Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Campaigners for greater transparency in medical science have reiterated calls for more to be done to avoid “medical research waste” after an investigation found that results from more than a fifth of clinical trials across five Nordic countries have never been made public.

A study found that results from 475 clinical trials in Denmark, Iceland, Finland, Norway, and Sweden — involving almost 84,000 participants — were never made public in any form.

Nonpublication of clinical trial results wastes public money, harms patients, and undermines public health, the researchers said. 

There is already a well-defined ethical responsibility to publish trial results. Article 36 of the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects states that “researchers have a duty to make publicly available the results of their research on human subjects,” and World Health Organization best practice protocols call for results to be uploaded onto trial registries within 12 months of trial completion.
 

Research Waste Is a ‘Pervasive Problem’

So, how and why do so many trials end up gathering dust in a drawer? The latest study, published February 5 as a preprint, evaluated the reporting outcomes of 2113 clinical trials at medical universities and university hospitals in Nordic countries between 2016 and 2019. It found that across the five countries, 22% of all clinical trial results had not been shared. Furthermore, only 27% of all trial results were made public, either on registries or in journals, within 12 months. Even 2 years after trials ended, only around half of results (51.7%) had been put into the public domain.

The authors concluded that missing and delayed results from academically-led clinical trials was a “pervasive problem” in Nordic countries and that institutions, funding bodies, and policymakers needed to ensure that regulations around reporting results were adhered to so that important findings are not lost.

Study first author, Gustav Nilsonne, MD, PHD, from the Department of Clinical Neuroscience at the Karolinska Institutet, Sweden, told this news organization: “Most people I talk to — most colleagues who are clinical scientists — tend to think that the main reason is that negative results are not as interesting to publish and therefore they get lower priority, and they get published later and sometimes not at all.”

Experts stressed that the problem is not confined to Nordic countries and that wasted medical research persists elsewhere in Europe and remains a global problem. For instance, a report published in the Journal of Clinical Epidemiology found that 30% of German trials completed between 2014 and 2017 remained unpublished 5 years after completion.
 

The Case for Laws, Monitoring, and Fines

Till Bruckner, PHD, from TranspariMED, which campaigns to end evidence distortion in medicine, told this news organization: “What is needed to comprehensively fix the problem is a national legal requirement to make all trial results public, coupled with effective monitoring, and followed by sanctions in the rare cases where institutions refuse to comply.” 

Dr. Nilsonne added: “We have argued that the sponsors need to take greater responsibility, but also that there needs to be somebody whose job it is to monitor clinical trials reporting. It shouldn’t have to be that we do this as researchers on a shoestring with no dedicated resources. It should be somebody’s job.”

Since January 31, 2023, all initial clinical trial applications in the European Union must be submitted through the EU Clinical Trials Information System. Dr. Bruckner said that “the picture is not yet clear” in Europe, as the first trial results under the system are not expected until later this year. Even then, enforcement lies with regulators in individual countries. And while Denmark has already indicated it will enforce the regulations, he warned that other countries “might turn a blind eye.”

He pointed out that existing laws don’t apply to all types of trials. “That means that for many trials, nobody is legally responsible for ensuring that results are made public, and no government agency has any oversight or mandate,” he said.

Outside the EU, the United Kingdom has helped lead the way through the NHS Health Research Authority (HRA), which registers trials run in the country. One year after a trial has been completed, the HRA checks to see if the results have been uploaded to the registry and issues reminders if they haven’t.

In an update of its work in January, the authority said that compliance had hovered at just below 90% between 2018 and 2021 but that it was working to increase this to 100% by working with stakeholders across the research sector.

Dr. Nilsonne considers the UK system of central registration and follow-up an attractive option. “I would love to see something along those lines in other countries too,” he said.
 

‘Rampant Noncompliance’ in the United States

In the United States, a requirement to make trial results public is backed by law. Despite this, there’s evidence of “rampant noncompliance” and minimal government action, according to Megan Curtin from Universities Allied for Essential Medicines (UAEM), which has been tracking the issue in the United States and working to push universities and others to make their findings available.

The US Food and Drug Administration (FDA) shares responsibility with the National Institutes of Health for enforcement of clinical trial results reporting, but the UAEM says nearly 4000 trials are currently out of compliance with reporting requirements. In January last year, the UAEM copublished a report with the National Center for Health Research and TranspariMED, which found that 3627 American children participated in clinical trials whose results remain unreported.

The FDA can levy a fine of up to $10,000 USD for a violation of the law, but UAEM said that, as of January 2023, the FDA had sent only 92 preliminary notices of noncompliance and four notices of noncompliance. “A clear difference between the EU field of clinical trial operation and US clinical trials is that there are clear laws for reporting within 12 months, which can be enforced, but they’re not being enforced by the FDA,” Ms. Curtin told this news organization.

The UAEM is pushing the FDA to issue a minimum of 250 preliminary notices of noncompliance each year to noncompliant trial sponsors.

Dr. Nilsonne said: “I do believe we have a great responsibility to the patients that do contribute. We need to make sure that the harms and risks that a clinical trial entails are really balanced by knowledge gain, and if the results are never reported, then we can’t have a knowledge gain.”
 

A version of this article appeared on Medscape.com.

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

The chemotherapy drug asparaginase revolutionized childhood cancer care in the 1970s, and it’s still a mainstay of treatment for acute lymphoblastic leukemia (ALL) today. But asparaginase remains difficult for some to tolerate, and clinicians keep needing to adjust therapy to address toxicity.

The good news, hematologists note, is that new strategies have been developed to address side effects. “We’ve gotten better at managing them,” pediatric oncologist Birte Wistinghausen, MD, of Children’s National Hospital in Washington, DC, said in an interview.

According to her, key approaches include sensitivity testing and “pre-medication” to prevent adverse effects from appearing in the first place.

The American Cancer Society estimates that 6,550 new cases of ALL appear in the United States each year, and 1,330 people die from the disease.

“Most cases of ALL occur in children, but most deaths from ALL (about 4 out of 5) occur in adults,” the organization reports. Indeed, the 5-year survival rate in children is now at about 90%, a number that hematologists partially attribute to the power of asparaginase.

Researchers believe that asparaginase, an enzyme, works by breaking down a substance called asparagine, which ALL cells use to reproduce. The drug is “universally used throughout the treatment of ALL in children and adolescents,” Luke Maese, DO, associate professor of pediatrics at the University of Utah–Huntsman Cancer Institute, Salt Lake City, and director of Leukemia/Lymphoma at Primary Children’s Hospital, said in an interview. “It has become more and more adopted in the treatment of young adults as well.”

The formulations of available asparaginase have evolved over the years, Dr. Maese said. “Currently, the first-line asparaginase products delivered in the majority of patients throughout the world are pegylated, meaning they have an extended duration of action. There are non-pegylated asparaginase products that are used as well.”

The pegylated drugs are much easier on patients since they don’t require frequent injections, according to experts.

Treatment protocols vary, Dr. Maese said. “Some use the drug intermittently intermixed throughout therapy, and others have periods of continuous asparaginase use — i.e. 10-20 weeks of repeated doses of the drug.”

All patients are likely to experience side effects, he said, and about 5%-10% of standard-risk and 20%-25% of high-risk patients will experience clinically significant problems.

When asparaginase is given by IV, its rapid onset can lead to a condition called acute hyperammonemia, in which ammonia levels rise and patients develop flushing, anxiety, and low blood pressure, said Dr. Wistinghausen of Children’s National Hospital. “But that is not a reason to abandon asparaginase.”

It can be difficult to differentiate this effect from hypersensitivity — allergic reactions — which can range from hives to full anaphylactic shock that requires treatment with epinephrine, she said.

According to Dr. Maese, other major side effects other than hypersensitivity include pancreatitis, hepatotoxicity, and thrombosis. The most dangerous of these side effects are hypersensitivity and pancreatitis, which can lead to discontinuation of treatment, he said. Indeed, a 2017 study found that 2% of 465 patients with ALL who developed asparaginase-associated pancreatitis died, and 8% needed mechanical ventilation.

There’s no way to predict which patients may be susceptible to pancreatitis, Michael J. Burke, MD, professor of pediatrics and director of leukemia/lymphoma director at Children’s Wisconsin and Medical College of Wisconsin, said in an interview.

As for therapy options if pancreatitis develops, a 2022 review cowritten by Dr. Maese reported that clinicians have been leaning toward re-treating patients with asparaginase since it’s so crucial to treatment. This has worked about 50% of the time, the review reported, and “many groups consider it in the setting of all grade 2 pancreatitis and grade 3 pancreatitis without prolonged illness or severe complications.”

As for hypersensitivity, the most prevalent adverse effect, clinicians frequently administer anti-allergy medications prior to infusion. This approach, known as “pre-medication,” is controversial. Research has produced conflicting results, with a 2022 study in the journal Blood finding that pre-medication had no effect on hypersensitivity in children with ALL.

“Although there is mixed data, most institutions utilize this,” Dr. Maese said. “At our institution, we continue to use pre-medication prior to pegylated asparaginase but do not use it with non-pegylated asparaginase.”

Specifically, most institutions administer H2 and H1 blockers, Dr. Wistinghausen said. “Some institutions also use hydrocortisone” — a steroid — “but our institution only uses it if patients have a reaction.”

Other potential adverse effects to treatment include infusion reactions, which can mimic allergic reactions such as nausea, vomiting, abdominal pain, and flushing, Dr. Maese said.

Asked how to treat patients who cannot tolerate first-line treatment with asparaginase, Dr. Burke responded, “There are second-generation asparaginase formulations for once a patient develops an allergy.”

Dr. Maese said his institution switches patients when necessary to asparaginase Erwinia chrysanthemi (recombinant)-rywn, also known as Rylaze.

Another recent development in ALL treatment is the widespread use of drug monitoring to make sure asparaginase is reaching therapeutic levels. “Asparagine itself is difficult to measure so we use a surrogate of asparaginase levels to demonstrate efficacy of the drug,” he said. “There is conflicting literature as to what constitutes a therapeutic level, but the internationally accepted standard is a level of ≥ 0.1 IU/mL. We monitor asparaginase levels routinely with pegylated asparaginase but not with non-pegylated asparaginase.”

Tests can turn up “silent inactivation,” a term that refers to when the drug is “inactivated” and is not effective, Dr. Maese said. “There are several guidelines that have defined inactivation.” According to the 2022 report cowritten by Dr. Maese, Rylaze can be an alternative option if initial asparaginase treatment isn’t working.

With regard to cost, treatment with asparaginase can cost tens of thousands of dollars. However, insurers routinely pay for treatment plus pre-medication and testing, Dr. Burke said. “There’s no pushback. It seems to be accepted.”

What’s next on the horizon? “We need to understand better those patients who are at risk for toxicity,” Dr. Maese noted. “We understand obesity causes risk for certain toxicities, but have little else to go on. There has been some work with genomics and its relationship to risk of toxicity. However, it has been difficult to translate what has been found to patients.”

There’s work in progress that is exploring other preventive approaches to decrease toxicity, he said. Also, “optimizing the dosing of asparaginase has been explored more in Europe and within a smaller consortium in North America.”

In addition, he said, “as we begin to increase use of immunotherapy within our chemotherapy backbones, we need to understand the relationship these drugs have with asparaginase treatment.”

Dr. Burke and Dr. Wistinghausen have no disclosures. Dr. Maese discloses relationships with Jazz (advisory board, consultant, speakers bureau) and Servier (advisory board).

The chemotherapy drug asparaginase revolutionized childhood cancer care in the 1970s, and it’s still a mainstay of treatment for acute lymphoblastic leukemia (ALL) today. But asparaginase remains difficult for some to tolerate, and clinicians keep needing to adjust therapy to address toxicity.

The good news, hematologists note, is that new strategies have been developed to address side effects. “We’ve gotten better at managing them,” pediatric oncologist Birte Wistinghausen, MD, of Children’s National Hospital in Washington, DC, said in an interview.

According to her, key approaches include sensitivity testing and “pre-medication” to prevent adverse effects from appearing in the first place.

The American Cancer Society estimates that 6,550 new cases of ALL appear in the United States each year, and 1,330 people die from the disease.

“Most cases of ALL occur in children, but most deaths from ALL (about 4 out of 5) occur in adults,” the organization reports. Indeed, the 5-year survival rate in children is now at about 90%, a number that hematologists partially attribute to the power of asparaginase.

Researchers believe that asparaginase, an enzyme, works by breaking down a substance called asparagine, which ALL cells use to reproduce. The drug is “universally used throughout the treatment of ALL in children and adolescents,” Luke Maese, DO, associate professor of pediatrics at the University of Utah–Huntsman Cancer Institute, Salt Lake City, and director of Leukemia/Lymphoma at Primary Children’s Hospital, said in an interview. “It has become more and more adopted in the treatment of young adults as well.”

The formulations of available asparaginase have evolved over the years, Dr. Maese said. “Currently, the first-line asparaginase products delivered in the majority of patients throughout the world are pegylated, meaning they have an extended duration of action. There are non-pegylated asparaginase products that are used as well.”

The pegylated drugs are much easier on patients since they don’t require frequent injections, according to experts.

Treatment protocols vary, Dr. Maese said. “Some use the drug intermittently intermixed throughout therapy, and others have periods of continuous asparaginase use — i.e. 10-20 weeks of repeated doses of the drug.”

All patients are likely to experience side effects, he said, and about 5%-10% of standard-risk and 20%-25% of high-risk patients will experience clinically significant problems.

When asparaginase is given by IV, its rapid onset can lead to a condition called acute hyperammonemia, in which ammonia levels rise and patients develop flushing, anxiety, and low blood pressure, said Dr. Wistinghausen of Children’s National Hospital. “But that is not a reason to abandon asparaginase.”

It can be difficult to differentiate this effect from hypersensitivity — allergic reactions — which can range from hives to full anaphylactic shock that requires treatment with epinephrine, she said.

According to Dr. Maese, other major side effects other than hypersensitivity include pancreatitis, hepatotoxicity, and thrombosis. The most dangerous of these side effects are hypersensitivity and pancreatitis, which can lead to discontinuation of treatment, he said. Indeed, a 2017 study found that 2% of 465 patients with ALL who developed asparaginase-associated pancreatitis died, and 8% needed mechanical ventilation.

There’s no way to predict which patients may be susceptible to pancreatitis, Michael J. Burke, MD, professor of pediatrics and director of leukemia/lymphoma director at Children’s Wisconsin and Medical College of Wisconsin, said in an interview.

As for therapy options if pancreatitis develops, a 2022 review cowritten by Dr. Maese reported that clinicians have been leaning toward re-treating patients with asparaginase since it’s so crucial to treatment. This has worked about 50% of the time, the review reported, and “many groups consider it in the setting of all grade 2 pancreatitis and grade 3 pancreatitis without prolonged illness or severe complications.”

As for hypersensitivity, the most prevalent adverse effect, clinicians frequently administer anti-allergy medications prior to infusion. This approach, known as “pre-medication,” is controversial. Research has produced conflicting results, with a 2022 study in the journal Blood finding that pre-medication had no effect on hypersensitivity in children with ALL.

“Although there is mixed data, most institutions utilize this,” Dr. Maese said. “At our institution, we continue to use pre-medication prior to pegylated asparaginase but do not use it with non-pegylated asparaginase.”

Specifically, most institutions administer H2 and H1 blockers, Dr. Wistinghausen said. “Some institutions also use hydrocortisone” — a steroid — “but our institution only uses it if patients have a reaction.”

Other potential adverse effects to treatment include infusion reactions, which can mimic allergic reactions such as nausea, vomiting, abdominal pain, and flushing, Dr. Maese said.

Asked how to treat patients who cannot tolerate first-line treatment with asparaginase, Dr. Burke responded, “There are second-generation asparaginase formulations for once a patient develops an allergy.”

Dr. Maese said his institution switches patients when necessary to asparaginase Erwinia chrysanthemi (recombinant)-rywn, also known as Rylaze.

Another recent development in ALL treatment is the widespread use of drug monitoring to make sure asparaginase is reaching therapeutic levels. “Asparagine itself is difficult to measure so we use a surrogate of asparaginase levels to demonstrate efficacy of the drug,” he said. “There is conflicting literature as to what constitutes a therapeutic level, but the internationally accepted standard is a level of ≥ 0.1 IU/mL. We monitor asparaginase levels routinely with pegylated asparaginase but not with non-pegylated asparaginase.”

Tests can turn up “silent inactivation,” a term that refers to when the drug is “inactivated” and is not effective, Dr. Maese said. “There are several guidelines that have defined inactivation.” According to the 2022 report cowritten by Dr. Maese, Rylaze can be an alternative option if initial asparaginase treatment isn’t working.

With regard to cost, treatment with asparaginase can cost tens of thousands of dollars. However, insurers routinely pay for treatment plus pre-medication and testing, Dr. Burke said. “There’s no pushback. It seems to be accepted.”

What’s next on the horizon? “We need to understand better those patients who are at risk for toxicity,” Dr. Maese noted. “We understand obesity causes risk for certain toxicities, but have little else to go on. There has been some work with genomics and its relationship to risk of toxicity. However, it has been difficult to translate what has been found to patients.”

There’s work in progress that is exploring other preventive approaches to decrease toxicity, he said. Also, “optimizing the dosing of asparaginase has been explored more in Europe and within a smaller consortium in North America.”

In addition, he said, “as we begin to increase use of immunotherapy within our chemotherapy backbones, we need to understand the relationship these drugs have with asparaginase treatment.”

Dr. Burke and Dr. Wistinghausen have no disclosures. Dr. Maese discloses relationships with Jazz (advisory board, consultant, speakers bureau) and Servier (advisory board).

The chemotherapy drug asparaginase revolutionized childhood cancer care in the 1970s, and it’s still a mainstay of treatment for acute lymphoblastic leukemia (ALL) today. But asparaginase remains difficult for some to tolerate, and clinicians keep needing to adjust therapy to address toxicity.

The good news, hematologists note, is that new strategies have been developed to address side effects. “We’ve gotten better at managing them,” pediatric oncologist Birte Wistinghausen, MD, of Children’s National Hospital in Washington, DC, said in an interview.

According to her, key approaches include sensitivity testing and “pre-medication” to prevent adverse effects from appearing in the first place.

The American Cancer Society estimates that 6,550 new cases of ALL appear in the United States each year, and 1,330 people die from the disease.

“Most cases of ALL occur in children, but most deaths from ALL (about 4 out of 5) occur in adults,” the organization reports. Indeed, the 5-year survival rate in children is now at about 90%, a number that hematologists partially attribute to the power of asparaginase.

Researchers believe that asparaginase, an enzyme, works by breaking down a substance called asparagine, which ALL cells use to reproduce. The drug is “universally used throughout the treatment of ALL in children and adolescents,” Luke Maese, DO, associate professor of pediatrics at the University of Utah–Huntsman Cancer Institute, Salt Lake City, and director of Leukemia/Lymphoma at Primary Children’s Hospital, said in an interview. “It has become more and more adopted in the treatment of young adults as well.”

The formulations of available asparaginase have evolved over the years, Dr. Maese said. “Currently, the first-line asparaginase products delivered in the majority of patients throughout the world are pegylated, meaning they have an extended duration of action. There are non-pegylated asparaginase products that are used as well.”

The pegylated drugs are much easier on patients since they don’t require frequent injections, according to experts.

Treatment protocols vary, Dr. Maese said. “Some use the drug intermittently intermixed throughout therapy, and others have periods of continuous asparaginase use — i.e. 10-20 weeks of repeated doses of the drug.”

All patients are likely to experience side effects, he said, and about 5%-10% of standard-risk and 20%-25% of high-risk patients will experience clinically significant problems.

When asparaginase is given by IV, its rapid onset can lead to a condition called acute hyperammonemia, in which ammonia levels rise and patients develop flushing, anxiety, and low blood pressure, said Dr. Wistinghausen of Children’s National Hospital. “But that is not a reason to abandon asparaginase.”

It can be difficult to differentiate this effect from hypersensitivity — allergic reactions — which can range from hives to full anaphylactic shock that requires treatment with epinephrine, she said.

According to Dr. Maese, other major side effects other than hypersensitivity include pancreatitis, hepatotoxicity, and thrombosis. The most dangerous of these side effects are hypersensitivity and pancreatitis, which can lead to discontinuation of treatment, he said. Indeed, a 2017 study found that 2% of 465 patients with ALL who developed asparaginase-associated pancreatitis died, and 8% needed mechanical ventilation.

There’s no way to predict which patients may be susceptible to pancreatitis, Michael J. Burke, MD, professor of pediatrics and director of leukemia/lymphoma director at Children’s Wisconsin and Medical College of Wisconsin, said in an interview.

As for therapy options if pancreatitis develops, a 2022 review cowritten by Dr. Maese reported that clinicians have been leaning toward re-treating patients with asparaginase since it’s so crucial to treatment. This has worked about 50% of the time, the review reported, and “many groups consider it in the setting of all grade 2 pancreatitis and grade 3 pancreatitis without prolonged illness or severe complications.”

As for hypersensitivity, the most prevalent adverse effect, clinicians frequently administer anti-allergy medications prior to infusion. This approach, known as “pre-medication,” is controversial. Research has produced conflicting results, with a 2022 study in the journal Blood finding that pre-medication had no effect on hypersensitivity in children with ALL.

“Although there is mixed data, most institutions utilize this,” Dr. Maese said. “At our institution, we continue to use pre-medication prior to pegylated asparaginase but do not use it with non-pegylated asparaginase.”

Specifically, most institutions administer H2 and H1 blockers, Dr. Wistinghausen said. “Some institutions also use hydrocortisone” — a steroid — “but our institution only uses it if patients have a reaction.”

Other potential adverse effects to treatment include infusion reactions, which can mimic allergic reactions such as nausea, vomiting, abdominal pain, and flushing, Dr. Maese said.

Asked how to treat patients who cannot tolerate first-line treatment with asparaginase, Dr. Burke responded, “There are second-generation asparaginase formulations for once a patient develops an allergy.”

Dr. Maese said his institution switches patients when necessary to asparaginase Erwinia chrysanthemi (recombinant)-rywn, also known as Rylaze.

Another recent development in ALL treatment is the widespread use of drug monitoring to make sure asparaginase is reaching therapeutic levels. “Asparagine itself is difficult to measure so we use a surrogate of asparaginase levels to demonstrate efficacy of the drug,” he said. “There is conflicting literature as to what constitutes a therapeutic level, but the internationally accepted standard is a level of ≥ 0.1 IU/mL. We monitor asparaginase levels routinely with pegylated asparaginase but not with non-pegylated asparaginase.”

Tests can turn up “silent inactivation,” a term that refers to when the drug is “inactivated” and is not effective, Dr. Maese said. “There are several guidelines that have defined inactivation.” According to the 2022 report cowritten by Dr. Maese, Rylaze can be an alternative option if initial asparaginase treatment isn’t working.

With regard to cost, treatment with asparaginase can cost tens of thousands of dollars. However, insurers routinely pay for treatment plus pre-medication and testing, Dr. Burke said. “There’s no pushback. It seems to be accepted.”

What’s next on the horizon? “We need to understand better those patients who are at risk for toxicity,” Dr. Maese noted. “We understand obesity causes risk for certain toxicities, but have little else to go on. There has been some work with genomics and its relationship to risk of toxicity. However, it has been difficult to translate what has been found to patients.”

There’s work in progress that is exploring other preventive approaches to decrease toxicity, he said. Also, “optimizing the dosing of asparaginase has been explored more in Europe and within a smaller consortium in North America.”

In addition, he said, “as we begin to increase use of immunotherapy within our chemotherapy backbones, we need to understand the relationship these drugs have with asparaginase treatment.”

Dr. Burke and Dr. Wistinghausen have no disclosures. Dr. Maese discloses relationships with Jazz (advisory board, consultant, speakers bureau) and Servier (advisory board).

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

Age older than 65 years and serum creatinine greater than 140 micromol/L at the time of systemic polyarteritis nodosa (PAN) diagnosis were significant predictors of mortality.

METHODOLOGY:

• A total of 358 patients diagnosed with PAN between 1990 and 2020 were identified from retrospective chart reviews and prospective cohorts from nine countries as a part of GLOBAL-PAN, a collaboration of the European Vasculitis Society, the Vasculitis Clinical Research Consortium, and other networks.
• The goal of the retrospective chart review was to characterize the nature, presentation, and survival rates of patients with PAN.
• The study population included 174 female and 184 male patients; 282 had systemic PAN (sPAN) and 76 had cutaneous PAN (cPAN); the mean age at diagnosis was 44.3 years.

TAKEAWAY:

• Overall survival rates at 1, 5, and 10 years for patients with sPAN were 97.1%, 94.0%, and 89.0%, respectively.
• Significant independent predictors of mortality were age ≥ 65 years at the time of sPAN diagnosis (hazard ratio [HR], 3.85), serum creatinine > 140 micromol/L at the time of diagnosis (HR, 4.93), gastrointestinal involvement (HR, 3.51), and central nervous system involvement (HR, 3.56).
• Constitutional symptoms were significantly more common in patients with sPAN vs cPAN (78.8% vs 44.7%), while patients with cPAN were significantly more likely to be female and have more skin nodules than patients with sPAN.
• Relapse over a median disease duration of 59.6 months was slightly higher for cPAN vs sPAN (38.8% vs 32.1%).

IN PRACTICE:

“This study helps better define the demographic and clinical characteristics of patients with PAN and differentiates sPAN from cPAN,” the researchers wrote.

SOURCE:

The lead author of the study was Omer Karadag, MD, of Hacettepe University, Ankara, Turkey. The study was published online on February 12 in Arthritis & Rheumatology.

LIMITATIONS:

Study limitations included the combination of prospective and retrospective data, varying approaches to patient assessment, and lack of data on treatment effects.

DISCLOSURES:

The study was supported by the Vasculitis Clinical Research Consortium, which received funding from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. Dr. Karadag disclosed research grants from AbbVie, Novartis, Viela-Bio, and TR-Pharma, and consulting fees from AbbVie, Abdi Ibrahim, Celltrion, Novartis, Pfizer, Sandoz, and UCB.

A version of this article appeared on Medscape.com.

NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.

Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).

Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.

At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.

In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.

The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.

Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.

The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.

Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.

The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
 

More Options Empower Mothers

Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.

The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.

“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”

The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
 

Study Supports Safety of Conservative Management

“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.

“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.

Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.

As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.

The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.

Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).

Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.

At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.

In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.

The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.

Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.

The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.

Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.

The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
 

More Options Empower Mothers

Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.

The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.

“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”

The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
 

Study Supports Safety of Conservative Management

“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.

“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.

Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.

As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.

The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Rates of maternal morbidity in individuals with placenta accreta were similar with alternative strategies to cesarean hysterectomy regardless of the severity of the condition, based on data from 60 individuals.

Currently, the recommended management strategy for placenta accreta spectrum (PAS) is a cesarean hysterectomy, but data are lacking on alternative strategies, especially for individuals wishing to keep their uterus and potentially preserve fertility, Farah H. Amro, MD, of the University of Texas Health Science Center at Houston McGovern Medical School said in a presentation at the Pregnancy Meeting (abstract 70).

Alternative options are being studied worldwide, including delayed hysterectomy (typically performed at 4-6 weeks postpartum), Dr. Amro said at the meeting, which was sponsored by the Society for Maternal-Fetal Medicine.

At UT Houston, delayed hysterectomy is performed for more aggressive PAS that involves parametrial invasion, and the placenta left in situ until resorption/passage for those wishing to keep their uterus, Dr. Amro said in an interview.

In a cohort study at UT Houston, a level IV academic center, Dr. Amro and colleagues evaluated outcomes in 60 individuals with suspected PAS who were given three management options after extensive counseling. Of these, 29 opted for a cesarean hysterectomy (CH); 16 opted for delayed interval hysterectomy (IH) performed 4-6 weeks after delivery; and 15 individuals with a preference for uterine preservation were assigned to conservative management.

The study occurred between January 2020 and July 2023. The primary outcome was composite maternal morbidity, which was further divided into composite acute morbidity (within 24 hours from cesarean delivery or hysterectomy) and composite delayed morbidity (24 hours or more postoperatively). Secondary outcomes included total estimated blood loss, need for blood transfusion, unplanned hospital readmission, and pathology diagnosis.

Overall maternal morbidity rates were 55%, 56%, and 53% in the CH, IH, and CM groups, respectively, although those who were planned for IH and CM had more severe PAS.

The planned procedure was performed in 90% of the CH patients. Approximately 20% of patients in the IH and CM groups underwent unplanned procedures. No cases of sepsis or maternal death occurred, and uterine infection rates were 0%, 6%, and 13% in the CH, IH, and CM groups, respectively.

Patients in the CM and IH groups were significantly less likely to require blood transfusions than those in the CH group. In addition, composite delayed morbidity (24 hours or more after surgery) was similar among the groups, with rates of 31%, 38%, and 33% for CH, IH, and CM, respectively (P = .94). These results are important, given the concerns regarding leaving a placenta in situ after cesarean delivery, said Dr. Amro.

The findings were limited by several factors including the use of data from a single site, the lack of randomization, patient compliance, and cost effectiveness. However, the results were strengthened by the diverse population and comparison of novel approaches that aren’t frequently utilized In the United States, as well as the large volume of PAS cases treated in a relatively short time frame, Dr. Amro said.
 

More Options Empower Mothers

Overall, the results support the use of delayed hysterectomy and conservative management as safe alternatives to cesarean hysterectomy, especially in those with severe PAS (opting for IH Instead of CH) and those seeking to preserve the uterus (CM), Dr. Amro said. However, these alternative options can be offered only to patients who can engage in frequent postpartum follow-up and live close to the hospital; with the CM group, resorption/passage of the placenta may take as long as 6 months in some cases, she explained.

The greatest concerns with leaving the placenta in place in PAS patients are the risk of infection or subsequent hemorrhage, Dr. Amro said in an interview. However, the current study showed that the infection rate was not as high as anticipated, and the frequency of unplanned procedures occurred in only 20%, which should alleviate some of these concerns, she said.

“We have completed 28 cases of conservative management since 2015, four have gone on to successful pregnancy with no cases of PAS in the subsequent pregnancies,” Dr. Amro said. Conservative management gives mothers another option, she added. “Moms feel empowered by being given a choice, especially for those that want to keep their uterus for fertility or religious/cultural considerations, and many opt for CM.”

The next step is to take the conservative management strategy to larger groups at other centers to replicate the results in other locations, said Dr. Amro. “Also, we are looking at the utility of other interventions such as uterine artery embolization and performing delayed dilation and curettage to help with passage of the placenta in those opting for CM.”
 

Study Supports Safety of Conservative Management

“There are patients that may want to preserve their reproductive organs in the face of an accreta (such as for religious, cultural, and personal reasons), and this study helps address some of the safety considerations with conservative approaches,” Corrina M. Oxford-Horrey, MD, a maternal-fetal medicine specialist at Weill Cornell Medicine, New York, said in an interview.

“I was surprised that there was not a lot of infectious morbidity (such as sepsis) in the cohorts; that was helpful to see,” said Dr. Oxford-Horrey, who served as a moderator for the session in which the study was presented.

Based on the study findings, “nontraditional approaches to placenta accreta spectrum management may be reasonable, given similar overall postoperative composite morbidity between the groups,” she said.

As for additional research, replicating the study in a multicenter fashion would add to the generalizability of the findings, Dr. Oxford-Horrey said.

The study received no outside funding. The researchers and Dr. Oxford-Horrey had no financial conflicts to disclose.