Conference Coverage

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Promising early results from an ongoing randomized, open-label, single-arm, phase 3 study could pave the way for a Pfizer product to become the second US Food and Drug Administration (FDA)–approved gene therapy for hemophilia A.

In an efficacy population of 50 patients with hemophilia A, the AFFINE trial found that their mean annualized bleeding rate (ABR) fell from 4.73 pre-infusion with giroctocogene fitelparvovec to 1.24 post-infusion (week 12 to 15 or more months, −3.49, −6.06 to −0.91; P = .004), researchers reported earlier this month at American Society of Hematology (ASH) 2024 Annual Meeting. Sixty-four percent had no bleeding events over a median follow-up of 33.6 months (14.5-44.4).

The ABR for treated bleeds fell from 4.08 to 0.07 (−4.01, −5.57 to −2.45; P < .0001), and 88% had no treated bleeds over the same follow-up period.

“The primary endpoint for this trial was a reduction in total bleeds in patients, and that was achieved,” hematologist and first author Andrew D. Leavitt, MD, of the University of California at San Francisco, said in an interview. “More impressive was the reduction in treated bleeds, a kind of a surrogate marker for bleeds of clinical significance to the individual. And as one would expect or hope to see in a gene therapy trial, there was a significant and marked reduction in the use of factor.”

Moving forward, he said, the message to clinicians is that “there’s every reason to believe that they will have yet another option for their patients.”

Gene Therapy on the Rise in Hemophilia 

Gene therapy has arisen as an approved therapy for hemophilia over just the last few years. Two gene therapies for hemophilia B have been approved by the FDA since 2022, and one was approved for hemophilia A, the more common type, in 2023.

As Leavitt noted, one-time treatment with gene therapy offers an alternative to treatment with blood factor, long the mainstay of hemophilia therapy.

“One of the real pluses of gene therapy is the potential to remove the burden of hemophilia, which is large and, I suspect, underappreciated even by providers,” he said. “You have to sit down with your patients and really get a real good sense of just how difficult it is for them to manage with many products on the market over the last few decades.”

Why is there a need for multiple gene therapy products? “A patient may have neutralizing antibodies against the proteins on the surface of gene therapy product A that prevents its use, but not on gene therapy B, which allows use of product B,” Leavitt said. “We need a few flavors so that we can offer gene therapy to the maximum number of interested patients.”

High Efficacy and an ‘Acceptable’ Safety Profile

For the study, researchers dosed 75 patients (mean age, 32.3 [19-59]; 100% men, 74.7% White and 18.7% Asian,) with hemophilia A with giroctocogene fitelparvovec, a hepatocyte-directed recombinant adeno-associated virus serotype 6 vector encoding a B-domain–deleted variant of human factor VIII. The efficacy population is 50 patients with at least 6 months of follow-up in the lead-in study.

The annualized infusion rate of exogenous FVIII was 124.39 mean annualized infusion rate prior to the treatment infusion vs 0.21 post-infusion, week 12 through at least 15 months (−124.18, −139.47 to −108.89; P < .0001).

Leavitt said the results are similar to other gene therapies for hemophilia in that “it is difficult to predict how high your factor level will become. There’s a broad range of outcomes for individuals, and the duration of expression remains an unknown.”

The study authors described the treatment as “generally well tolerated” with “an acceptable and manageable safety profile.”

Of the 75 subjects, 98.7% had adverse effects (AEs, 740 events) and 90.7% had treatment-related AEs. Common treatment-related AEs included hepatotoxicity (62.7%) and infusion-related reactions (73.3%). No subjects discontinued therapy due to AEs.

Nearly two thirds — 62.7% — of subjects used corticosteroids for a mean 114.6 days (11-296).

Study Findings ‘Look Really Good’

In an interview, Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles and professor of pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, said that “generally speaking, the new data looks really good.” Young, who didn’t take part in the study, noted that factor levels following treatment were high, and one subject actually had a thrombotic event and needed to be treated with an anticoagulant.

The high factor levels could actually be a sign of lasting benefit vs valoctocogene roxaparvovec (Roctavian), the sole FDA-approved gene therapy for hemophilia A, which is linked to significant drops in factor level after 6 months, he said. “Wouldn’t it be better to start really high?”

Gene therapy for hemophilia is highly expensive, although proponents noted that insurers may save money over the long run if patients don’t require prophylactic treatment or therapy for bleeds.

A Pfizer spokesman declined to comment on the new therapy’s potential cost. In regard to when the therapy may receive FDA approval, he said “Pfizer is discussing this data with regulatory authorities.”

Pfizer funded this study. Leavitt disclosed ties with HEMA, Merck, Catalyst, Genentech, Pfizer, BioMarin, and Sangamo. Other study authors reported relationships with Pfizer. Young disclosed ties with Pfizer and BioMarin.

 

A version of this article appeared on Medscape.com.

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

Identifying the phenomenon of post-exertional malaise (PEM) in patients with fatiguing conditions is critical because it necessitates a far more cautious approach to exercise, experts said.

PEM is a defining feature of the condition myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and it is present in many people with long COVID. It is characterized by a worsening of fatigue and of other symptoms after previously tolerated physical or mental exertion, typically emerging 24-72 hours after the exertion and lasting days or weeks thereafter. The experience is often called a “crash.”

In a study presented at the American College of Rheumatology (ACR) 2024 Annual Meeting, PEM was also identified in people with various rheumatologic conditions, ranging from 4% in those with osteoarthritis to 20% in those with fibromyalgia. The presence of PEM was also associated with worse pain, sleep, cognition, and other symptoms that are also characteristic of ME/CFS and many cases of long COVID.

“PEM assessment is becoming more important in those with long COVID, as we are assisting more of those with long durations of this condition. ... This is the first study we know of presenting PEM rates in a rheumatologic disease population,” Kaleb Michaud, PhD, director of FORWARD — The National Databank for Rheumatic Diseases and professor of rheumatology and immunology, University of Nebraska Medical Center, Omaha, said at the meeting.

During the discussion period, study investigator Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Ohio, commented, “PEM is seen with numerous post-acute infectious sequelae. It segregates with that population of patients who meet the diagnostic criteria for ME/CFS, of which 50%-70% of people will also meet criteria for fibromyalgia…This is a first step, but it has big ramifications regarding exercise.”

In an interview with this news organization, Calabrese said, “We recommend exercise to virtually everyone with fibromyalgia who doesn’t have ME/CFS,” but that the assessment tool used in the study, the 5-item DePaul Symptoms Questionnaire, isn’t adequate for assessing true PEM that would preclude exercise, despite being validated. “That instrument is inexact and lacks specificity. ... It just shows where the field is. We need better biomarkers.”

 

In Those With PEM, Exercise May Harm

Asked to comment, Brayden P. Yellman, MD, a rheumatologist at the Bateman Horne Center, Salt Lake City, Utah, told this news organization, “if there is an infection-associated chronic condition that meets criteria for what we would call ME/CFS or long COVID, and if there’s true post-exertional malaise, any graded exercise that ultimately leads to post-exertional malaise is harmful. ... There is a subset of people who have milder disease, who can sometimes do very mild exercise that does not trigger PEM, and they do see benefits over time very slowly with really carefully curated, carefully monitored exercise. But we have to be really careful.”

For the majority, however, the approach is to teach patients to pace their activities in order to avoid PEM, also referred to as staying within their “energy envelope.” Clinician resources are available on the Bateman Horne Center’s website.

This isn’t typically included in rheumatology training, Yellman noted. “Having completed an entire rheumatology fellowship and working in rheumatology, I was not taught at all about [then-termed] chronic fatigue syndrome. It was lumped under fibromyalgia. And of course, they teach about fibromyalgia because it’s a great mimic of a lot of inflammatory, rheumatologic conditions, but the idea of [PEM], that pathognomonic feature that we see in infection-associated chronic conditions, was not once mentioned when I trained, in 2014 to 2016.”

Nonetheless, he added, “rheumatologists are definitely seeing this in their fibromyalgia patients and some of their other patients at a high rate, and I’m sure that they’re missing it, along with other comorbidities like orthostatic hypotension.”

Another expert asked to weigh in, Todd Davenport, PT, DPT, PhD, professor and chair of the Department of Physical Therapy at the University of the Pacific, Stockton, California, told this news organization: “Our experience is that the body’s responses to short bouts of exercise are abnormal, and graded exercise is unsuccessful and makes people worse. ... Clinicians should be particularly on the lookout for PEM in patients who are already reporting fatigue, such as with fibromyalgia and rheumatologic conditions that can have some diagnostic overlaps with ME/CFS, because you can get fooled into thinking that your well-meaning exercise program intended to help give them a little more juice during their daily activities actually might be harmful.”

There are several lines of evidence for abnormal responses to exercise in people with PEM, Davenport said. These include muscle worsening, cardiac preload failure and impaired systemic oxygen extraction, metabolic dysregulation, and abnormal immunologic and neurologic changes.

Several studies show impaired recovery after 2-day cardiopulmonary exercise testing, with the largest to date published in July 2024. Patients with PEM have also reported harm from prescribed exercise.

Yellman commented: “We think of PEM like an injury, where you need to recover. If you keep stacking injuries on top of it, that injury is never going to heal the same way again…We are still trying to understand the pathophysiology of ME/CFS in general, and of PEM. But if you think of it as a neuroinflammatory injury, and there’s some evidence suggesting neuroinflammation, you can kind of understand the approach of needing to heal and to recover.”

 

How Prevalent Is PEM in Rheumatologic Conditions?

For the study presented at the ACR meeting, data of people with confirmed rheumatic diseases were taken from the ongoing longitudinal US-based research database FORWARD. Participants completed biannual self-reported questionnaires during January–June 2024 that included the 5-item PEM subscale from the validated DePaul Symptoms Questionnaire.

Questions relate to frequency and severity of each of the five items: “Dead, heavy feeling after starting to exercise,” “next-day soreness or fatigue after nonstrenuous, everyday activities,” “mentally tired after the slightest effort,” “minimum exercise makes you physically tired,” and “physically drained or sick after mild activity.” Participants are asked to rate each item on a scale from 0 if not present to 1 (mild/a little of the time) up to 4 (very severe/all of the time).

A positive PEM result was defined as a frequency of at least two and simultaneous severity of at least two on any survey item. Additional questions asked about recent and previous SARS-CoV-2 infections, long COVID diagnoses, and comorbidities.

Of 1158 individuals who completed the PEM questionnaire, 7.5% overall met PEM criteria. By individual condition, the proportions were 4.4% with osteoarthritis, 7.4% with rheumatoid arthritis, 12.2% with systemic lupus erythematosus, 13.8% with fibromyalgia diagnosed by rheumatologists, and 20.3% with fibromyalgia based on the 2016 revised ACR criteria.

The overall PEM prevalence was 8.3% among those reporting ever having COVID-19 and 9.5% among those who had COVID-19 during July–December 2023. The PEM prevalence increased more dramatically with more severe COVID-19 — 17.2% among those who had been hospitalized for COVID-19, 22.0% of those ever diagnosed with long COVID, and 28.1% with a long COVID diagnosis in January 2024.

By diagnosis, 50% of individuals who met the ACR’s 2016 fibromyalgia criteria and currently had long COVID scored positively for PEM.

Measures of pain, fatigue, sleep, patient global assessment, activity score, polysymptomatic distress, disability, depression, anxiety, and other functional scores were all significantly worse among those scoring positive for PEM (P < .001), Michaud reported.

 

Better Tools Are Available

The developer of the DePaul questionnaire, Leonard Jason, PhD, director of the Center for Community Research and professor of psychology at DePaul College of Science and Health, Chicago, Illinois, told this news organization that an updated 10-item screening tool specifically designed to screen for PEM adds some important elements missing from the 5-item version.

Here, patients are initially asked two questions: “Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?” and “Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?” If they answer “yes” to either, the next question is “If you feel worse after activities, how long does this last?” Answers are coded from 0 to 6 (24 hours or more).

The fourth additional question then asks how quickly patients recover, while a fifth question asks whether the person is avoiding activity because it makes them feel worse (thereby potentially creating a false negative).

For those scoring positive on the 10-item screen, a more comprehensive measure could be used, such as this online screening tool, Jason said.

Yellman said that the Bateman Horne Center uses a “good day, bad day” questionnaire to tease out some of the same information. In addition, he noted that it’s important to capture the timeframe between the exertion and the onset of symptoms because PEM doesn’t start during or immediately after activity. “If somebody is mowing the lawn and they start feeling symptoms immediately, they’re probably, at least in ME/CFS, experiencing orthostatic intolerance. Post-exertional malaise occurs 12-72 hours later, when their function is severely reduced as compared to baseline.” 

And of course, Davenport noted, listening to patients is key. “Patients will tell you wildly unusual responses to activity before you even do the work of trying to figure out what the activity was. They’ll tell you things like they can’t think as well, that they have to be in bed for 3 days to a week to 2 weeks, depending on the level of exertion.”

Yellman, Davenport, and several other colleagues are currently working on a paper that will explain the differences between pacing and graded exercise, define PEM, and provide guidelines. They aim to submit it in time for publication early in 2025. In the meantime, the Bateman Horne Center’s website provides numerous resources for healthcare professionals and patients.

Yellman is also working to define minimum quality of care standards for infection-associated chronic conditions for state medical boards and to provide continuing medical education for clinicians on those standards. These would include recognizing and evaluating patients for PEM, as well as orthostatic intolerance, cognitive impairment, and other associated comorbidities.

Importantly, he said, the standards will include the principles of teaching people with PEM how to pace and will emphasize not prescribing them graded exercise as first- or even second-line therapy. “We need people to do some basic things. And the first thing is do no harm.”

None of the individuals quoted for this article had relevant financial disclosures.

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

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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