldwide, the effectiveness of one dose of the HPV vaccine is actually quite high,” said Caroline Quach-Thanh, MD, professor of microbiology, infectious diseases, immunology, and pediatrics at the University of Montreal, Quebec, Canada.

Quach-Thanh, who wasn’t involved with this study, previously served as NACI chair and now serves as chair of the Quebec Immunization Committee.

“In terms of prevention of HPV infections that may lead to cancer, whether you give one dose or two doses basically gives you the same amount of protection,” she said.

However, not all physicians agree about the switch in vaccination approaches. In early October, the Federation of Medical Women of Canada released a report with 12 recommendations to increase HPV vaccination rates, including a call for healthcare providers to continue with multidose immunization schedules for now.

“Vaccination is the most powerful action we can take in preventing HPV-related cancers. Canada is falling behind, but we can get back on track if we act quickly,” said Vivien Brown, MD, chair of the group’s HPV Immunization Task Force, chair and cofounder of HPV Prevention Week in Canada, and a past president of the federation.

After the NACI update in July, the task force evaluated the risks and benefits of a single-dose vaccine regimen, she said. They concluded that a multidose schedule should continue at this time because of its proven effectiveness.

“Until more research on the efficacy of a single-dose schedule becomes available, healthcare providers and public health agencies should continue to offer patients a multidose schedule,” said Brown. “This is the only way to ensure individuals are protected against HPV infection and cancer over the long term.”

The study was supported by the Public Health Agency of Canada, the Canadian Institutes of Health Research, the Bill & Melinda Gates Foundation, and Canadian Immunization Research Network. Sauvageau, Quach-Thanh, and Brown declared no relevant financial disclosures.

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

In Canada, switching to a one-dose, gender-neutral vaccination program for human papillomavirus (HPV) could use vaccine doses more efficiently and prevent a similar number of cervical cancer cases, compared with a two-dose program, according to a new modeling analysis.

If vaccine protection remains high during the ages of peak sexual activity, all one-dose vaccination options are projected to be “substantially more efficient” than two-dose programs, even in the most pessimistic scenarios, the study authors wrote.

In addition, the scenarios projected the elimination of cervical cancer in Canada between 2032 and 2040. HPV can also lead to oral, throat, and penile cancers, and most are preventable through vaccination.

“The COVID-19 pandemic has impacted HPV vaccination in Canada, particularly among vulnerable population subgroups,” said study author Chantal Sauvageau, MD, a consultant in infectious diseases at the National Institute of Public Health of Quebec and associate professor of social and preventive medicine at the University of Laval, Quebec City, Canada.

Switching to one-dose vaccination would offer potential economic savings and programmatic flexibility, she added. The change also could enable investments aimed at increasing vaccination rates in regions where coverage is suboptimal, as well as in subgroups with a high HPV burden. Such initiatives could mitigate the pandemic’s impact on health programs and reduce inequalities.

The study was published online in CMAJ.
 

Vaccination Program Changes

Globally, countries have been investigating whether to shift from a two-dose to a one-dose HPV vaccine strategy since the World Health Organization’s Strategic Advisory Group of Experts on Immunization issued a single-dose recommendation in 2022.

In July, Canada’s National Advisory Committee on Immunization (NACI) updated its guidelines to recommend the single-dose approach for ages 9-20 years. The change aligns Canada with 35 other countries, including Australia and the United Kingdom. Canada›s vaccine advisory group still recommends two doses for ages 21-26 years and three doses for patients who are immunocompromised or have HIV.

To help inform new NACI policies, Sauvageau and colleagues modeled several one-dose and two-dose strategies using HPV-ADVISE, an individual-based transmission-dynamic model of HPV infections and diseases. They looked at vaccination programs in Quebec, which has a high HPV vaccine coverage rate of around 85%, and Ontario, which has lower coverage of around 65%.

For one-dose programs, the researchers analyzed noninferior (98% efficacy) and pessimistic (90% efficacy) scenarios and different average vaccine duration periods, including lifelong, 30-year, and 25-year coverage. They compared the scenarios with a two-dose program with 98% efficacy and lifelong duration, estimating the relative reduction in HPV-16 infection and cervical cancer incidence and the number of doses needed to prevent one cervical cancer case.

Overall, the model projected that gender-neutral HPV vaccine programs with either two doses or a noninferior one dose would nearly eliminate HPV-16 infection by 2040-2045 in Quebec and reduce infection by more than 90% in Ontario. Under a one-dose strategy with 90% vaccine efficacy, rebounds in HPV-16 infection would start more than 25-30 years after a switch to a lower-dose strategy, thus providing time for officials to detect any signs of waning efficacy and change policies, if needed, the authors wrote.

In addition, the model projected that a noninferior one-dose, gender-neutral HPV vaccination program would avert a similar number of cervical cancer cases, compared with a two-dose program. The reduction would be about 60% in Quebec and 55% in Ontario, compared with no vaccination. Under the most pessimistic scenario with 25-year vaccine duration, a one-dose program would be slightly less effective in averting cancer: about 3% lower than a two-dose program over 100 years.

All one-dose scenarios were projected to lead to the elimination of cervical cancer in 8-16 years — at fewer than four cervical cancer cases per 100,000 female-years.

One-dose programs would also lead to more efficient use of vaccine doses, with about 800-1000 doses needed to prevent one cervical cancer case in a one-dose program and more than 10,000 incremental doses needed to prevent one additional cervical cancer case in a two-dose program.
 

What Next?

In Canada, the HPV vaccine is authorized for patients aged 9-45 years. Current immunization coverage among adolescents and young adults varies across provinces and falls below the national target of 90%. In its July 2024 update, NACI estimated that 76% of 14-year-olds of both genders received at least one vaccine dose and that 67% received two doses in 2023. Vaccine uptake was slightly higher among girls than boys.

To boost the coverage rate, shifting to a one-dose schedule could appeal to young people, as well as maintain vaccination efficacy.

“When you look at the studies that have been published worldwide, the effectiveness of one dose of the HPV vaccine is actually quite high,” said Caroline Quach-Thanh, MD, professor of microbiology, infectious diseases, immunology, and pediatrics at the University of Montreal, Quebec, Canada.

Quach-Thanh, who wasn’t involved with this study, previously served as NACI chair and now serves as chair of the Quebec Immunization Committee.

“In terms of prevention of HPV infections that may lead to cancer, whether you give one dose or two doses basically gives you the same amount of protection,” she said.

However, not all physicians agree about the switch in vaccination approaches. In early October, the Federation of Medical Women of Canada released a report with 12 recommendations to increase HPV vaccination rates, including a call for healthcare providers to continue with multidose immunization schedules for now.

“Vaccination is the most powerful action we can take in preventing HPV-related cancers. Canada is falling behind, but we can get back on track if we act quickly,” said Vivien Brown, MD, chair of the group’s HPV Immunization Task Force, chair and cofounder of HPV Prevention Week in Canada, and a past president of the federation.

After the NACI update in July, the task force evaluated the risks and benefits of a single-dose vaccine regimen, she said. They concluded that a multidose schedule should continue at this time because of its proven effectiveness.

“Until more research on the efficacy of a single-dose schedule becomes available, healthcare providers and public health agencies should continue to offer patients a multidose schedule,” said Brown. “This is the only way to ensure individuals are protected against HPV infection and cancer over the long term.”

The study was supported by the Public Health Agency of Canada, the Canadian Institutes of Health Research, the Bill & Melinda Gates Foundation, and Canadian Immunization Research Network. Sauvageau, Quach-Thanh, and Brown declared no relevant financial disclosures.

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

In Canada, switching to a one-dose, gender-neutral vaccination program for human papillomavirus (HPV) could use vaccine doses more efficiently and prevent a similar number of cervical cancer cases, compared with a two-dose program, according to a new modeling analysis.

If vaccine protection remains high during the ages of peak sexual activity, all one-dose vaccination options are projected to be “substantially more efficient” than two-dose programs, even in the most pessimistic scenarios, the study authors wrote.

In addition, the scenarios projected the elimination of cervical cancer in Canada between 2032 and 2040. HPV can also lead to oral, throat, and penile cancers, and most are preventable through vaccination.

“The COVID-19 pandemic has impacted HPV vaccination in Canada, particularly among vulnerable population subgroups,” said study author Chantal Sauvageau, MD, a consultant in infectious diseases at the National Institute of Public Health of Quebec and associate professor of social and preventive medicine at the University of Laval, Quebec City, Canada.

Switching to one-dose vaccination would offer potential economic savings and programmatic flexibility, she added. The change also could enable investments aimed at increasing vaccination rates in regions where coverage is suboptimal, as well as in subgroups with a high HPV burden. Such initiatives could mitigate the pandemic’s impact on health programs and reduce inequalities.

The study was published online in CMAJ.
 

Vaccination Program Changes

Globally, countries have been investigating whether to shift from a two-dose to a one-dose HPV vaccine strategy since the World Health Organization’s Strategic Advisory Group of Experts on Immunization issued a single-dose recommendation in 2022.

In July, Canada’s National Advisory Committee on Immunization (NACI) updated its guidelines to recommend the single-dose approach for ages 9-20 years. The change aligns Canada with 35 other countries, including Australia and the United Kingdom. Canada›s vaccine advisory group still recommends two doses for ages 21-26 years and three doses for patients who are immunocompromised or have HIV.

To help inform new NACI policies, Sauvageau and colleagues modeled several one-dose and two-dose strategies using HPV-ADVISE, an individual-based transmission-dynamic model of HPV infections and diseases. They looked at vaccination programs in Quebec, which has a high HPV vaccine coverage rate of around 85%, and Ontario, which has lower coverage of around 65%.

For one-dose programs, the researchers analyzed noninferior (98% efficacy) and pessimistic (90% efficacy) scenarios and different average vaccine duration periods, including lifelong, 30-year, and 25-year coverage. They compared the scenarios with a two-dose program with 98% efficacy and lifelong duration, estimating the relative reduction in HPV-16 infection and cervical cancer incidence and the number of doses needed to prevent one cervical cancer case.

Overall, the model projected that gender-neutral HPV vaccine programs with either two doses or a noninferior one dose would nearly eliminate HPV-16 infection by 2040-2045 in Quebec and reduce infection by more than 90% in Ontario. Under a one-dose strategy with 90% vaccine efficacy, rebounds in HPV-16 infection would start more than 25-30 years after a switch to a lower-dose strategy, thus providing time for officials to detect any signs of waning efficacy and change policies, if needed, the authors wrote.

In addition, the model projected that a noninferior one-dose, gender-neutral HPV vaccination program would avert a similar number of cervical cancer cases, compared with a two-dose program. The reduction would be about 60% in Quebec and 55% in Ontario, compared with no vaccination. Under the most pessimistic scenario with 25-year vaccine duration, a one-dose program would be slightly less effective in averting cancer: about 3% lower than a two-dose program over 100 years.

All one-dose scenarios were projected to lead to the elimination of cervical cancer in 8-16 years — at fewer than four cervical cancer cases per 100,000 female-years.

One-dose programs would also lead to more efficient use of vaccine doses, with about 800-1000 doses needed to prevent one cervical cancer case in a one-dose program and more than 10,000 incremental doses needed to prevent one additional cervical cancer case in a two-dose program.
 

What Next?

In Canada, the HPV vaccine is authorized for patients aged 9-45 years. Current immunization coverage among adolescents and young adults varies across provinces and falls below the national target of 90%. In its July 2024 update, NACI estimated that 76% of 14-year-olds of both genders received at least one vaccine dose and that 67% received two doses in 2023. Vaccine uptake was slightly higher among girls than boys.

To boost the coverage rate, shifting to a one-dose schedule could appeal to young people, as well as maintain vaccination efficacy.

“When you look at the studies that have been published worldwide, the effectiveness of one dose of the HPV vaccine is actually quite high,” said Caroline Quach-Thanh, MD, professor of microbiology, infectious diseases, immunology, and pediatrics at the University of Montreal, Quebec, Canada.

Quach-Thanh, who wasn’t involved with this study, previously served as NACI chair and now serves as chair of the Quebec Immunization Committee.

“In terms of prevention of HPV infections that may lead to cancer, whether you give one dose or two doses basically gives you the same amount of protection,” she said.

However, not all physicians agree about the switch in vaccination approaches. In early October, the Federation of Medical Women of Canada released a report with 12 recommendations to increase HPV vaccination rates, including a call for healthcare providers to continue with multidose immunization schedules for now.

“Vaccination is the most powerful action we can take in preventing HPV-related cancers. Canada is falling behind, but we can get back on track if we act quickly,” said Vivien Brown, MD, chair of the group’s HPV Immunization Task Force, chair and cofounder of HPV Prevention Week in Canada, and a past president of the federation.

After the NACI update in July, the task force evaluated the risks and benefits of a single-dose vaccine regimen, she said. They concluded that a multidose schedule should continue at this time because of its proven effectiveness.

“Until more research on the efficacy of a single-dose schedule becomes available, healthcare providers and public health agencies should continue to offer patients a multidose schedule,” said Brown. “This is the only way to ensure individuals are protected against HPV infection and cancer over the long term.”

The study was supported by the Public Health Agency of Canada, the Canadian Institutes of Health Research, the Bill & Melinda Gates Foundation, and Canadian Immunization Research Network. Sauvageau, Quach-Thanh, and Brown declared no relevant financial disclosures.

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

Primary care doctors and specialists should advise patients who have already experienced a heart attack or stroke that they are at a higher risk for long COVID and need to take steps to avoid contracting the virus, according to new research.

The study, led by researchers at Columbia University, New York City, suggests that anyone with cardiovascular disease (CVD) — defined as having experienced a heart attack or stroke — should consider getting the updated COVID vaccine boosters. They also suggest patients with CVD take other steps to avoid an acute infection, such as avoiding crowded indoor spaces.

There is no specific test or treatment for long COVID, which can become disabling and chronic. Long COVID is defined by the failure to recover from acute COVID-19 in 90 days.

The scientists used data from nearly 5000 people enrolled in 14 established, ongoing research programs, including the 76-year-old Framingham Heart Study. The results of the analysis of the “mega-cohort” were published in JAMA Network Open.

Most of the 14 studies already had 10-20 years of data on the cardiac health of thousands of enrollees, said Norrina B. Allen, one of the authors and a cardiac epidemiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“This is a particularly strong study that looked at risk factors — or individual health — prior to developing COVID and their impact on the likely of recovering from COVID,” she said.

In addition to those with CVD, women and adults with preexisting chronic illnesses took longer to recover.

More than 20% of those in the large, racially and ethnically diverse US population–based study did not recover from COVID in 90 days. The researchers found that the median self-reported time to recovery from acute infection was 20 days.

While women and those with chronic illness had a higher risk for long COVID, vaccination and infection with the Omicron variant wave were associated with shorter recovery times.

These findings make sense, said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University in St. Louis, Missouri.

“We also see that COVID-19 can lead to new-onset cardiovascular disease,” said Al-Aly, who was not involved in the study. “There is clearly a (link) between COVID and cardiovascular disease. These two seem to be intimately intertwined. In my view, this emphasizes the importance of targeting these individuals for vaccination and potentially antivirals (when they get infected) to help reduce their risk of adverse events and ameliorate their chance of full and fast recovery.”

The study used data from the Collaborative Cohort of Cohorts for COVID-19 Research. The long list of researchers contributing to this study includes epidemiologists, biostatisticians, neurologists, pulmonologists, and cardiologists. The data come from a list of cohorts like the Framingham Heart Study, which identified key risk factors for CVD, including cholesterol levels. Other studies include the Atherosclerosis Risk in Communities study, which began in the mid-1980s. Researchers there recruited a cohort of 15,792 men and women in rural North Carolina and Mississippi and suburban Minneapolis. They enrolled a high number of African American participants, who have been underrepresented in past studies. Other cohorts focused on young adults with CVD and Hispanics, while another focused on people with chronic obstructive pulmonary disease.

Lead author Elizabeth C. Oelsner, MD, of Columbia University Irving Medical Center in New York City, said she was not surprised by the CVD-long COVID link.

“We were aware that individuals with CVD were at higher risk of a more severe acute infection,” she said. “We were also seeing evidence that long and severe infection led to persistent symptoms.”

Oelsner noted that many patients still take more than 3 months to recover, even during the Omicron wave.

“While that has improved over the course of the pandemic, many individuals are taking a very long time to recover, and that can have a huge burden on the patient,” she said.

She encourages healthcare providers to tell patients at higher risk to take steps to avoid the virus, including vaccination and boosters.

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

Primary care doctors and specialists should advise patients who have already experienced a heart attack or stroke that they are at a higher risk for long COVID and need to take steps to avoid contracting the virus, according to new research.

The study, led by researchers at Columbia University, New York City, suggests that anyone with cardiovascular disease (CVD) — defined as having experienced a heart attack or stroke — should consider getting the updated COVID vaccine boosters. They also suggest patients with CVD take other steps to avoid an acute infection, such as avoiding crowded indoor spaces.

There is no specific test or treatment for long COVID, which can become disabling and chronic. Long COVID is defined by the failure to recover from acute COVID-19 in 90 days.

The scientists used data from nearly 5000 people enrolled in 14 established, ongoing research programs, including the 76-year-old Framingham Heart Study. The results of the analysis of the “mega-cohort” were published in JAMA Network Open.

Most of the 14 studies already had 10-20 years of data on the cardiac health of thousands of enrollees, said Norrina B. Allen, one of the authors and a cardiac epidemiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“This is a particularly strong study that looked at risk factors — or individual health — prior to developing COVID and their impact on the likely of recovering from COVID,” she said.

In addition to those with CVD, women and adults with preexisting chronic illnesses took longer to recover.

More than 20% of those in the large, racially and ethnically diverse US population–based study did not recover from COVID in 90 days. The researchers found that the median self-reported time to recovery from acute infection was 20 days.

While women and those with chronic illness had a higher risk for long COVID, vaccination and infection with the Omicron variant wave were associated with shorter recovery times.

These findings make sense, said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University in St. Louis, Missouri.

“We also see that COVID-19 can lead to new-onset cardiovascular disease,” said Al-Aly, who was not involved in the study. “There is clearly a (link) between COVID and cardiovascular disease. These two seem to be intimately intertwined. In my view, this emphasizes the importance of targeting these individuals for vaccination and potentially antivirals (when they get infected) to help reduce their risk of adverse events and ameliorate their chance of full and fast recovery.”

The study used data from the Collaborative Cohort of Cohorts for COVID-19 Research. The long list of researchers contributing to this study includes epidemiologists, biostatisticians, neurologists, pulmonologists, and cardiologists. The data come from a list of cohorts like the Framingham Heart Study, which identified key risk factors for CVD, including cholesterol levels. Other studies include the Atherosclerosis Risk in Communities study, which began in the mid-1980s. Researchers there recruited a cohort of 15,792 men and women in rural North Carolina and Mississippi and suburban Minneapolis. They enrolled a high number of African American participants, who have been underrepresented in past studies. Other cohorts focused on young adults with CVD and Hispanics, while another focused on people with chronic obstructive pulmonary disease.

Lead author Elizabeth C. Oelsner, MD, of Columbia University Irving Medical Center in New York City, said she was not surprised by the CVD-long COVID link.

“We were aware that individuals with CVD were at higher risk of a more severe acute infection,” she said. “We were also seeing evidence that long and severe infection led to persistent symptoms.”

Oelsner noted that many patients still take more than 3 months to recover, even during the Omicron wave.

“While that has improved over the course of the pandemic, many individuals are taking a very long time to recover, and that can have a huge burden on the patient,” she said.

She encourages healthcare providers to tell patients at higher risk to take steps to avoid the virus, including vaccination and boosters.

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

Primary care doctors and specialists should advise patients who have already experienced a heart attack or stroke that they are at a higher risk for long COVID and need to take steps to avoid contracting the virus, according to new research.

The study, led by researchers at Columbia University, New York City, suggests that anyone with cardiovascular disease (CVD) — defined as having experienced a heart attack or stroke — should consider getting the updated COVID vaccine boosters. They also suggest patients with CVD take other steps to avoid an acute infection, such as avoiding crowded indoor spaces.

There is no specific test or treatment for long COVID, which can become disabling and chronic. Long COVID is defined by the failure to recover from acute COVID-19 in 90 days.

The scientists used data from nearly 5000 people enrolled in 14 established, ongoing research programs, including the 76-year-old Framingham Heart Study. The results of the analysis of the “mega-cohort” were published in JAMA Network Open.

Most of the 14 studies already had 10-20 years of data on the cardiac health of thousands of enrollees, said Norrina B. Allen, one of the authors and a cardiac epidemiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“This is a particularly strong study that looked at risk factors — or individual health — prior to developing COVID and their impact on the likely of recovering from COVID,” she said.

In addition to those with CVD, women and adults with preexisting chronic illnesses took longer to recover.

More than 20% of those in the large, racially and ethnically diverse US population–based study did not recover from COVID in 90 days. The researchers found that the median self-reported time to recovery from acute infection was 20 days.

While women and those with chronic illness had a higher risk for long COVID, vaccination and infection with the Omicron variant wave were associated with shorter recovery times.

These findings make sense, said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University in St. Louis, Missouri.

“We also see that COVID-19 can lead to new-onset cardiovascular disease,” said Al-Aly, who was not involved in the study. “There is clearly a (link) between COVID and cardiovascular disease. These two seem to be intimately intertwined. In my view, this emphasizes the importance of targeting these individuals for vaccination and potentially antivirals (when they get infected) to help reduce their risk of adverse events and ameliorate their chance of full and fast recovery.”

The study used data from the Collaborative Cohort of Cohorts for COVID-19 Research. The long list of researchers contributing to this study includes epidemiologists, biostatisticians, neurologists, pulmonologists, and cardiologists. The data come from a list of cohorts like the Framingham Heart Study, which identified key risk factors for CVD, including cholesterol levels. Other studies include the Atherosclerosis Risk in Communities study, which began in the mid-1980s. Researchers there recruited a cohort of 15,792 men and women in rural North Carolina and Mississippi and suburban Minneapolis. They enrolled a high number of African American participants, who have been underrepresented in past studies. Other cohorts focused on young adults with CVD and Hispanics, while another focused on people with chronic obstructive pulmonary disease.

Lead author Elizabeth C. Oelsner, MD, of Columbia University Irving Medical Center in New York City, said she was not surprised by the CVD-long COVID link.

“We were aware that individuals with CVD were at higher risk of a more severe acute infection,” she said. “We were also seeing evidence that long and severe infection led to persistent symptoms.”

Oelsner noted that many patients still take more than 3 months to recover, even during the Omicron wave.

“While that has improved over the course of the pandemic, many individuals are taking a very long time to recover, and that can have a huge burden on the patient,” she said.

She encourages healthcare providers to tell patients at higher risk to take steps to avoid the virus, including vaccination and boosters.

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

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

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

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

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

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

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

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A study has found that less than half of US veterans on chronic immunosuppressive medications, and a much lower percentage of those younger than 50 years, received at least one dose of the recombinant zoster vaccine (RZV) by mid-2023; the low rate of herpes zoster vaccination in this immunocompromised group, especially among younger individuals, is concerning.

METHODOLOGY:

• In 2021, the Food and Drug Administration authorized the use of RZV for adults aged 18 years or older on chronic immunosuppressive medications because of their high risk for herpes zoster and its related complications, followed by updated guidance from the Centers for Disease Control and Prevention and American College of Rheumatology in 2021 and 2022, respectively.
• This study aimed to assess the receipt of RZV among veterans receiving immunosuppressive medications within the Veterans Health Administration (VHA) healthcare system before and after the expanded indications in February 2022.
• It included 190,162 veterans who were prescribed one or more immunosuppressive medications for at least 90 days at 130 medical facilities between January 1, 2018, and June 30, 2023.
• A total of 23,295 veterans (12.3%) were younger than 50 years by the end of the study period.
• The outcome measured was the percentage of veterans with one or more doses of RZV documented during the study period.

TAKEAWAY:

• Among veterans aged 50 years or older, 36.2% and 49.8% received an RZV before the expanded indication and by mid-2023, respectively. Even though the rate of vaccination is higher than that observed in the 2021 National Health Interview Survey, significant room for improvement remains.
• Among veterans younger than 50 years, very few (2.8%) received an RZV before the expanded indication, and only 13.4% received it by mid-2023.
• Demographic factors associated with lower odds of vaccination included male sex, African American or unknown race, and nonurban residence (P ≤ .004 for all).
• Those who received targeted synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in combination with other drugs or those who received other vaccines were more likely to receive RZV than those who received conventional synthetic DMARD monotherapy (P < .001 for both).

IN PRACTICE:

“Future work to improve RZV vaccination in patients at high risk should focus on creating informatics tools to identify individuals at high risk and standardizing vaccination guidelines across subspecialties,” the authors wrote.

SOURCE:

This study was led by Sharon Abada, MD, University of California, San Francisco. It was published online on October 11, 2024, in JAMA Network Open.

LIMITATIONS:

This study may not be generalizable to nonveteran populations or countries outside the United States. Limitations also included difficulty with capturing vaccinations not administered within the VHA system, which may have resulted in an underestimation of the percentage of patients vaccinated.

DISCLOSURES:

This work was funded by grants from the VA Quality Enhancement Research Initiative and the Agency for Healthcare Research and Quality. Some authors reported receiving grants from institutions and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Delayed reporting of cancer diagnosis by registries probably led to the weaker-than-expected effects of screening colonoscopy in preventing colorectal cancer (CRC) observed in the NordICC trial, a new analysis found.

METHODOLOGY:

• The NordICC trial randomly assigned 85,179 adults aged 55-64 years in a 1:2 ratio to receive or not receive an invitation for a single screening colonoscopy and determined the risk for CRC diagnosis and death over 10-15 years of follow-up using cancer registries. After randomization, the trial excluded 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization.
• The trial found that CRC risk and associated mortality were lower in adults who had colonoscopy, though only modestly so, which generated considerable controversy.
• Because registration delays are a known concern with population-based cancer registries but the trial did not account for them, researchers on the current study postulated that delays might have led to an underestimation of the impact of colonoscopy on CRC risk.
• They estimated the magnitude of delayed reporting of CRC diagnosis to cancer registries by comparing the 221 exclusions with expected CRC diagnoses per year. They explored the impact that delays may have had on the results of the trial’s intention-to-screen analysis and adjusted per-protocol analysis.

TAKEAWAY:

• The trial’s post hoc exclusion of 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization suggests delays of 2-3 years in registration.
• With no assumed delay in cancer registration, the 10-year reported CRC risk difference was 0.22% in intention-to-screen and 0.38% in adjusted per-protocol analyses. With a mean delay in cancer registration of 2 years, the risk difference rose to 0.44% in the intention-to-screen analysis and 0.76% in the adjusted per-protocol analysis.
• Assuming no delay in cancer registration, the number needed to invite for screening colonoscopy and number needed to undergo the procedure to prevent 1 CRC diagnosis/death were 455 and 263, respectively. These numbers decreased to 227 and 132, respectively, with a 2-year reporting delay.
• Registration delays of 1, 2, or 3 years led to an underestimated risk for CRC by 25%, 50%, and 75%, respectively.

IN PRACTICE:

“Updated analyses ensuring complete 10- and 15-year follow-up will be crucial to derive the true reductions of CRC risk and mortality in the trial’s predefined interim and primary analysis. In the meantime, available estimates are to be interpreted with caution, as they likely severely underestimate true screening colonoscopy effects,” the authors concluded.

The lag in reporting found by the study raises questions about the time interval needed beyond the end of a study to assure its completeness, which varies across registries, wrote Chyke A. Doubeni, MD, MPH, Ohio State University Wexner Medical Center, Columbus, and colleagues in an invited commentary. “Publication guidelines should be strengthened to ensure affirmation of completeness and quality of cancer registries used for outcomes ascertainment to minimize uncertainties.”

SOURCE:

The study, with first author Hermann Brenner, MD, MPH, German Cancer Research Center, Heidelberg, was published online in JAMA Network Open, as was the invited commentary.

LIMITATIONS:

Exact quantification of and correction for registration delays were not possible.

DISCLOSURES:

The study was partially funded by the German Federal Ministry of Education and Research and German Cancer Aid. The authors reported no conflicts of interest.

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

TOPLINE:

Delayed reporting of cancer diagnosis by registries probably led to the weaker-than-expected effects of screening colonoscopy in preventing colorectal cancer (CRC) observed in the NordICC trial, a new analysis found.

METHODOLOGY:

• The NordICC trial randomly assigned 85,179 adults aged 55-64 years in a 1:2 ratio to receive or not receive an invitation for a single screening colonoscopy and determined the risk for CRC diagnosis and death over 10-15 years of follow-up using cancer registries. After randomization, the trial excluded 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization.
• The trial found that CRC risk and associated mortality were lower in adults who had colonoscopy, though only modestly so, which generated considerable controversy.
• Because registration delays are a known concern with population-based cancer registries but the trial did not account for them, researchers on the current study postulated that delays might have led to an underestimation of the impact of colonoscopy on CRC risk.
• They estimated the magnitude of delayed reporting of CRC diagnosis to cancer registries by comparing the 221 exclusions with expected CRC diagnoses per year. They explored the impact that delays may have had on the results of the trial’s intention-to-screen analysis and adjusted per-protocol analysis.

TAKEAWAY:

• The trial’s post hoc exclusion of 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization suggests delays of 2-3 years in registration.
• With no assumed delay in cancer registration, the 10-year reported CRC risk difference was 0.22% in intention-to-screen and 0.38% in adjusted per-protocol analyses. With a mean delay in cancer registration of 2 years, the risk difference rose to 0.44% in the intention-to-screen analysis and 0.76% in the adjusted per-protocol analysis.
• Assuming no delay in cancer registration, the number needed to invite for screening colonoscopy and number needed to undergo the procedure to prevent 1 CRC diagnosis/death were 455 and 263, respectively. These numbers decreased to 227 and 132, respectively, with a 2-year reporting delay.
• Registration delays of 1, 2, or 3 years led to an underestimated risk for CRC by 25%, 50%, and 75%, respectively.

IN PRACTICE:

“Updated analyses ensuring complete 10- and 15-year follow-up will be crucial to derive the true reductions of CRC risk and mortality in the trial’s predefined interim and primary analysis. In the meantime, available estimates are to be interpreted with caution, as they likely severely underestimate true screening colonoscopy effects,” the authors concluded.

The lag in reporting found by the study raises questions about the time interval needed beyond the end of a study to assure its completeness, which varies across registries, wrote Chyke A. Doubeni, MD, MPH, Ohio State University Wexner Medical Center, Columbus, and colleagues in an invited commentary. “Publication guidelines should be strengthened to ensure affirmation of completeness and quality of cancer registries used for outcomes ascertainment to minimize uncertainties.”

SOURCE:

The study, with first author Hermann Brenner, MD, MPH, German Cancer Research Center, Heidelberg, was published online in JAMA Network Open, as was the invited commentary.

LIMITATIONS:

Exact quantification of and correction for registration delays were not possible.

DISCLOSURES:

The study was partially funded by the German Federal Ministry of Education and Research and German Cancer Aid. The authors reported no conflicts of interest.

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

TOPLINE:

Delayed reporting of cancer diagnosis by registries probably led to the weaker-than-expected effects of screening colonoscopy in preventing colorectal cancer (CRC) observed in the NordICC trial, a new analysis found.

METHODOLOGY:

• The NordICC trial randomly assigned 85,179 adults aged 55-64 years in a 1:2 ratio to receive or not receive an invitation for a single screening colonoscopy and determined the risk for CRC diagnosis and death over 10-15 years of follow-up using cancer registries. After randomization, the trial excluded 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization.
• The trial found that CRC risk and associated mortality were lower in adults who had colonoscopy, though only modestly so, which generated considerable controversy.
• Because registration delays are a known concern with population-based cancer registries but the trial did not account for them, researchers on the current study postulated that delays might have led to an underestimation of the impact of colonoscopy on CRC risk.
• They estimated the magnitude of delayed reporting of CRC diagnosis to cancer registries by comparing the 221 exclusions with expected CRC diagnoses per year. They explored the impact that delays may have had on the results of the trial’s intention-to-screen analysis and adjusted per-protocol analysis.

TAKEAWAY:

• The trial’s post hoc exclusion of 221 adults who had CRC at baseline but who did not yet appear in a cancer registry at the time of randomization suggests delays of 2-3 years in registration.
• With no assumed delay in cancer registration, the 10-year reported CRC risk difference was 0.22% in intention-to-screen and 0.38% in adjusted per-protocol analyses. With a mean delay in cancer registration of 2 years, the risk difference rose to 0.44% in the intention-to-screen analysis and 0.76% in the adjusted per-protocol analysis.
• Assuming no delay in cancer registration, the number needed to invite for screening colonoscopy and number needed to undergo the procedure to prevent 1 CRC diagnosis/death were 455 and 263, respectively. These numbers decreased to 227 and 132, respectively, with a 2-year reporting delay.
• Registration delays of 1, 2, or 3 years led to an underestimated risk for CRC by 25%, 50%, and 75%, respectively.

IN PRACTICE:

“Updated analyses ensuring complete 10- and 15-year follow-up will be crucial to derive the true reductions of CRC risk and mortality in the trial’s predefined interim and primary analysis. In the meantime, available estimates are to be interpreted with caution, as they likely severely underestimate true screening colonoscopy effects,” the authors concluded.

The lag in reporting found by the study raises questions about the time interval needed beyond the end of a study to assure its completeness, which varies across registries, wrote Chyke A. Doubeni, MD, MPH, Ohio State University Wexner Medical Center, Columbus, and colleagues in an invited commentary. “Publication guidelines should be strengthened to ensure affirmation of completeness and quality of cancer registries used for outcomes ascertainment to minimize uncertainties.”

SOURCE:

The study, with first author Hermann Brenner, MD, MPH, German Cancer Research Center, Heidelberg, was published online in JAMA Network Open, as was the invited commentary.

LIMITATIONS:

Exact quantification of and correction for registration delays were not possible.

DISCLOSURES:

The study was partially funded by the German Federal Ministry of Education and Research and German Cancer Aid. The authors reported no conflicts of interest.

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

The US Department of Veterans Affairs (VA) will conduct a scientific assessment to find out in whether kidney cancer should be considered a presumptive service-connected condition for veterans exposed to per- and polyfluoroalkyl substances (PFAs). This assessment is the first step in the VA presumptive condition investigative process, which could allow exposed veterans who were exposed to PFAs during their service to access more VA services.

A class of more than 12,000 chemicals, PFAs have been used in the military since the early 1970s in many items, including military-grade firefighting foam. Studies have already suggested links between the so-called forever chemicals and cancer, particularly kidney cancer.

The US Department of Defense (DoD) is assessing contamination at hundreds of sites, while the National Defense Authorization Act in Fiscal Year 2020 mandated that DoD stop using those foams starting in October and remove all stocks from active and former installations and equipment. That may not happen until next year, though, because the DoD has requested a waiver through October 2025 and may extend it through 2026.

When a condition is considered presumptive, eligible veterans do not need to prove their service caused their disease to receive benefits. As part of the Biden Administration’s efforts to expand benefits and services for toxin-exposed veterans and their families, the VA expedited health care and benefits eligibility under the PACT Act by several years—including extending presumptions for head cancer, neck cancer, gastrointestinal cancer, reproductive cancer, lymphoma, pancreatic cancer, kidney cancer, melanoma, and hypertension for Vietnam era veterans. The VA has also extended presumptions for > 300 new conditions, most recently for male breast cancer, urethral cancer, and cancer of the paraurethral glands.

Whether a condition is an established presumptive condition or not, the VA will consider claims on a case-by-case basis and can grant disability compensation benefits if sufficient evidence of service connection is found. “[M]ake no mistake: Veterans should not wait for the outcome of this review to apply for the benefits and care they deserve,” VA Secretary Denis McDonough said in a release.  “If you’re a veteran and believe your military service has negatively impacted your health, we encourage you to apply for VA care and benefits today.”

The public has 30 days to comment on the proposed scientific assessment between PFAs exposure and kidney cancer via the Federal Register. The VA is set to host a listening session on Nov. 19, 2024, to allow individuals to share research and input. Interested individuals may register to participate. The public may also comment via either forum on other conditions that would benefit from review for potential service-connection.

The US Department of Veterans Affairs (VA) will conduct a scientific assessment to find out in whether kidney cancer should be considered a presumptive service-connected condition for veterans exposed to per- and polyfluoroalkyl substances (PFAs). This assessment is the first step in the VA presumptive condition investigative process, which could allow exposed veterans who were exposed to PFAs during their service to access more VA services.

A class of more than 12,000 chemicals, PFAs have been used in the military since the early 1970s in many items, including military-grade firefighting foam. Studies have already suggested links between the so-called forever chemicals and cancer, particularly kidney cancer.

The US Department of Defense (DoD) is assessing contamination at hundreds of sites, while the National Defense Authorization Act in Fiscal Year 2020 mandated that DoD stop using those foams starting in October and remove all stocks from active and former installations and equipment. That may not happen until next year, though, because the DoD has requested a waiver through October 2025 and may extend it through 2026.

When a condition is considered presumptive, eligible veterans do not need to prove their service caused their disease to receive benefits. As part of the Biden Administration’s efforts to expand benefits and services for toxin-exposed veterans and their families, the VA expedited health care and benefits eligibility under the PACT Act by several years—including extending presumptions for head cancer, neck cancer, gastrointestinal cancer, reproductive cancer, lymphoma, pancreatic cancer, kidney cancer, melanoma, and hypertension for Vietnam era veterans. The VA has also extended presumptions for > 300 new conditions, most recently for male breast cancer, urethral cancer, and cancer of the paraurethral glands.

Whether a condition is an established presumptive condition or not, the VA will consider claims on a case-by-case basis and can grant disability compensation benefits if sufficient evidence of service connection is found. “[M]ake no mistake: Veterans should not wait for the outcome of this review to apply for the benefits and care they deserve,” VA Secretary Denis McDonough said in a release.  “If you’re a veteran and believe your military service has negatively impacted your health, we encourage you to apply for VA care and benefits today.”

The public has 30 days to comment on the proposed scientific assessment between PFAs exposure and kidney cancer via the Federal Register. The VA is set to host a listening session on Nov. 19, 2024, to allow individuals to share research and input. Interested individuals may register to participate. The public may also comment via either forum on other conditions that would benefit from review for potential service-connection.

The US Department of Veterans Affairs (VA) will conduct a scientific assessment to find out in whether kidney cancer should be considered a presumptive service-connected condition for veterans exposed to per- and polyfluoroalkyl substances (PFAs). This assessment is the first step in the VA presumptive condition investigative process, which could allow exposed veterans who were exposed to PFAs during their service to access more VA services.

A class of more than 12,000 chemicals, PFAs have been used in the military since the early 1970s in many items, including military-grade firefighting foam. Studies have already suggested links between the so-called forever chemicals and cancer, particularly kidney cancer.

The US Department of Defense (DoD) is assessing contamination at hundreds of sites, while the National Defense Authorization Act in Fiscal Year 2020 mandated that DoD stop using those foams starting in October and remove all stocks from active and former installations and equipment. That may not happen until next year, though, because the DoD has requested a waiver through October 2025 and may extend it through 2026.

When a condition is considered presumptive, eligible veterans do not need to prove their service caused their disease to receive benefits. As part of the Biden Administration’s efforts to expand benefits and services for toxin-exposed veterans and their families, the VA expedited health care and benefits eligibility under the PACT Act by several years—including extending presumptions for head cancer, neck cancer, gastrointestinal cancer, reproductive cancer, lymphoma, pancreatic cancer, kidney cancer, melanoma, and hypertension for Vietnam era veterans. The VA has also extended presumptions for > 300 new conditions, most recently for male breast cancer, urethral cancer, and cancer of the paraurethral glands.

Whether a condition is an established presumptive condition or not, the VA will consider claims on a case-by-case basis and can grant disability compensation benefits if sufficient evidence of service connection is found. “[M]ake no mistake: Veterans should not wait for the outcome of this review to apply for the benefits and care they deserve,” VA Secretary Denis McDonough said in a release.  “If you’re a veteran and believe your military service has negatively impacted your health, we encourage you to apply for VA care and benefits today.”

The public has 30 days to comment on the proposed scientific assessment between PFAs exposure and kidney cancer via the Federal Register. The VA is set to host a listening session on Nov. 19, 2024, to allow individuals to share research and input. Interested individuals may register to participate. The public may also comment via either forum on other conditions that would benefit from review for potential service-connection.

The US Department of Veterans Affairs (VA) has announced that tele-emergency care (tele-EC) is now available nationwide. According to the VA, the expansion has already helped > 61,000 callers with a 59.4% case resolution rate, meaning veterans’ needs were resolved without them having to travel to urgent care or an emergency department.

Tele-EC does not replace the need for in-person emergency evaluation, but offers quick, virtual triage assessments for veterans in rural areas or those with mobility and transportation challenges when in-person immediate care can be difficult to access. The program is a part of VA Health Connect, which connects the caller to a clinical triage nurse, who connects the veteran to tele-emergency care when clinically appropriate. Tele-EC practitioners evaluate the veteran over the phone or on video and recommend treatment or follow-up, including in-person care if needed. In life-threatening emergencies, the clinical triage nurse will call 911 and stay on the phone with the veteran until help arrives. The VA however, says the best step for a veteran experiencing a life-threatening emergency is to immediately contact 911 as opposed to seeking support via tele-EC.

The program can save time not only through on-the-spot evaluation, but by avoiding drive and wait times. “Sometimes, you’re not sure whether what you’re experiencing is a minor emergency or not — and tele-emergency care can help you resolve those questions,” VA Under Secretary for Health Shereef Elnahal, MD, says. “Veterans can get immediate, virtual triage with a VA medical provider who has direct access to their medical records. This avoids having to potentially drive to the nearest emergency department and wait to be evaluated, if appropriate.”

Veterans enrolled in VA health care can now access tele-EC nationwide by calling VA Health Connect and through the VA Health Chat app. Veterans can find their local VA Health Connect number by searching for their facility.

The US Department of Veterans Affairs (VA) has announced that tele-emergency care (tele-EC) is now available nationwide. According to the VA, the expansion has already helped > 61,000 callers with a 59.4% case resolution rate, meaning veterans’ needs were resolved without them having to travel to urgent care or an emergency department.

Tele-EC does not replace the need for in-person emergency evaluation, but offers quick, virtual triage assessments for veterans in rural areas or those with mobility and transportation challenges when in-person immediate care can be difficult to access. The program is a part of VA Health Connect, which connects the caller to a clinical triage nurse, who connects the veteran to tele-emergency care when clinically appropriate. Tele-EC practitioners evaluate the veteran over the phone or on video and recommend treatment or follow-up, including in-person care if needed. In life-threatening emergencies, the clinical triage nurse will call 911 and stay on the phone with the veteran until help arrives. The VA however, says the best step for a veteran experiencing a life-threatening emergency is to immediately contact 911 as opposed to seeking support via tele-EC.

The program can save time not only through on-the-spot evaluation, but by avoiding drive and wait times. “Sometimes, you’re not sure whether what you’re experiencing is a minor emergency or not — and tele-emergency care can help you resolve those questions,” VA Under Secretary for Health Shereef Elnahal, MD, says. “Veterans can get immediate, virtual triage with a VA medical provider who has direct access to their medical records. This avoids having to potentially drive to the nearest emergency department and wait to be evaluated, if appropriate.”

Veterans enrolled in VA health care can now access tele-EC nationwide by calling VA Health Connect and through the VA Health Chat app. Veterans can find their local VA Health Connect number by searching for their facility.

The US Department of Veterans Affairs (VA) has announced that tele-emergency care (tele-EC) is now available nationwide. According to the VA, the expansion has already helped > 61,000 callers with a 59.4% case resolution rate, meaning veterans’ needs were resolved without them having to travel to urgent care or an emergency department.

Tele-EC does not replace the need for in-person emergency evaluation, but offers quick, virtual triage assessments for veterans in rural areas or those with mobility and transportation challenges when in-person immediate care can be difficult to access. The program is a part of VA Health Connect, which connects the caller to a clinical triage nurse, who connects the veteran to tele-emergency care when clinically appropriate. Tele-EC practitioners evaluate the veteran over the phone or on video and recommend treatment or follow-up, including in-person care if needed. In life-threatening emergencies, the clinical triage nurse will call 911 and stay on the phone with the veteran until help arrives. The VA however, says the best step for a veteran experiencing a life-threatening emergency is to immediately contact 911 as opposed to seeking support via tele-EC.

The program can save time not only through on-the-spot evaluation, but by avoiding drive and wait times. “Sometimes, you’re not sure whether what you’re experiencing is a minor emergency or not — and tele-emergency care can help you resolve those questions,” VA Under Secretary for Health Shereef Elnahal, MD, says. “Veterans can get immediate, virtual triage with a VA medical provider who has direct access to their medical records. This avoids having to potentially drive to the nearest emergency department and wait to be evaluated, if appropriate.”

Veterans enrolled in VA health care can now access tele-EC nationwide by calling VA Health Connect and through the VA Health Chat app. Veterans can find their local VA Health Connect number by searching for their facility.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Testing for mismatch repair (MMR) and microsatellite instability (MSI) among patients with colorectal cancer (CRC) increased from 22.7% in 2012 to 71.5% in 2021, but variations in access remain, with testing rates differing by cancer stage, individual hospital, patient sex, race, and insurance status.

METHODOLOGY:

• In 2017, the National Comprehensive Cancer Network (NCCN) recommended universal testing for MMR and MSI among patients with CRC, but studies suggest that testing may still be underused.
• To assess trends and factors associated with MMR/MSI testing in the United States, researchers evaluated 834,797 patients diagnosed with stage I-IV CRC between 2012 and 2021 across 1366 Commission on Cancer–accredited hospitals in the National Cancer Database.
• The variability in MMR/MSI testing was assessed in relation to both patient and hospital-level factors.
• Overall, 70.7% patients had colon cancer, 7.3% had rectosigmoid cancer, and 22.0% had rectal cancer. The median patient age was 66 years; just over half (53%) were men, 81.8% were White, and 11.9% were Black.

TAKEAWAY:

• Overall, 43.9% patients underwent MMR/MSI testing, but testing rates increased more than threefold between 2012 and 2021 — from 22.7% to 71.5%. Still, testing rates varied depending on a range of factors.
• About 22% variability in MMR/MSI testing was attributed to hospital-level variations, with the best vs worst performing hospitals reporting testing rates of 90% vs 2%. This hospital-level variation may be caused by testing protocol differences at individual institutions, the authors said.
• The likelihood of undergoing MMR/MSI testing was lower in patients with stage IV vs stage I disease (adjusted odds ratio [aOR], 0.78) but higher in those with stage II (aOR, 1.53) and III (aOR, 1.40) disease.
• The likelihood of undergoing MMR/MSI testing was slightly lower for men than for women (aOR, 0.98) and for Black patients than for White patients (aOR, 0.97). Having a lower household income, public or no insurance (vs private insurance), or living a longer distance (more than 5 miles) from the treatment facility was also associated with lower odds of testing.

IN PRACTICE:

“This cohort study indicated that MMR/MSI testing increased markedly, suggesting increased NCCN guideline adherence,” the authors said. However, variations still exist by cancer stage, hospital, and patient factors. Implementing “widespread institution-level reflexive testing for every initial diagnostic biopsy” can improve testing rates and reduce disparities, the authors suggested.

SOURCE:

This study, led by Totadri Dhimal, MD, University of Rochester Medical Center in New York, was published online in JAMA Oncology.

LIMITATIONS:

The study lacked clinical granularity, and potential coding inaccuracies and incomplete data could have affected the interpretation and generalizability of the findings.

DISCLOSURES:

No funding information was provided for the study. One author reported receiving author royalties from UpToDate outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

This transcript has been edited for clarity. 

Welcome back, everybody, from the European Society for Medical Oncology (ESMO) Congress in the wonderful city of Barcelona in Spain. I was coming from ESMO drenched in huge amounts of new data. 

One of the things I picked up on was a nice mini-symposium on gastrointestinal cancer led by Sara Lonardi, who made an excellent presentation, picking out three abstracts. They looked at molecularly targeted drugs, some early-stage and a later-stage study in which there’s some evidence of promise.

She talked a little about the preliminary results from three trials suggesting some benefits, pretty marginal, of cetuximab plus irinotecan in patients who’d already had epidermal growth factor receptor (EGFR) receptor inhibitory treatment. 

Amivantamab plus FOLFOX or FOLFIRI was also discussed. This is a bispecific antibody against EGFR and MET. Again, very early, but there are some potential marginal benefits coming through. She also discussed the results of a larger phase 3 randomized trial with an old friend, ramucirumab, the anti-angiogenic agent, in which the ramucirumab in combination with trifluridine-tipiracil failed to meet its primary endpoint of improving overall survival.

There were some interesting post hoc subgroup analyses showing potential benefits for women, left-sided tumors, and so on. She made an excellent presentation, which she summarized by saying that the future of colorectal cancer treatment lies in further defining molecularly targeted treatment.

Nobody would disagree with that. What is interesting, though, is that, if I were to use the analogy of mining, the more deeply we mine, perhaps the lower marginal the benefits are becoming. There’s no doubt that we’re understanding better the exquisite machinery of cell signaling. We understand that there’s redundancy, there’s repeatability, and the possibility of emergence of resistance can come quite quickly. 

Although we can develop ever more precise molecularly targeted drugs, it does seem as if the clinical benefits of these, in some cases, are marginally small. I’d like to suggest that, in addition to Sara’s call for more molecularly targeted drugs, we should think about cellular targets. 

We did a large amount of work (as have many others, of course) looking at the immune tumor microenvironment and trying to, in a way, separate and understand the contribution of the individual component cells — of which there are many, including cancer-associated fibroblasts, natural killer (NK) cells, whole hosts of different types of T-cell subsets, B cells, tumor-associated neutrophils, and so on — and how these interact together and of interact with the epithelial colorectal cancer cells. 

We are collaborating with Patrick Soon-Shiong, a clever chap, who believes in combination immunotherapy, dissecting and understanding the individual role of these different cells, and coming up with cellular therapies or targeted therapies that either inhibit or stimulate some of the different cell components to be the way ahead for an immunologically cold tumor such as microsatellite-stable colorectal cancer.

For example, we’re looking at combinations of our histone deacetylase (HDAC) inhibitor, which switches on the machinery of antigen presentation, up-regulating major histocompatibility complex (MHC) class 1 and class 2, and some other of the molecules involved in antigen chopping and presentation; it’s like turning a microsatellite-stable immunologically cold tumor hot; an interleukin-15 superagonist that stimulates NK cells; and we’ve found a way to manipulate and reduce the number of Treg cells. 

We have various approaches to reducing the microenvironment transforming growth factor beta and some of the downstream elements from that. We can look at combinatorial immunotherapy, but thinking at a cellular level and developing anticancer agents that either activate or inhibit these different cell components. I’d bring the two together. 

Of course, the future has got to be better molecularly targeted drugs, but let’s think at a macro level as to how we can look at the different cellular interactions within the tumor microenvironment, and perhaps through that, come up with synergistic immunotherapeutic combinations.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, and Professor of Cancer Medicine, Oxford Cancer Centre, both in England. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Genomic Health, and Merck Serono.

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

This transcript has been edited for clarity. 

Welcome back, everybody, from the European Society for Medical Oncology (ESMO) Congress in the wonderful city of Barcelona in Spain. I was coming from ESMO drenched in huge amounts of new data. 

One of the things I picked up on was a nice mini-symposium on gastrointestinal cancer led by Sara Lonardi, who made an excellent presentation, picking out three abstracts. They looked at molecularly targeted drugs, some early-stage and a later-stage study in which there’s some evidence of promise.

She talked a little about the preliminary results from three trials suggesting some benefits, pretty marginal, of cetuximab plus irinotecan in patients who’d already had epidermal growth factor receptor (EGFR) receptor inhibitory treatment. 

Amivantamab plus FOLFOX or FOLFIRI was also discussed. This is a bispecific antibody against EGFR and MET. Again, very early, but there are some potential marginal benefits coming through. She also discussed the results of a larger phase 3 randomized trial with an old friend, ramucirumab, the anti-angiogenic agent, in which the ramucirumab in combination with trifluridine-tipiracil failed to meet its primary endpoint of improving overall survival.

There were some interesting post hoc subgroup analyses showing potential benefits for women, left-sided tumors, and so on. She made an excellent presentation, which she summarized by saying that the future of colorectal cancer treatment lies in further defining molecularly targeted treatment.

Nobody would disagree with that. What is interesting, though, is that, if I were to use the analogy of mining, the more deeply we mine, perhaps the lower marginal the benefits are becoming. There’s no doubt that we’re understanding better the exquisite machinery of cell signaling. We understand that there’s redundancy, there’s repeatability, and the possibility of emergence of resistance can come quite quickly. 

Although we can develop ever more precise molecularly targeted drugs, it does seem as if the clinical benefits of these, in some cases, are marginally small. I’d like to suggest that, in addition to Sara’s call for more molecularly targeted drugs, we should think about cellular targets. 

We did a large amount of work (as have many others, of course) looking at the immune tumor microenvironment and trying to, in a way, separate and understand the contribution of the individual component cells — of which there are many, including cancer-associated fibroblasts, natural killer (NK) cells, whole hosts of different types of T-cell subsets, B cells, tumor-associated neutrophils, and so on — and how these interact together and of interact with the epithelial colorectal cancer cells. 

We are collaborating with Patrick Soon-Shiong, a clever chap, who believes in combination immunotherapy, dissecting and understanding the individual role of these different cells, and coming up with cellular therapies or targeted therapies that either inhibit or stimulate some of the different cell components to be the way ahead for an immunologically cold tumor such as microsatellite-stable colorectal cancer.

For example, we’re looking at combinations of our histone deacetylase (HDAC) inhibitor, which switches on the machinery of antigen presentation, up-regulating major histocompatibility complex (MHC) class 1 and class 2, and some other of the molecules involved in antigen chopping and presentation; it’s like turning a microsatellite-stable immunologically cold tumor hot; an interleukin-15 superagonist that stimulates NK cells; and we’ve found a way to manipulate and reduce the number of Treg cells. 

We have various approaches to reducing the microenvironment transforming growth factor beta and some of the downstream elements from that. We can look at combinatorial immunotherapy, but thinking at a cellular level and developing anticancer agents that either activate or inhibit these different cell components. I’d bring the two together. 

Of course, the future has got to be better molecularly targeted drugs, but let’s think at a macro level as to how we can look at the different cellular interactions within the tumor microenvironment, and perhaps through that, come up with synergistic immunotherapeutic combinations.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, and Professor of Cancer Medicine, Oxford Cancer Centre, both in England. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Genomic Health, and Merck Serono.

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

This transcript has been edited for clarity. 

Welcome back, everybody, from the European Society for Medical Oncology (ESMO) Congress in the wonderful city of Barcelona in Spain. I was coming from ESMO drenched in huge amounts of new data. 

One of the things I picked up on was a nice mini-symposium on gastrointestinal cancer led by Sara Lonardi, who made an excellent presentation, picking out three abstracts. They looked at molecularly targeted drugs, some early-stage and a later-stage study in which there’s some evidence of promise.

She talked a little about the preliminary results from three trials suggesting some benefits, pretty marginal, of cetuximab plus irinotecan in patients who’d already had epidermal growth factor receptor (EGFR) receptor inhibitory treatment. 

Amivantamab plus FOLFOX or FOLFIRI was also discussed. This is a bispecific antibody against EGFR and MET. Again, very early, but there are some potential marginal benefits coming through. She also discussed the results of a larger phase 3 randomized trial with an old friend, ramucirumab, the anti-angiogenic agent, in which the ramucirumab in combination with trifluridine-tipiracil failed to meet its primary endpoint of improving overall survival.

There were some interesting post hoc subgroup analyses showing potential benefits for women, left-sided tumors, and so on. She made an excellent presentation, which she summarized by saying that the future of colorectal cancer treatment lies in further defining molecularly targeted treatment.

Nobody would disagree with that. What is interesting, though, is that, if I were to use the analogy of mining, the more deeply we mine, perhaps the lower marginal the benefits are becoming. There’s no doubt that we’re understanding better the exquisite machinery of cell signaling. We understand that there’s redundancy, there’s repeatability, and the possibility of emergence of resistance can come quite quickly. 

Although we can develop ever more precise molecularly targeted drugs, it does seem as if the clinical benefits of these, in some cases, are marginally small. I’d like to suggest that, in addition to Sara’s call for more molecularly targeted drugs, we should think about cellular targets. 

We did a large amount of work (as have many others, of course) looking at the immune tumor microenvironment and trying to, in a way, separate and understand the contribution of the individual component cells — of which there are many, including cancer-associated fibroblasts, natural killer (NK) cells, whole hosts of different types of T-cell subsets, B cells, tumor-associated neutrophils, and so on — and how these interact together and of interact with the epithelial colorectal cancer cells. 

We are collaborating with Patrick Soon-Shiong, a clever chap, who believes in combination immunotherapy, dissecting and understanding the individual role of these different cells, and coming up with cellular therapies or targeted therapies that either inhibit or stimulate some of the different cell components to be the way ahead for an immunologically cold tumor such as microsatellite-stable colorectal cancer.

For example, we’re looking at combinations of our histone deacetylase (HDAC) inhibitor, which switches on the machinery of antigen presentation, up-regulating major histocompatibility complex (MHC) class 1 and class 2, and some other of the molecules involved in antigen chopping and presentation; it’s like turning a microsatellite-stable immunologically cold tumor hot; an interleukin-15 superagonist that stimulates NK cells; and we’ve found a way to manipulate and reduce the number of Treg cells. 

We have various approaches to reducing the microenvironment transforming growth factor beta and some of the downstream elements from that. We can look at combinatorial immunotherapy, but thinking at a cellular level and developing anticancer agents that either activate or inhibit these different cell components. I’d bring the two together. 

Of course, the future has got to be better molecularly targeted drugs, but let’s think at a macro level as to how we can look at the different cellular interactions within the tumor microenvironment, and perhaps through that, come up with synergistic immunotherapeutic combinations.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, and Professor of Cancer Medicine, Oxford Cancer Centre, both in England. He reported conflicts of interest with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Genomic Health, and Merck Serono.

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