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‘Striking’ differences in BP when wrong cuff size is used
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).
The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.
However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.
The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).
“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”
She noted, for example, that people who required an extra-large cuff and were measured with a regular cuff had an average BP of 144/86.7 mm Hg, which is in the stage 2 hypertension range. But when the correct size cuff was used, the average BP was 124.5/79.3 mm Hg, or in the prehypertensive range.
Overall, the overestimation of BP due to using too small a cuff misclassified 39% of people as being hypertensive, while the underestimation of BP due to using a cuff that was too large missed 22% of people with hypertension.
“So, I think clinicians really need to have a renewed emphasis on cuff size, especially in populations where obesity is highly prevalent and many of their patients require extra-large cuffs, because those are the populations that are most impacted by mis-cuffing,” Dr. Brady said.
The findings were presented in an E-poster at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health (EPI/Lifestyle) 2022 conference sponsored by the American Heart Association.
Willie Lawrence, MD, chair of the AHA’s National Hypertension Control Initiative Advisory Committee, said in an interview that the magnitude of inaccuracy observed by the researchers “makes this a very, very important study.”
“Is it the first of its kind, no, but it’s incredibly important because it was so well done, and it comes at a time when people are once again dealing with issues around equity, and this study can have a significant impact on the state of hypertension in diverse communities,” said Dr. Lawrence, a cardiologist with Spectrum Health Lakeland, Benton Harbor, Michigan.
Previous studies examining the issue were older, had few participants, and used mercury sphygmomanometers instead of automated devices, which are typically recommended by professional societies for screening hypertension in adults, Dr. Brady explained.
For the Cuff Size Blood Pressure Measurement trial, 195 adults recruited from the community underwent 2 to 3 sets of 3 BP readings, 30 seconds apart, with an automated and validated device (Welch Allyn ProB 2000) using a BP cuff that was appropriated sized, one size lower, and one size higher. The order of cuff sizes was randomized. Before each set, patients walked for 2 minutes, followed by 5 minutes of rest to eliminate the potential effect of longer resting periods between tests on the results. The room was also kept quiet and participants were asked not to speak or use a smart phone.
Participants had a mean age of 54 years, 34% were male, 68% were Black, and 36% had a body mass index of at least 30 kg/m2, meeting the criteria for obesity.
Roughly one-half had a self-reported hypertension diagnosis, 31% had a systolic BP of 130 mm Hg or greater, and 26% had a diastolic BP of 80 mm Hg or greater.
Based on arm circumference (mean, 34 cm), the appropriate adult cuff size was small (20-25 cm) in 18%, regular (25.1-32 cm) in 28%, large (32.1-40 cm) in 34%, and extra-large (40.1-55 cm) in 21%.
Dr. Brady pointed out that the most recent hypertension guidelines detail sources of inaccuracy in BP measurement and say that if too small a cuff size is used, the blood pressure could be different by 2 to 11 mm Hg. “And what we show, is it can be anywhere from 5 to 20 mm Hg. So, I think that’s a significant difference from what studies have shown so far and is going to be very surprising to clinicians.”
A 2019 AHA scientific statement on the measurement of blood pressure stresses the importance of cuff size, and last year, the American Medical Association launched a new initiative to standardize training in BP measurement for future physicians and health care professionals.
Previous work also showed that children as young as 3 to 5 years of age often require an adult cuff size, and those in the 12- to 15-year age group may need an extra-large cuff, or what is often referred to as a thigh cuff, said Dr. Brady, who is also the medical director of the pediatric hypertension program at Johns Hopkins Children’s Center.
“Part of the problem is that many physicians aren’t often the one doing the measurement and that others may not be as in tune with some of these data and initiatives,” she said.
Other barriers are cost and availability. Offices and clinics don’t routinely stock multiple cuff sizes in exam rooms, and devices sold over the counter typically come with a regular adult cuff, Dr. Brady said. An extra cuff could add $25 to $50 on top of the $25 to $50 for the device for the growing number of patients measuring BP remotely.
“During the pandemic, I was trying to do telemedicine with my hypertensive patients, but the children who had significant obesity couldn’t afford or find blood pressure devices that had a cuff that was big enough for them,” she said. “It just wasn’t something that they could get. So I think people just don’t recognize how important this is.”
A version of this article first appeared on Medscape.com.
Testicular cancer deaths rising among Hispanic men
, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.
Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.
The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.
“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”
She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.
“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”
“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
Details of the new findings
For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).
During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).
But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).
“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.
They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).
The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.
Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.
However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.
“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”
Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.
Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.
The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.
“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”
She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.
“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”
“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
Details of the new findings
For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).
During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).
But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).
“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.
They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).
The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.
Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.
However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.
“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”
Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.
Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.
The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.
“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”
She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.
“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”
“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
Details of the new findings
For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).
During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).
But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).
“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.
They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).
The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.
Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.
However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.
“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”
Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASCO GI 2022
Artificial intelligence aids assessment of UC activity, remission
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
FROM ECCO 2022
Endoscopic healing of Crohn’s disease could differ by biologic
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
FROM ECCO 2022
Azithromycin doesn’t prevent recurrent wheezing after acute infant RSV
Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.
Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.
The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.
Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.
“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.
And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.
“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”
He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.
In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
Study details
The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.
Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.
The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).
Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).
The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.
This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.
Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.
Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.
The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.
Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.
“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.
And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.
“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”
He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.
In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
Study details
The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.
Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.
The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).
Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).
The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.
This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.
Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.
Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.
The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.
Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.
“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.
And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.
“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”
He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.
In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
Study details
The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.
Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.
The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).
Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).
The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.
This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE–EVIDENCE
Robust immune response after COVID-19 boosters in those with IBD
Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.
“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.
“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.
Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
A study design to measure boosters’ benefits
For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”
They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.
Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.
Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.
Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.
Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.
Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.
“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
A ‘reassuring’ finding
“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.
The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.
The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.
“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.
A version of this article first appeared on Medscape.com.
Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.
“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.
“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.
Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
A study design to measure boosters’ benefits
For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”
They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.
Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.
Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.
Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.
Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.
Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.
“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
A ‘reassuring’ finding
“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.
The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.
The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.
“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.
A version of this article first appeared on Medscape.com.
Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.
“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.
“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.
Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
A study design to measure boosters’ benefits
For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”
They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.
Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.
Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.
Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.
Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.
Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.
“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
A ‘reassuring’ finding
“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.
The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.
The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.
“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.
A version of this article first appeared on Medscape.com.
FROM ECCO 2022
Evidence mounts for paramagnetic rim lesions in diagnosing MS
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research suggests.
Results from two studies add to the mounting evidence underscoring the importance of the imaging features, researchers noted. “Our data suggest that the presence and number of iron rim lesions hold a prognostic value for long-term disability in MS, especially the presence of four or more rim lesions,” said Amjad I. AlTokhis, School of Medicine, University of Nottingham, United Kingdom, and Division of Clinical Neuroscience, Nottingham University Hospitals NHS Trust, who was the lead author of both studies.
Importantly, the effect of the rim lesions on disability was greater than that of established prognostic biomarkers of T2 white matter lesion count and volume, she noted.
“This could support the use of iron rim lesions as an imaging biomarker for disease severity and worse prognosis,” said Dr. AlTokhis. “These findings also support that iron rim lesions might be clinically useful not only diagnostically but also for disease progression and predicting future disability in MS,” she added.
The findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022.
Sign of aggressive disease?
Dozens of studies have linked rim lesions, which are also known as iron rim lesions because of their composition of iron-laden macrophages/microglia, to more severe disease course in MS, as well as to having potential as an important imaging biomarker for diagnosis. However, studies have often been limited to smaller longitudinal cohorts.
In the first study, Dr. AlTokhis and colleagues enrolled 91 patients with MS (56 women) between 2008 and 2013 for whom 7 Tesla (7T) MRI was available with SWI-filtered phase sequencing.
At baseline, among 42 patients with clinically isolated syndrome, 50% had one or more of the rim lesions. The corresponding rates were 38% among 34 patients with relapsing-remitting MS, 38% among 18 patients with primary-progressive MS, and as high as 71% among 17 patients with secondary-progressive MS (P < .05 vs. primary progressive MS and clinically isolated syndrome).
At a median follow-up of 9 years, 18 of the patients with clinically isolated syndrome and relapsing-remitting MS progressed to secondary progressive MS; and among them, 56% had at least one rim lesion.
Of 24 who did not progress to secondary progressive MS, only 33% had at least one rim lesion.
The median baseline level of disease severity in the entire cohort, as measured by Age-Related Multiple Sclerosis Score (ARMSS), was 5.4. However, the median score among patients with rim lesions was higher, compared with those without the lesions (ARMSS, 6.7 vs. 5.0).
After the median 9-year follow-up, disease severity remained higher among those with versus those without the lesions (ARMSS, 7.3 vs. 6.3).
Patients with rim lesions had more white matter lesions overall; and a further analysis surprisingly showed that the number of rim lesions was indeed associated with long-term disability (P = .005).
“Detecting four or more iron rim lesions could be a sign of more aggressive disease and disability – thus, possibly useful in earlier treatment and a potential target for therapies,” Dr. AlTokhis said.
“Also, for clinical practicality, [the number of] iron rim lesions had the most direct effect on disability compared to white matter lesion count and volume, supporting its role as an independent prognostic imaging biomarker,” she added.
Dr. AlTokhis noted that “detecting and counting rim lesions is much easier than assessing all white matter lesions, adding to the clinical utility of this sign.”
Diagnostic value
The second study, presented at the meeting by coinvestigator Brian Renner, MD, Department of Neurology at Cedars Sinai, Los Angeles, reported on the significance of the rim lesions in MS diagnosis. It included 95 patients who had presented for new evaluation on suspicion of MS at 10 centers in the North American Imaging in MS Cooperative (NAIMS).
Of these participants, 44 (46%) were positively diagnosed according to McDonald 2017 criteria (MC2017) for MS, while 37 (39%) were given an alternative diagnosis to MS. Fourteen were considered at risk for MS with diagnoses of clinically isolating syndrome or radiologically isolating syndrome.
Overall, among the 44 with an MS diagnosis, 34 had one or more rim lesions; among the 51 who did not meet an MS diagnosis, only six had one or more of the rim lesions. One or more rim lesions were further observed in three patients with radiologically isolating syndrome and one patient with clinically isolating syndrome.
Among those with one or more of the rim lesions, a diagnosis of MS with MC2017 MS criteria was identified with a high sensitivity of 80%, high specificity of 88%, accuracy of 84%, and an AUC of 81%.
“We’ve shown that paramagnetic rim lesions are highly specific for MS, and the sensitivity of rim lesions for MS is higher than previously reported, despite similar techniques in rating, processing, and evaluation – which was likely related to the nature of the cohort,” Dr. Renner said.
Promising data
During the NAIMS symposium, Christopher C. Hemond, MD, assistant professor or neurology at the University of Massachusetts Medical School, Worcester, noted to meeting attendees that the rim lesions were seen across the entire course of the MS disease spectrum, spanning from radiologically isolating syndrome to secondary progressive MS.
“We know paramagnetic rim lesions are visible at all disease stages. They are uniquely larger and more destructive than their rimless peers and are associated with stronger disease severity,” said Dr. Hemond, who was not involved with the research.
“There is promising data at this point suggesting that [the rim lesions] may represent a biomarker predictive of future disability accumulation,” he added.
Dr. Hemond noted that, unlike in Dr. Renner’s study, the bulk of previous studies have indicated that rim lesions “are associated with a high specificity but only modest sensitivity, in the mid-50% range, for the diagnosis of MS in comparison to some conditions that mimic MS.”
Commenting on the findings, Dr. Hemond noted the results from Dr. Renner’s ongoing study “are critical in building confidence in the translational use of this biomarker to assist in ruling in a diagnosis of MS,” while Dr. AlTokis’ study “adds to and is consistent with the growing literature of pathological associations of paramagnetic rim lesions in MS.”
Dr. Hemond added that the NAIMS cooperative plans to publish guidance in the area in the coming months.
“Although paramagnetic rim lesions have strong pathological associations in MS, it remains unclear if the presence of these lesions should change MS clinical management at the present time,” he said.
During the NAIMS session, Francesca Bagnato, MD, PhD, Vanderbilt University Medical Center, Nashville, Tenn., noted the growing importance of the role of rim lesions in clinical research. “It is clear that these paramagnetic rim lesions are going to be the new biomarker for the next generation of clinical trials,” she said.
Dr. Renner’s study received funding from the Race to Erase MS Foundation. Dr. AlTokhis, Dr. Renner, and Dr. Hemond have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
REPORTING FROM ACTRIMS FORUM 2022
Spinal cord atrophy predicts ‘silent progression’ in MS
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
WEST PALM BEACH, FLA. – , new research shows. Study results suggest that this is a potentially important biomarker for disease progression that may otherwise go unrecognized by clinicians and patients, investigators noted.
“We found that cervical cord atrophy at the C1 level, as obtained from routine brain MRI, is the strongest indicator of silent progression and secondary progressive MS conversion,” said lead author Antje Bischof, MD, department of neurology and Institute of Translational Neurology, University Hospital, Munster, Germany.
“Silent progression and secondary progressive MS conversion are each predominantly related to spinal cord atrophy,” she added.
Dr. Bischof presented the findings at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Relatively new concept
Secondary progressive MS (SPMS) generally occurs when relapsing-remitting MS (RRMS) progresses, with relapses ceasing and a more steady accumulation of disability occurring.
However, a relapse-free “silent progression” of MS, described in previous research as occurring in as many as one-third or more of patients with relapsing MS, emerges at a much earlier stage prior to secondary progression. This potentially involves widespread neurodegeneration in early disease stages.
“Because the concept of silent progression is relatively new and directly challenges the long-accepted two-stage hypothesis, many clinicians have yet to actively identify silent progression in clinical practice,” said coinvestigator Bruce A. C. Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco).
To investigate the underlying structural or pathophysiologic changes that are linked to silent progression, the researchers focused on spinal cord measures, which are known to strongly correlate with disability.
They evaluated 360 patients with RRMS and 47 with SPMS and compared outcomes with 80 participants who acted as the study controls. The groups were matched for age, sex, disease duration, and treatments over a 12-year observation period using data from the UCSF MS Center.
To examine spinal cord changes in areas that could affect MS, the investigators used a novel orientation of MRI brain scans to capture the upper cervical cord area.
Among the patients with RRMS, 54 converted to SPMS over 12 years; 159 had silent progression during the period. Silent progression was defined as the onset of irreversible worsening of scores on the Expanded Disability Status Scale (EDSS). Silent progression was confirmed over 12 months and occurred independently of relapses.
‘Strongest predictor’
The analysis showed spinal cord atrophy at the C1 vertebral level to be the strongest predictor of silent progression, with each 1% increase in spinal cord atrophy associated with a 69% shorter time to silent clinical progression (P < .0001).
Those who converted from RRMS to SPMS showed spinal atrophy rates of –2.19% per year, versus –0.88% per year among those who did not convert (P < .001).
“C1A atrophy rates in patients with silent progression were faster even when combining RRMS and SPMS patients,” Dr. Bischof said.
Of note, the patients who silently progressed showed a lower EDSS score at baseline, she added.
Next to spinal atrophy, ventricular enlargement was the second strongest MRI metric associated with silent progression over the 12 years. Each 1% increase in lateral ventricle size was associated with a 16% reduced time to silent clinical progression (P = .007).
“These findings extend the prognostic value of spinal cord atrophy not only for the conversion to SPMS but also silent progression,” Dr. Bischof said. “Furthermore, we show that the enlargement of the lateral ventricles is the second strongest indicator of impending silent progression and the strongest of all brain measures,” she said.
Standard of care?
While the unique MRI techniques used in the study may not be easily obtained in standard practice, Dr. Cree noted that efforts are underway to facilitate the process. “Development of a fully automated software package to obtain those measurements for both clinical trials and in some [clinical settings] is underway,” he said.
Dr. Cree noted that once those technologies are available, the assessment of spinal cord atrophy could become standard in MS care. “I predict that when upper cervical cord measurements can be readily measured, assessment for decrease in the upper cervical cord area will be an essential component of routine care of relapsing MS patients,” he said.
“Because decreases in upper cervical cord areas herald disability worsening, there may well be a window of opportunity to use highly effective treatments to arrest or even reverse this process before irreversible disability accumulates,” Dr. Cree added.
Treatment implications
Commenting on the findings, ACTRIMS program cochair Anne Cross, MD, professor of neurology and the Manny and Rosalyn Rosenthal–Dr John Trotter MS Chair in Neuroimmunology, Washington University, St. Louis, noted that the study is important for two key reasons.
“We lack a good prognostic marker of future progression, but this could have very important implications for the choice of treatment of patients, particularly if the findings are applicable not only at the group level, as in the study, but also at the level of the individual patient,” said Dr. Cross, who was not involved with the research.
Secondly, the results suggest benefits in the selection of patients for clinical trials of agents that might stop progression. “Choosing patients who would deliver the most impact in studies of potential new treatments for progressive MS” is important, Dr. Cross said.
“We don’t want to dilute our trial patient populations with patients who might not be destined to progress in the ensuing years,” she added.
Also commenting on the findings, Benjamin Segal, MD, director of the University of Michigan’s Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, agreed that the study offers valuable insights. “These findings are striking in that they underscore the fact that even patients with relapsing-remitting MS undergo functional decline in between overt clinical exacerbations, although the decline is more subtle than that experienced by people with progressive forms of MS,” Dr. Segal said.
He noted that the strong correlation between silent progression and spinal cord atrophy, more so than with brain measures, “is not so surprising, since clinical decline was measured using the EDSS scale – which emphasizes ambulation over other functions,” such as cognition.
“It would be interesting to correlate silent progression with serum neurofilament light chain levels, at baseline as well as change over time,” Dr. Segal added.
Dr. Bischof and Dr. Segal have reported no relevant financial relationships. Dr. Cree has received personal compensation for consulting from Biogen, EMD Serono, and Novartis.
A version of this article first appeared on Medscape.com.
REPORTING FROM ACTRIMS FORUM 2022
IBD-VTE score serves as reminder to assess postdischarge risk
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
FROM ECCO 2022
Needle-free epinephrine products could be available in 2023
Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.
Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.”
Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.
Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).
Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall.
Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.
Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.
“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”
Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.
A version of this article first appeared on Medscape.com.
Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.
Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.”
Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.
Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).
Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall.
Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.
Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.
“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”
Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.
A version of this article first appeared on Medscape.com.
Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.
Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.”
Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.
Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).
Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall.
Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.
Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.
“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”
Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.
A version of this article first appeared on Medscape.com.
FROM AAAAI