TOPLINE:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” The authors declared no conflicts of interest.

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

TOPLINE:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” The authors declared no conflicts of interest.

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

TOPLINE:

Tumor necrosis factor (TNF) inhibitors are associated with a reduced risk for recurrent cardiovascular events in patients with radiographic axial spondyloarthritis (axSpA) and a history of cardiovascular events.

METHODOLOGY:

• The researchers conducted a nationwide cohort study using data from the Korean National Claims Database, including 413 patients diagnosed with cardiovascular events following a radiographic axSpA diagnosis.
• Of all patients, 75 received TNF inhibitors (mean age, 51.9 years; 92% men) and 338 did not receive TNF inhibitors (mean age, 60.7 years; 74.9% men).
• Patients were followed from the date of the first cardiovascular event to the date of recurrence, the last date with claims data, or up to December 2021.
• The study outcome was recurrent cardiovascular events that occurred within 28 days of the first incidence and included myocardial infarction and stroke.
• The effect of TNF inhibitor exposure on the risk for recurrent cardiovascular events was assessed using an inverse probability weighted Cox regression analysis.

TAKEAWAY:

• The incidence of recurrent cardiovascular events in patients with radiographic axSpA was 32 per 1000 person-years.
• The incidence was 19 per 1000 person-years in the patients exposed to TNF inhibitors, whereas it was 36 per 1000 person-years in those not exposed to TNF inhibitors.
• Exposure to TNF inhibitors was associated with a 67% lower risk for recurrent cardiovascular events than non-exposure (P = .038).

IN PRACTICE:

“Our data add to previous knowledge by providing more direct evidence that TNFi [tumor necrosis factor inhibitors] could reduce the risk of recurrent cardiovascular events,” the authors wrote.
 

SOURCE:

The study was led by Oh Chan Kwon, MD, PhD, and Hye Sun Lee, PhD, Yonsei University College of Medicine, Seoul, South Korea. It was published online on October 4, 2024, in Arthritis Research & Therapy.

LIMITATIONS:

The lack of data on certain cardiovascular risk factors such as obesity, smoking, and lifestyle may have led to residual confounding. The patient count in the TNF inhibitor exposure group was not adequate to analyze each TNF inhibitor medication separately. The study included only Korean patients, limiting the generalizability to other ethnic populations. The number of recurrent stroke events was relatively small, making it infeasible to analyze myocardial infarction and stroke separately.

DISCLOSURES:

The study was funded by Yuhan Corporation as part of its “2023 Investigator Initiated Translation Research Program.” The authors declared no conflicts of interest.

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

MOA — Mechanism of action — gets bandied about a lot.

Drug reps love it. Saying your product is a “first-in-class MOA” sounds great as they hand you a glossy brochure. It also features prominently in print ads, usually with pics of smiling people.

It’s a good thing to know, too, both medically and in a cool-science-geeky way. We want to understand what we’re prescribing will do to patients. We want to explain it to them, too.

It certainly helps to know that what we’re doing when treating a disorder using rational polypharmacy.

But at the same time we face the realization that it may not mean as much as we think it should. I don’t have to go back very far in my career to find Food and Drug Administration–approved medications that worked, but we didn’t have a clear reason why. I mean, we had a vague idea on a scientific basis, but we’re still guessing.

This didn’t stop us from using them, which is nothing new. The ancients had learned certain plants reduced pain and fever long before they understood what aspirin (and its MOA) was.

At the same time we’re now using drugs, such as the anti-amyloid treatments for Alzheimer’s disease, that should be more effective than one would think. Pulling the damaged molecules out of the brain should, on paper, make a dramatic difference ... but it doesn’t. I’m not saying they don’t have some benefit, but certainly not as much as you’d think. Of course, that’s based on our understanding of the disease mechanism being correct. We find there’s a lot more going on than we know.

Like so much in science (and this aspect of medicine is a science) the answers often lead to more questions.

Observation takes the lead over understanding in most things. Our ancestors knew what fire was, and how to use it, without any idea of what rapid exothermic oxidation was. (Admittedly, I have a degree in chemistry and can’t explain it myself anymore.)

The glossy ads and scientific data about MOA doesn’t mean much in my world if they don’t work. I’d rather have a drug that works, even if the MOA isn’t clear, than a known MOA without clinical benefit. My patients would say the same.

Clinical medicine, after all, is both an art and a science.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

MOA — Mechanism of action — gets bandied about a lot.

Drug reps love it. Saying your product is a “first-in-class MOA” sounds great as they hand you a glossy brochure. It also features prominently in print ads, usually with pics of smiling people.

It’s a good thing to know, too, both medically and in a cool-science-geeky way. We want to understand what we’re prescribing will do to patients. We want to explain it to them, too.

It certainly helps to know that what we’re doing when treating a disorder using rational polypharmacy.

But at the same time we face the realization that it may not mean as much as we think it should. I don’t have to go back very far in my career to find Food and Drug Administration–approved medications that worked, but we didn’t have a clear reason why. I mean, we had a vague idea on a scientific basis, but we’re still guessing.

This didn’t stop us from using them, which is nothing new. The ancients had learned certain plants reduced pain and fever long before they understood what aspirin (and its MOA) was.

At the same time we’re now using drugs, such as the anti-amyloid treatments for Alzheimer’s disease, that should be more effective than one would think. Pulling the damaged molecules out of the brain should, on paper, make a dramatic difference ... but it doesn’t. I’m not saying they don’t have some benefit, but certainly not as much as you’d think. Of course, that’s based on our understanding of the disease mechanism being correct. We find there’s a lot more going on than we know.

Like so much in science (and this aspect of medicine is a science) the answers often lead to more questions.

Observation takes the lead over understanding in most things. Our ancestors knew what fire was, and how to use it, without any idea of what rapid exothermic oxidation was. (Admittedly, I have a degree in chemistry and can’t explain it myself anymore.)

The glossy ads and scientific data about MOA doesn’t mean much in my world if they don’t work. I’d rather have a drug that works, even if the MOA isn’t clear, than a known MOA without clinical benefit. My patients would say the same.

Clinical medicine, after all, is both an art and a science.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

MOA — Mechanism of action — gets bandied about a lot.

Drug reps love it. Saying your product is a “first-in-class MOA” sounds great as they hand you a glossy brochure. It also features prominently in print ads, usually with pics of smiling people.

It’s a good thing to know, too, both medically and in a cool-science-geeky way. We want to understand what we’re prescribing will do to patients. We want to explain it to them, too.

It certainly helps to know that what we’re doing when treating a disorder using rational polypharmacy.

But at the same time we face the realization that it may not mean as much as we think it should. I don’t have to go back very far in my career to find Food and Drug Administration–approved medications that worked, but we didn’t have a clear reason why. I mean, we had a vague idea on a scientific basis, but we’re still guessing.

This didn’t stop us from using them, which is nothing new. The ancients had learned certain plants reduced pain and fever long before they understood what aspirin (and its MOA) was.

At the same time we’re now using drugs, such as the anti-amyloid treatments for Alzheimer’s disease, that should be more effective than one would think. Pulling the damaged molecules out of the brain should, on paper, make a dramatic difference ... but it doesn’t. I’m not saying they don’t have some benefit, but certainly not as much as you’d think. Of course, that’s based on our understanding of the disease mechanism being correct. We find there’s a lot more going on than we know.

Like so much in science (and this aspect of medicine is a science) the answers often lead to more questions.

Observation takes the lead over understanding in most things. Our ancestors knew what fire was, and how to use it, without any idea of what rapid exothermic oxidation was. (Admittedly, I have a degree in chemistry and can’t explain it myself anymore.)

The glossy ads and scientific data about MOA doesn’t mean much in my world if they don’t work. I’d rather have a drug that works, even if the MOA isn’t clear, than a known MOA without clinical benefit. My patients would say the same.

Clinical medicine, after all, is both an art and a science.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

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

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

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

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

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

The study was published online in CMAJ.
 

Vaccination Program Changes

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

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

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

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

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

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

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

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

What Next?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in CMAJ.
 

Vaccination Program Changes

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

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

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

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

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

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

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

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

What Next?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in CMAJ.
 

Vaccination Program Changes

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

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

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

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

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

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

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

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

What Next?

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

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

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

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

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

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

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

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

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

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

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Food and Drug Administration (FDA) has approved Hympavzi (marstacimab, Pfizer) as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients 12 years or older who have hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors.

The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.

“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release. 

Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A. 

The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors. 

During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year. 

Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi. 

Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.

Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes. 

Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April. 

Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
 

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

The Food and Drug Administration (FDA) has approved Hympavzi (marstacimab, Pfizer) as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients 12 years or older who have hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors.

The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.

“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release. 

Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A. 

The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors. 

During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year. 

Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi. 

Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.

Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes. 

Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April. 

Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
 

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

The Food and Drug Administration (FDA) has approved Hympavzi (marstacimab, Pfizer) as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients 12 years or older who have hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors.

The once-weekly subcutaneous injection targets an anticoagulation protein called tissue factor pathway inhibitor (TFPI). Reducing TFPI’s amount and activity in the blood subsequently increases the amount of thrombin, a pro-clotting enzyme, in circulation.

“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” Ann Farrell, MD, director of FDA’s Division of Non-Malignant Hematology, said in an agency press release. 

Hympavzi is the first non-factor, once-weekly treatment for hemophilia B in the United States. The subcutaneous injection emicizumab (Hemlibra, Genentech), which works by a different mechanism, is already on the market for hemophilia A. 

The current approval was based on the open-label BASIS trial in 116 men and boys with either severe hemophilia A or B without factor inhibitors. 

During the trial’s first 6 months, patients received standard treatment with clotting factor replacement either on-demand (33 patients) or prophylactically (83 patients). Patients were then switched to Hympavzi prophylaxis for a year. 

Among patients receiving on-demand standard treatment during the first 6 months, the annualized bleeding rate was 38 episodes. That rate fell to 3.2 episodes during treatment with Hympavzi. 

Among patients receiving prophylactic standard treatment during the first 6 months, the estimated annualized bleeding rate was 7.85 episodes, which then fell to 5.08 during the year of Hympavzi prophylaxis, FDA said.

Injection-site reactions, headaches, and itching were the most common side effects with marstacimab, occurring in 3% or more of patients. Labeling warns of the potential for circulating blood clots, hypersensitivity, and embryofetal toxicity. Marstacimab is supplied in prefilled syringes. 

Marstacimab is Pfizer’s second hemophilia approval in 2024. FDA approved the company’s hemophilia B gene therapy fidanacogene elaparvovec (Beqvez) in April. 

Pfizer noted in a press release that results for another arm of the BASIS trial in patients with clotting factor inhibitors are expected in 2025.
 

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

TOPLINE:

Genetic predisposition to gout, unfavorable lifestyle habits, and poor metabolic health are associated with an increased risk for cardiovascular disease (CVD); however, adherence to a healthy lifestyle can reduce this risk by up to 62%, even in individuals with high genetic risk.

METHODOLOGY:

• Researchers investigated the association between genetic predisposition to gout, combined with lifestyle habits, and the risk for CVD in two diverse prospective cohorts from different ancestral backgrounds.
• They analyzed the data of 224,689 participants of European descent from the UK Biobank (mean age, 57.0 years; 56.1% women) and 50,364 participants of East Asian descent from the Korean Genome and Epidemiology Study (KoGES; mean age, 53.7 years; 66.0% women).
• The genetic predisposition to gout was evaluated using a polygenic risk score (PRS) derived from a metagenome-wide association study, and the participants were categorized into low, intermediate, and high genetic risk groups based on their PRS for gout.
• A favorable lifestyle was defined as having ≥ 3 healthy lifestyle factors, and 0-1 metabolic syndrome factor defined the ideal metabolic health status.
• The incident CVD risk was evaluated according to genetic risk, lifestyle habits, and metabolic syndrome.

TAKEAWAY:

• Individuals in the high genetic risk group had a higher risk for CVD than those in the low genetic risk group in both the UK Biobank (adjusted hazard ratio [aHR], 1.10; P < .001) and KoGES (aHR, 1.31; P = .024) cohorts.
• In the UK Biobank cohort, individuals with a high genetic risk for gout and unfavorable lifestyle choices had a 1.99 times higher risk for incident CVD than those with low genetic risk (aHR, 1.99; P < .001); similar outcomes were observed in the KoGES cohort.
• Similarly, individuals with a high genetic risk for gout and poor metabolic health in the UK Biobank cohort had a 2.16 times higher risk for CVD than those with low genetic risk (aHR, 2.16; P < .001 for both); outcomes were no different in the KoGES cohort.
• Improving metabolic health and adhering to a healthy lifestyle reduced the risk for CVD by 62% in individuals with high genetic risk and by 46% in those with low genetic risk (P < .001 for both).

IN PRACTICE:

“PRS for gout can be used for preventing not only gout but also CVD. It is possible to identify individuals with high genetic risk for gout and strongly recommend modifying lifestyle habits. Weight reduction, smoking cessation, regular exercise, and eating healthy food are effective strategies to prevent gout and CVD,” the authors wrote.

SOURCE:

This study was led by Ki Won Moon, MD, PhD, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea, and SangHyuk Jung, PhD, University of Pennsylvania, Philadelphia, and was published online on October 8, 2024, in RMD Open.

LIMITATIONS: 

The definitions of lifestyle and metabolic syndrome were different in each cohort, which may have affected the findings. Data on lifestyle behaviors and metabolic health statuses were collected at enrollment, but these variables may have changed during the follow-up period, which potentially introduced bias into the results. This study was not able to establish causality between genetic predisposition to gout and the incident risk for CVD.

DISCLOSURES:

This study was supported by the National Institute of General Medical Sciences and the National Research Foundation of Korea. The authors declared no competing interests.

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

TOPLINE:

Genetic predisposition to gout, unfavorable lifestyle habits, and poor metabolic health are associated with an increased risk for cardiovascular disease (CVD); however, adherence to a healthy lifestyle can reduce this risk by up to 62%, even in individuals with high genetic risk.

METHODOLOGY:

• Researchers investigated the association between genetic predisposition to gout, combined with lifestyle habits, and the risk for CVD in two diverse prospective cohorts from different ancestral backgrounds.
• They analyzed the data of 224,689 participants of European descent from the UK Biobank (mean age, 57.0 years; 56.1% women) and 50,364 participants of East Asian descent from the Korean Genome and Epidemiology Study (KoGES; mean age, 53.7 years; 66.0% women).
• The genetic predisposition to gout was evaluated using a polygenic risk score (PRS) derived from a metagenome-wide association study, and the participants were categorized into low, intermediate, and high genetic risk groups based on their PRS for gout.
• A favorable lifestyle was defined as having ≥ 3 healthy lifestyle factors, and 0-1 metabolic syndrome factor defined the ideal metabolic health status.
• The incident CVD risk was evaluated according to genetic risk, lifestyle habits, and metabolic syndrome.

TAKEAWAY:

• Individuals in the high genetic risk group had a higher risk for CVD than those in the low genetic risk group in both the UK Biobank (adjusted hazard ratio [aHR], 1.10; P < .001) and KoGES (aHR, 1.31; P = .024) cohorts.
• In the UK Biobank cohort, individuals with a high genetic risk for gout and unfavorable lifestyle choices had a 1.99 times higher risk for incident CVD than those with low genetic risk (aHR, 1.99; P < .001); similar outcomes were observed in the KoGES cohort.
• Similarly, individuals with a high genetic risk for gout and poor metabolic health in the UK Biobank cohort had a 2.16 times higher risk for CVD than those with low genetic risk (aHR, 2.16; P < .001 for both); outcomes were no different in the KoGES cohort.
• Improving metabolic health and adhering to a healthy lifestyle reduced the risk for CVD by 62% in individuals with high genetic risk and by 46% in those with low genetic risk (P < .001 for both).

IN PRACTICE:

“PRS for gout can be used for preventing not only gout but also CVD. It is possible to identify individuals with high genetic risk for gout and strongly recommend modifying lifestyle habits. Weight reduction, smoking cessation, regular exercise, and eating healthy food are effective strategies to prevent gout and CVD,” the authors wrote.

SOURCE:

This study was led by Ki Won Moon, MD, PhD, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea, and SangHyuk Jung, PhD, University of Pennsylvania, Philadelphia, and was published online on October 8, 2024, in RMD Open.

LIMITATIONS: 

The definitions of lifestyle and metabolic syndrome were different in each cohort, which may have affected the findings. Data on lifestyle behaviors and metabolic health statuses were collected at enrollment, but these variables may have changed during the follow-up period, which potentially introduced bias into the results. This study was not able to establish causality between genetic predisposition to gout and the incident risk for CVD.

DISCLOSURES:

This study was supported by the National Institute of General Medical Sciences and the National Research Foundation of Korea. The authors declared no competing interests.

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

TOPLINE:

Genetic predisposition to gout, unfavorable lifestyle habits, and poor metabolic health are associated with an increased risk for cardiovascular disease (CVD); however, adherence to a healthy lifestyle can reduce this risk by up to 62%, even in individuals with high genetic risk.

METHODOLOGY:

• Researchers investigated the association between genetic predisposition to gout, combined with lifestyle habits, and the risk for CVD in two diverse prospective cohorts from different ancestral backgrounds.
• They analyzed the data of 224,689 participants of European descent from the UK Biobank (mean age, 57.0 years; 56.1% women) and 50,364 participants of East Asian descent from the Korean Genome and Epidemiology Study (KoGES; mean age, 53.7 years; 66.0% women).
• The genetic predisposition to gout was evaluated using a polygenic risk score (PRS) derived from a metagenome-wide association study, and the participants were categorized into low, intermediate, and high genetic risk groups based on their PRS for gout.
• A favorable lifestyle was defined as having ≥ 3 healthy lifestyle factors, and 0-1 metabolic syndrome factor defined the ideal metabolic health status.
• The incident CVD risk was evaluated according to genetic risk, lifestyle habits, and metabolic syndrome.

TAKEAWAY:

• Individuals in the high genetic risk group had a higher risk for CVD than those in the low genetic risk group in both the UK Biobank (adjusted hazard ratio [aHR], 1.10; P < .001) and KoGES (aHR, 1.31; P = .024) cohorts.
• In the UK Biobank cohort, individuals with a high genetic risk for gout and unfavorable lifestyle choices had a 1.99 times higher risk for incident CVD than those with low genetic risk (aHR, 1.99; P < .001); similar outcomes were observed in the KoGES cohort.
• Similarly, individuals with a high genetic risk for gout and poor metabolic health in the UK Biobank cohort had a 2.16 times higher risk for CVD than those with low genetic risk (aHR, 2.16; P < .001 for both); outcomes were no different in the KoGES cohort.
• Improving metabolic health and adhering to a healthy lifestyle reduced the risk for CVD by 62% in individuals with high genetic risk and by 46% in those with low genetic risk (P < .001 for both).

IN PRACTICE:

“PRS for gout can be used for preventing not only gout but also CVD. It is possible to identify individuals with high genetic risk for gout and strongly recommend modifying lifestyle habits. Weight reduction, smoking cessation, regular exercise, and eating healthy food are effective strategies to prevent gout and CVD,” the authors wrote.

SOURCE:

This study was led by Ki Won Moon, MD, PhD, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea, and SangHyuk Jung, PhD, University of Pennsylvania, Philadelphia, and was published online on October 8, 2024, in RMD Open.

LIMITATIONS: 

The definitions of lifestyle and metabolic syndrome were different in each cohort, which may have affected the findings. Data on lifestyle behaviors and metabolic health statuses were collected at enrollment, but these variables may have changed during the follow-up period, which potentially introduced bias into the results. This study was not able to establish causality between genetic predisposition to gout and the incident risk for CVD.

DISCLOSURES:

This study was supported by the National Institute of General Medical Sciences and the National Research Foundation of Korea. The authors declared no competing interests.

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

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

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

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

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

TOPLINE:

Both low and high levels of maternal 25-hydroxy [25(OH)] vitamin D are linked to an increased risk for adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with levels of 40-59 ng/mL being associated with the lowest risk.

METHODOLOGY:

• Researchers analyzed 260 pregnancies in the Hopkins Lupus Cohort to examine the association between 25(OH) vitamin D levels and adverse pregnancy outcomes in women with SLE.
• The participants were required to have serum vitamin D levels measured during pregnancy and pregnancy-related outcomes data.
• The 25(OH) vitamin D levels were measured at visits every 6 weeks, and the participants were divided into six subgroups on the basis of the mean 25(OH) vitamin D levels: < 20 ng/dL, 20-29 ng/dL, 30-39 ng/dL, 40-49 ng/dL, 50-59 ng/dL, and ≥ 60 ng/dL.
• The adverse pregnancy outcomes included miscarriage, preterm delivery, and restricted intrauterine growth of the fetus.
• This study used a time-to-event analysis to assess the association between time-varying 25(OH) vitamin D levels and adverse pregnancy outcomes.

TAKEAWAY:

• Adverse pregnancy outcomes were observed in 45.3% of pregnancies; the risks for miscarriage and preterm delivery were significantly different across the six subgroups with varying vitamin D levels (P = .0045 and P = .0007, respectively).
• A U-shaped curve association was observed between vitamin D levels and adverse pregnancy outcomes, with the highest risk seen in patients with the lowest or highest levels of vitamin D during pregnancy, while the lowest risk was seen in those with vitamin D levels between 40 and 59 ng/mL.
• Low 25(OH) vitamin D levels during the second trimester resulted in premature delivery in 9 out of 10 pregnancies; however, a relationship between vitamin D levels in the first trimester and pregnancy outcomes was not observed.
• The time-to-event analysis showed that the U-shaped association between vitamin D levels and adverse pregnancy outcomes was still observed even after accounting for lupus disease activity; however, the elevated risk seen in individuals with the highest levels of vitamin D was no longer statistically significant.

IN PRACTICE:

“We recommend monitoring of maternal serum 25(OH) vitamin D levels throughout SLE pregnancies and supplementing patients with vitamin D insufficiency or deficiency, aiming for 25(OH) vitamin D range of 40-59 ng/mL. Over supplementation should be avoided,” the authors wrote.

SOURCE:

The study was led by Nima Madanchi, MD, Johns Hopkins University, Baltimore, and was published online on September 23, 2024, in Arthritis Care & Research.

LIMITATIONS:

This study could not prove a cause-and-effect relationship between vitamin D levels and adverse pregnancy outcomes. This study included only clinically identified pregnancies, potentially missing very early miscarriages. It also could not adjust for parity due to the unknown parity of the index pregnancy.

DISCLOSURES:

This Hopkins Lupus Cohort was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
 

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