Over the past two decades, the therapeutic landscape for psoriatic arthritis (PsA) has been transformed by the introduction of more than a dozen targeted therapies.

For most patients with active PsA, a tumor necrosis factor (TNF) inhibitor is recommended as the first-line biologic therapy. But some patients do not achieve an adequate response to TNF inhibitors or are intolerant to these therapies.

Choosing the right treatment after failure of the first biologic requires that clinicians consider several factors. Dr Atul Deodhar, of Oregon Health & Science University, discusses guidelines from the American College of Rheumatology/National Psoriasis Foundation and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) for appropriate treatment strategies.

He also discusses factors critical to the optimal choice of the next therapy, such as the domains of disease activity, patient comorbidities, and whether the biologic's failure was primary or secondary.

Aside from choosing a new biologic, Dr Deodhar notes that there are other options to intensify the effect of the initial biologic. He says the clinician and patient may consider increasing the dose and frequency of the initial biologic medication or moving to a combination therapy by adding another drug, such as methotrexate.

--

Atul A. Deodhar, MD, Professor of Medicine, Division of Arthritis and Rheumatic Diseases, School of Medicine, Oregon Health & Science University; Medical Director, Rheumatology Clinics, OHSU Hospital, Portland, Oregon

Atul A. Deodhar, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant, for: Bristol Myers Squibb; Eli Lilly; Janssen; MoonLake; Novartis; Pfizer; UCB

Serve(d) as a speaker for: Eli Lilly; Novartis; Pfizer; UCB

Received research grant from: AbbVie; Bristol Myers Squibb; Celgene; Janssen; MoonLake; Novartis; Pfizer; UCB

Received income in an amount equal to or greater than $250 from: Bristol Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; Samsung Bioepis; UCB

Over the past two decades, the therapeutic landscape for psoriatic arthritis (PsA) has been transformed by the introduction of more than a dozen targeted therapies.

For most patients with active PsA, a tumor necrosis factor (TNF) inhibitor is recommended as the first-line biologic therapy. But some patients do not achieve an adequate response to TNF inhibitors or are intolerant to these therapies.

Choosing the right treatment after failure of the first biologic requires that clinicians consider several factors. Dr Atul Deodhar, of Oregon Health & Science University, discusses guidelines from the American College of Rheumatology/National Psoriasis Foundation and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) for appropriate treatment strategies.

He also discusses factors critical to the optimal choice of the next therapy, such as the domains of disease activity, patient comorbidities, and whether the biologic's failure was primary or secondary.

Aside from choosing a new biologic, Dr Deodhar notes that there are other options to intensify the effect of the initial biologic. He says the clinician and patient may consider increasing the dose and frequency of the initial biologic medication or moving to a combination therapy by adding another drug, such as methotrexate.

--

Atul A. Deodhar, MD, Professor of Medicine, Division of Arthritis and Rheumatic Diseases, School of Medicine, Oregon Health & Science University; Medical Director, Rheumatology Clinics, OHSU Hospital, Portland, Oregon

Atul A. Deodhar, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant, for: Bristol Myers Squibb; Eli Lilly; Janssen; MoonLake; Novartis; Pfizer; UCB

Serve(d) as a speaker for: Eli Lilly; Novartis; Pfizer; UCB

Received research grant from: AbbVie; Bristol Myers Squibb; Celgene; Janssen; MoonLake; Novartis; Pfizer; UCB

Received income in an amount equal to or greater than $250 from: Bristol Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; Samsung Bioepis; UCB

Over the past two decades, the therapeutic landscape for psoriatic arthritis (PsA) has been transformed by the introduction of more than a dozen targeted therapies.

For most patients with active PsA, a tumor necrosis factor (TNF) inhibitor is recommended as the first-line biologic therapy. But some patients do not achieve an adequate response to TNF inhibitors or are intolerant to these therapies.

Choosing the right treatment after failure of the first biologic requires that clinicians consider several factors. Dr Atul Deodhar, of Oregon Health & Science University, discusses guidelines from the American College of Rheumatology/National Psoriasis Foundation and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) for appropriate treatment strategies.

He also discusses factors critical to the optimal choice of the next therapy, such as the domains of disease activity, patient comorbidities, and whether the biologic's failure was primary or secondary.

Aside from choosing a new biologic, Dr Deodhar notes that there are other options to intensify the effect of the initial biologic. He says the clinician and patient may consider increasing the dose and frequency of the initial biologic medication or moving to a combination therapy by adding another drug, such as methotrexate.

--

Atul A. Deodhar, MD, Professor of Medicine, Division of Arthritis and Rheumatic Diseases, School of Medicine, Oregon Health & Science University; Medical Director, Rheumatology Clinics, OHSU Hospital, Portland, Oregon

Atul A. Deodhar, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant, for: Bristol Myers Squibb; Eli Lilly; Janssen; MoonLake; Novartis; Pfizer; UCB

Serve(d) as a speaker for: Eli Lilly; Novartis; Pfizer; UCB

Received research grant from: AbbVie; Bristol Myers Squibb; Celgene; Janssen; MoonLake; Novartis; Pfizer; UCB

Received income in an amount equal to or greater than $250 from: Bristol Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; Samsung Bioepis; UCB

Bipolar 1 disorder is a chronic and disabling mental health disorder that results in cognitive, functional, and social impairments associated with an increased risk for hospitalization and premature death.

Bipolar 1 disorder is characterized by manic episodes that last for at least 7 days, or manic symptoms that are so severe that they require immediate medical care. Depressive episodes also occur.

Dr Michael Thase, from the University of Pennsylvania, explains that although ongoing treatment is essential to prevent relapse and recurrence, particularly after a hospitalization, adherence can be serious problem.

Long-acting injectable (LAI) agents can act as a bridge between oral medications initiated in hospital and ongoing prevention therapies.

Dr Thase says LAIs can help improve adherence and patient quality of life, and are effective against relapses in adults with bipolar 1 disorder.

--

Michael E. Thase, MD, Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Michael E. Thase, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc; Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; Biohaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuticals; Seelos Therapeutics; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd

Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; Biohaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd

Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W.W. Norton & Company, Inc

Bipolar 1 disorder is a chronic and disabling mental health disorder that results in cognitive, functional, and social impairments associated with an increased risk for hospitalization and premature death.

Bipolar 1 disorder is characterized by manic episodes that last for at least 7 days, or manic symptoms that are so severe that they require immediate medical care. Depressive episodes also occur.

Dr Michael Thase, from the University of Pennsylvania, explains that although ongoing treatment is essential to prevent relapse and recurrence, particularly after a hospitalization, adherence can be serious problem.

Long-acting injectable (LAI) agents can act as a bridge between oral medications initiated in hospital and ongoing prevention therapies.

Dr Thase says LAIs can help improve adherence and patient quality of life, and are effective against relapses in adults with bipolar 1 disorder.

--

Michael E. Thase, MD, Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Michael E. Thase, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc; Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; Biohaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuticals; Seelos Therapeutics; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd

Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; Biohaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd

Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W.W. Norton & Company, Inc

Bipolar 1 disorder is a chronic and disabling mental health disorder that results in cognitive, functional, and social impairments associated with an increased risk for hospitalization and premature death.

Bipolar 1 disorder is characterized by manic episodes that last for at least 7 days, or manic symptoms that are so severe that they require immediate medical care. Depressive episodes also occur.

Dr Michael Thase, from the University of Pennsylvania, explains that although ongoing treatment is essential to prevent relapse and recurrence, particularly after a hospitalization, adherence can be serious problem.

Long-acting injectable (LAI) agents can act as a bridge between oral medications initiated in hospital and ongoing prevention therapies.

Dr Thase says LAIs can help improve adherence and patient quality of life, and are effective against relapses in adults with bipolar 1 disorder.

--

Michael E. Thase, MD, Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Michael E. Thase, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Acadia, Inc; Akili, Inc; Alkermes PLC; Allergan, Inc; Axsome Therapeutics, Inc; Biohaven, Inc; Bocemtium Consulting, SL; Boehringer Ingelheim International; CatalYm GmbH; Clexio Biosciences; Gerson Lehrman Group, Inc; H Lundbeck, A/S; Jazz Pharmaceuticals; Janssen; Johnson & Johnson; Luye Pharma Group, Ltd; Merck & Company, Inc; Otsuka Pharmaceuticals Company, Ltd; Pfizer, Inc; Sage Pharmaceuticals; Seelos Therapeutics; Sunovion Pharmaceuticals, Inc; Takeda Pharmaceutical Company, Ltd

Receive research funding from: Acadia, Inc; Allergan, Inc; AssureRx; Axsome Therapeutics, Inc; Biohaven, Inc; Intracellular, Inc; Johnson & Johnson; Otsuka Pharmaceuticals Company, Ltd; Patient-Centered Outcomes Research Institute (PCORI); Takeda Pharmaceutical Company, Ltd

Receive royalties from: American Psychiatric Foundation; Guilford Publications; Herald House; Kluwer-Wolters; W.W. Norton & Company, Inc

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

For Courtney Stinson, ensuring her daughter’s comfort is a constant battle against the challenges of congenital myopathy. At 9 years old, she relies on a ventilator to breathe, has multiple respiratory treatments daily, and is under the constant care of rotating skilled caregivers. Last year alone, she endured 36 doctor appointments.

To ease her daughter’s struggles with sleep, and after consulting a pediatrician, Ms. Stinson turned to melatonin, a hormone naturally produced by the body to manage sleep. She gave her daughter a low dose of melatonin and saw significant improvement in her ability to settle down, especially when her mind raced.

“She would have such a hard time sleeping when everything is swirling in her head,” said Ms. Stinson, a mother of two who lives in Milan, Michigan. “It’s really been helpful when her brain is moving 100 miles an hour.”

Melatonin is sold without a prescription as a sleep aid in the form of a supplement. For some parents, especially those whose children have complex needs, melatonin can be a valuable resource — but the rise in melatonin across otherwise healthy populations has had its consequences, too, according to pediatric sleep experts. 

Recent data from the CDC illustrates one of these drawbacks: a significant surge in accidental melatonin ingestion among young children over the past 2 decades.

Between 2012 and 2021, poison center calls related to pediatric melatonin exposures skyrocketed by 530%, while emergency department visits for unsupervised melatonin ingestion by infants and young children surged by 420% from 2009 to 2020, according to the CDC report.

Between 2019 and 2022, an estimated 10,930 emergency room visits were linked to 295 cases of children under the age of 6 ingesting melatonin. These incidents accounted for 7.1% of all emergency department visits for medication exposures in this age group, according to the report.

The share of U.S. adults using melatonin increased from 0.4% during 1999 to 2000 to 2.1% during 2017 to 2018.

Doctors say the escalating number of melatonin-related incidents underscores the need for increased awareness and safety measures to protect young children from unintentional overdose, which can cause nausea, vomiting, diarrhea, dizziness, and confusion.

“I do think there is a safe way to use it in certain children, but it should only be used under the guidance of a physician,” said Laura Sterni, MD, director of the Johns Hopkins Pediatric Sleep Center. “There are dangers to using it without that guidance.”
 

Almost 1 in 5 Children Use Melatonin 

Nearly 1 in 5 school-age children and preteens take melatonin for sleep, according to research published last year in JAMA Pediatrics, which also found that 18% of children between 5 and 9 take the supplement.

The American Academy of Sleep Medicine issued a warning in 2022 advising parents to approach the sleep aid with caution. 

“While melatonin can be useful in treating certain sleep-wake disorders, like jet lag, there is much less evidence it can help healthy children or adults fall asleep faster,” M. Adeel Rishi, MD, vice chair of the Academy of Sleep Medicine’s Public Safety Committee, warned on the academy’s site. “Instead of turning to melatonin, parents should work on encouraging their children to develop good sleep habits, like setting a regular bedtime and wake time, having a bedtime routine, and limiting screen time as bedtime approaches.”
 

What’s the Best Way to Give Kids Melatonin?

Melatonin has been found to work well for children with attention deficit hyperactive disorder (ADHD), autism spectrum disorder, or other conditions like blindness that can hinder the development of a normal circadian rhythm. 

But beyond consulting a pediatrician, caregivers whose children are otherwise healthy should consider trying other approaches to sleep disruption first, Dr. Sterni said, and things like proper sleep hygiene and anxiety should be addressed first. 

“Most sleep problems in children really should be managed with behavioral therapy alone,” she said. “To first pull out a medication to treat that I think is the wrong approach.”

Sterni also recommends starting with the lowest dose possible, which is 0.5 milligrams, with the help of pediatrician. It should be taken 1 to 2 hours before bedtime and 2 hours after their last meal, she said. 

But she notes that because melatonin is sold as a supplement and is not regulated by the FDA, it is impossible to know the exact amount in each dose.

According to JAMA, out of 25 supplements of melatonin, most of the products contained up to 50% more melatonin than what was listed.
 

Dangers of Keeping It Within Reach 

One of the biggest dangers for children is that melatonin is often sold in the form of gummies or chewable tablets — things that appeal to children, said Jenna Wheeler, MD, a pediatric critical care doctor at Orlando Health Arnold Palmer Hospital for Children. 

Because it is sold as a supplement, there are no child-safe packaging requirements. 

“From a critical care standpoint, just remember to keep it up high, not on the nightstand or in a drawer,” Dr. Wheeler said. “A child may eat the whole bottle, thinking, ‘This is just like fruits snacks.’ ”

She noted that the amount people need is often lower than what they buy at the store, and that regardless of whether it is used in proper amounts, it is not meant to be a long-term supplement — for adults or for children.

“Like with anything that’s out there, it’s all about how it’s used,” Dr. Wheeler said. “The problem is when kids get into it accidentally or when it’s not used appropriately.”
 

A version of this article appeared on WebMD.com.

COVID-19 may be headed toward a springtime retreat. 

The indication comes from declining levels of SARS-CoV-2 being detected in wastewater over the past 3 weeks. Virus levels are already considered “low” throughout western U.S. states. Detections are at medium levels in the Midwest and South, while high levels persist in the Northeast, according to WastewaterSCAN.

But it’s not time to let your guard down because high levels of other viruses that cause stomach and respiratory illnesses continue to circulate widely nationwide. Wastewater data currently shows threats from flu, RSV, norovirus, and rotavirus.

The rate of positive flu tests reported to the CDC had been a downward trend since peaking around a rate of 16% in mid-January, but positive test rates are now climbing again, with the most recent weekly rate back around 15%. So far this flu season, 116 children and an estimated 20,000 adults have died from the flu, according to the CDC’s weekly flu publication, FluView.

RSV wastewater detection remains high, especially in the Midwest and Northeast, WastewaterSCAN data shows. But positive RSV test results reported to the CDC are at the lowest point of the 2023 to 2024 season, with less than 2,000 positive results listed for the week of March 9, down from a peak of more than 14,000 cases around Christmas.

Wastewater data tends to offer a real-time (and sometimes predictive) view of pathogen behavior in the general population, since sick people usually wait until symptoms worsen to seek medical care. About 12% of norovirus tests reported to the CDC in the last 3 weeks of February were positive, mirroring an upward trend observed during the same time period last year. In 2023, norovirus peaked in the U.S. in March with a positive test rate around 16%, CDC data show.

Last year, COVID also followed a downward springtime trend. Around this time last year, there were about 20,000 weekly hospital admissions due to COVID-19, compared to just over 13,000 in early March this year. All COVID metrics, including the positive test rate, hospitalizations, and ER visits, are currently trending downward, the CDC’s COVID Data Tracker indicates. The positive COVID test rate is 5%, and just 1% of ER visits in the U.S. involve a COVID-19 diagnosis.

“We’re seeing a downward trend, which is fantastic,” Marlene Wolfe, PhD, WastewaterSCAN’s program director, told USA Today. “Hopefully, that pattern continues as we enjoy some warmer weather and longer daylight.”
 

A version of this article appeared on WebMD.com.

COVID-19 may be headed toward a springtime retreat. 

The indication comes from declining levels of SARS-CoV-2 being detected in wastewater over the past 3 weeks. Virus levels are already considered “low” throughout western U.S. states. Detections are at medium levels in the Midwest and South, while high levels persist in the Northeast, according to WastewaterSCAN.

But it’s not time to let your guard down because high levels of other viruses that cause stomach and respiratory illnesses continue to circulate widely nationwide. Wastewater data currently shows threats from flu, RSV, norovirus, and rotavirus.

The rate of positive flu tests reported to the CDC had been a downward trend since peaking around a rate of 16% in mid-January, but positive test rates are now climbing again, with the most recent weekly rate back around 15%. So far this flu season, 116 children and an estimated 20,000 adults have died from the flu, according to the CDC’s weekly flu publication, FluView.

RSV wastewater detection remains high, especially in the Midwest and Northeast, WastewaterSCAN data shows. But positive RSV test results reported to the CDC are at the lowest point of the 2023 to 2024 season, with less than 2,000 positive results listed for the week of March 9, down from a peak of more than 14,000 cases around Christmas.

Wastewater data tends to offer a real-time (and sometimes predictive) view of pathogen behavior in the general population, since sick people usually wait until symptoms worsen to seek medical care. About 12% of norovirus tests reported to the CDC in the last 3 weeks of February were positive, mirroring an upward trend observed during the same time period last year. In 2023, norovirus peaked in the U.S. in March with a positive test rate around 16%, CDC data show.

Last year, COVID also followed a downward springtime trend. Around this time last year, there were about 20,000 weekly hospital admissions due to COVID-19, compared to just over 13,000 in early March this year. All COVID metrics, including the positive test rate, hospitalizations, and ER visits, are currently trending downward, the CDC’s COVID Data Tracker indicates. The positive COVID test rate is 5%, and just 1% of ER visits in the U.S. involve a COVID-19 diagnosis.

“We’re seeing a downward trend, which is fantastic,” Marlene Wolfe, PhD, WastewaterSCAN’s program director, told USA Today. “Hopefully, that pattern continues as we enjoy some warmer weather and longer daylight.”
 

A version of this article appeared on WebMD.com.

COVID-19 may be headed toward a springtime retreat. 

The indication comes from declining levels of SARS-CoV-2 being detected in wastewater over the past 3 weeks. Virus levels are already considered “low” throughout western U.S. states. Detections are at medium levels in the Midwest and South, while high levels persist in the Northeast, according to WastewaterSCAN.

But it’s not time to let your guard down because high levels of other viruses that cause stomach and respiratory illnesses continue to circulate widely nationwide. Wastewater data currently shows threats from flu, RSV, norovirus, and rotavirus.

The rate of positive flu tests reported to the CDC had been a downward trend since peaking around a rate of 16% in mid-January, but positive test rates are now climbing again, with the most recent weekly rate back around 15%. So far this flu season, 116 children and an estimated 20,000 adults have died from the flu, according to the CDC’s weekly flu publication, FluView.

RSV wastewater detection remains high, especially in the Midwest and Northeast, WastewaterSCAN data shows. But positive RSV test results reported to the CDC are at the lowest point of the 2023 to 2024 season, with less than 2,000 positive results listed for the week of March 9, down from a peak of more than 14,000 cases around Christmas.

Wastewater data tends to offer a real-time (and sometimes predictive) view of pathogen behavior in the general population, since sick people usually wait until symptoms worsen to seek medical care. About 12% of norovirus tests reported to the CDC in the last 3 weeks of February were positive, mirroring an upward trend observed during the same time period last year. In 2023, norovirus peaked in the U.S. in March with a positive test rate around 16%, CDC data show.

Last year, COVID also followed a downward springtime trend. Around this time last year, there were about 20,000 weekly hospital admissions due to COVID-19, compared to just over 13,000 in early March this year. All COVID metrics, including the positive test rate, hospitalizations, and ER visits, are currently trending downward, the CDC’s COVID Data Tracker indicates. The positive COVID test rate is 5%, and just 1% of ER visits in the U.S. involve a COVID-19 diagnosis.

“We’re seeing a downward trend, which is fantastic,” Marlene Wolfe, PhD, WastewaterSCAN’s program director, told USA Today. “Hopefully, that pattern continues as we enjoy some warmer weather and longer daylight.”
 

A version of this article appeared on WebMD.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

While it is increasingly apparent that clonal hematopoiesis of indeterminate potential (CHIP) is associated with conditions that can dramatically affect an individual’s risk for both malignant and cardiovascular diseases, and even death, it has not been clear what to do about it.

Now, researchers at the cutting edge of both oncologic and cardiovascular research are not only defining the prognosis of CHIP with greater granularity but are also finding clues to mitigate the risks.

“It’s a very, very rapidly moving area,” said Christie M. Ballantyne, MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, adding that, in many respects, “it’s a totally new area.”
 

CHIP Defined

CHIP was first recognized in the 1990s, when Martin F. Fey, MD, and colleagues from University and Inselspital, Bern, Switzerland, found X-linked inactivation in older women and suggested it was the result of acquired clonality later referred to as being of “indeterminate potential,” although that added syntax is currently a matter of debate.

Further work showed that, while somatic gene mutations occur spontaneously and are an unavoidable consequence of aging, their impact can vary widely.

The majority are “functionally silent,” while others may affect genes crucial to tissue self-renewal and differentiation, Lukasz Gondek, MD, PhD, assistant professor, Johns Hopkins Cellular and Molecular Medicine Program, Baltimore, and colleagues, noted in a recent review.

This results in the outgrowth of affected cells, known as clonal expansion, further dubbed clonal hematopoiesis when it occurs in hematopoietic tissue.

“Even though there’s clonal expansion, there’s no one CHIP,” Dr. Gondek said. “There are different flavors, and it depends on the genes that are mutated in the hematopoietic cells.”

He continued: “The older we get, the more mutations we acquire, and the probability that this mutation will hit the gene that’s responsible for expansion of the clone is higher.”

“That’s why CHIP is very uncommon in people under the age of 40, but it becomes more common in the fifth, sixth, and seventh decade of life and beyond.”

Indeed, it occurs in 10% to 15% of people aged 65 years or older, and in at least 30% of individuals by 80 years of age. In contrast, just 1% of those aged less than 50 years have the condition.

The most commonly affected genes, in around 80% of patients with CHIP, are the epigenetic regulators DNMT3A, TET2, and ASXL1; the DNA damage repair genes PPM1D and TP53; the regulatory tyrosine kinase JAK2; and the messenger RNA spliceosome components SF3B1 and SRSF2.

These mutations can have “two potential consequences,” explained Lachelle D. Weeks, MD, PhD, a hematologist at the Dana-Farber Cancer Institute, Boston.

“One is that there’s a risk of blood cancer development,” as several of the mutations are known drivers of leukemia or myelodysplastic syndromes (MDS).

Although the majority of individuals who acquire clonal hematopoiesis with age will never develop MDS, it nevertheless confers an 11- to 13-fold increased risk or an absolute risk of approximately 0.5%-1.0% per year.

Dr. Weeks continued that “the other side of it, though, is that those cells that have these mutations can also accelerate the risk of developing nonmalignant diseases like cardiovascular disease.”

This, Dr. Gondek explained, is because the mutations will be retained when the stem cells become monocytes or macrophages and, by either silencing or activating individual genes, they can make the cells more pro-inflammatory.

The result is that CHIP is associated with a marked increased risk for arteriosclerotic events such as stroke, myocardial infarction, decompensated heart failure, and cardiogenic shock, and worse outcomes after these events.

Researchers have shown that CHIP-related somatic mutations are associated with a twofold increased risk for coronary heart disease, a more than 2.5-fold increased risk for ischemic stroke, and a fourfold greater risk for myocardial infarction. A study from earlier this year found that CHIP also increases the risk for heart failure with preserved ejection fraction more than twofold.

There is even evidence to suggest that CHIP is associated with more severe acute kidney injury (AKI) and greater post-AKI kidney fibrosis.

The consequence is that individuals with CHIP face a 40% increased risk for all-cause mortality over 8 years.
 

No CHIP Test Yet

All of which has led for some to call for CHIP testing.

However, there are currently no screening programs for CHIP and no plans to introduce any. “So most CHIP is actually being diagnosed incidentally, when patients get genetic testing for some other indication,” said Dr. Weeks.

“The patients that we see in our CHIP clinic at Dana-Farber have genetic testing because they have low blood counts,” she continued, “and somebody’s trying to figure out: Do you have MDS?”

Other patients have genetic testing due to a family history of other cancers, “and so they’re getting hereditary cancer panels to determine if they have Lynch syndrome, or other hereditary syndromes,” which are picking up gene mutations associated with CHIP.

In other cases, study protocols are identifying CHIP “in various research contexts, and then as a follow-up, some of those patients end up with our clinic,” added Dr. Weeks.

Due to the associated risks for CHIP, “obviously everyone wants to know whether they are at risk for hematologic malignancy, or not,” said Dr. Gondek. To those ends, Dr. Weeks and colleagues developed the clonal hematopoiesis risk score (CHRS).

Published by NEJM Evidence in 2023, the score takes a range of predictive variables, such as age, number of mutations and their degree of associated risk, the variant allele fraction, and a series of blood indices to define patients as low-, intermediate-, or high-risk.

“A little over half” of high-risk individuals “will develop a blood cancer” such as MDS or acute myeloid leukemia (AML)” over the next 10 years, Weeks explained, while “for your intermediate risk folks, in that same time period, 7%-8% of them will develop a blood cancer.”

In low-risk individuals, the 10-year risk for MDS or AML is just 1%.

Dr. Weeks noted the “caveat that there are environmental factors or patient-specific issues that might increase your risk that are not considered in the calculator,” such the presence of hereditary cancer syndromes, “or if you’re getting chemotherapy for other cancers.”

From a cardiology point of view, Dr. Ballantyne said that, above all, “cardiologists need to be aware that some of these people are at increased risk for cardiovascular events.” This prompted a team including Dr. Weeks and Dr. Ballantyne to study whether the CHRS can also predict cardiovascular risk.

They found that people designated low-risk on the score faced an 8% increased risk for all-cause mortality vs individuals without CHIP during a median follow-up of 7 years. This rose to a 12% increase in intermediate-risk individuals.

And those deemed high-risk had a 2.5-fold increased risk for early mortality and a threefold higher risk for cardiovascular death.

Dr. Weeks noted: “We have not done a dedicated study to define a cardiovascular disease-specific calculator for CHIP,” but in the meantime, the CHRS is a “very reasonable way to estimate what someone’s risk of progression or adverse events is for cardiovascular disease.”

For clinicians, however, the key question becomes: What can be done to mitigate the risks, particularly in high-risk individuals?

For malignant conditions, the approach is to monitor patients, although “we and other centers are in the process of developing various interventional clinical trials to test various agents on their ability to improve blood counts, as well as to mitigate the risk of progression to overt blood cancer,” said Dr. Weeks.
 

Treat CHIP Like Lipoprotein(a)?

As for cardiovascular risk, Dr. Ballantyne believes that, because CHIP is an unmodifiable risk factor, an example to follow could be lipoprotein(a) (LP[a]).

“We don’t have a therapy specifically to target LP(a) yet, but we do know that the things that benefit in general,” he said, such as “taking a statin, lowering blood pressure into the optimal zone, diet ,and exercise.”

“What we do in our clinic, and what others have been doing,” Dr. Weeks added, “is for every patient who comes in and is diagnosed with CHIP, we are referring them to preventative cardiology for very aggressive preventative management.”

Finally, both Dr. Ballantyne and Dr. Weeks agree that there are many potential innovations on the horizon.

“It’s pretty exciting in terms of beginning to understand some of the links between aging, cardiovascular disease, and cancer that we had not been thinking about,” Dr. Ballantyne said.

On the malignant side, Dr. Weeks is already working on a prospective study to determine how the risks associated with CHIP evolve when patients undergo chemotherapy and radiation for other cancers.

“That will be really exciting and will help us to develop a specific calculator in that context,” she said, adding that a cardiovascular-specific calculator “is also coming down the line.”

Dr. Weeks declared relationships with Abbvie, Vertex, and Sobi. Dr. Ballantyne declared a relationship with Ten Sixteen Bio, and funding from the National Heart, Lung, and Blood Institute. No other relevant financial relationships were declared.
 

A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Cancers Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” wrote lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Task Force recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

• Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.
• PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.
• Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.
• For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.
• Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.
• Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” added Oh, who is also chief medical officer for the Prostate Cancer Foundation.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Garraway reported having no disclosures.
 

A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Cancers Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” wrote lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Task Force recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

• Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.
• PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.
• Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.
• For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.
• Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.
• Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” added Oh, who is also chief medical officer for the Prostate Cancer Foundation.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Garraway reported having no disclosures.
 

A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Cancers Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” wrote lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Task Force recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

• Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.
• PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.
• Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.
• For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.
• Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.
• Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” added Oh, who is also chief medical officer for the Prostate Cancer Foundation.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Garraway reported having no disclosures.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Just a day before the annual meeting of the American Academy of Dermatology (AAD) began, a study was published online in JAMA Dermatology, cautioning that most downloadable mobile apps driven by artificial intelligence (AI) for use in monitoring dermatologic conditions lack validation.

Not least of the problems among the 41 apps evaluated, the majority offered no supporting evidence, no information about whether the app performance had been validated, and no information about how user privacy would be managed, reported Shannon Wongvibulsin, MD, PhD, a resident in the dermatology program at the University of California, Los Angeles, and her coauthors.

The findings from this report were also summarized in a poster at the AAD meeting, and the major themes were reiterated in several AAD symposia devoted to AI at the meeting. Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York City, was one of those who weighed in on the future of AI. Although she was the senior author of the report, she did not address the report or poster directly, but her presentation on the practical aspects of incorporating AI into dermatology practice revisited several of its themes. 

Of the different themes, perhaps the most important were the concept that the source of AI data matters and the point that practicing clinicians should be familiar with the data source.

To date, “there is not much transparency in what data AI models are using,” Dr. Rotemberg said at the meeting. Based on the expectation that dermatologists will be purchasing rather than developing their own AI-based systems, she reiterated more than once that “transparency of data is critical,” even if vendors are often reluctant to reveal how their proprietary systems have been developed.

Few Dermatology Apps Are Vetted for Accuracy

In the poster and in the more detailed JAMA Dermatology paper, Dr. Wongvibulsin and her coinvestigators evaluated direct-to-consumer downloadable apps that claim to help with the assessment and management of skin conditions. Very few provided any supporting evidence of accuracy or even information about how they functioned.

The 41 apps were drawn from more than 300 apps; the others were excluded for failing to meet such criteria as failing to employ AI, not being available in English, or not addressing clinical management of dermatologic diseases. Dr. Wongvibulsin pointed out that none of the apps had been granted regulatory approval even though only two provided a disclaimer to that effect.

In all, just 5 of the 41 provided supporting evidence from a peer-reviewed journal, and less than 40% were created with any input from a dermatologist, Dr. Wongvibulsin reported. The result is that the utility and accuracy of these apps were, for the most part, difficult to judge.

“At a minimum, app developers should provide details on what AI algorithms are used, what data sets were used for training, testing, and validation, whether there was any clinician input, whether there are any supporting publications, how user-submitted images are used, and if there are any measures used to ensure data privacy,” Dr. Wongvibulsin wrote in the poster.

For AI-based apps or systems designed for use by dermatologists, Dr. Rotemberg made similar assertions in her overview of what clinicians should be considering for proprietary AI systems, whether to help with diagnosis or improve office efficiency.
 

Only One Dermatology App Cleared By the FDA

Currently, the only FDA-cleared app for dermatologic use is the DermaSensor, an AI-driven device. It was cleared for use in January 2024 for the evaluation of skin lesions “suggestive” of melanoma, basal cell carcinoma, and/or squamous cell carcinoma in patients aged ≥ 40 years “to assist health care providers in determining whether to refer a patient to a dermatologist,” according to an FDA announcement.

Using elastic scattering spectroscopy to analyze light reflecting off the skin to detect malignancy, the manufacturer’s promotional material claims a 96% sensitivity and a 97% specificity. 

While Dr. Rotemberg did not comment on these claims, she cautioned that AI models differ with regards to how they were trained and the relative heterogeneity of the training dataset defined by types of patients, types of skin, and types of AI learning processes. All of these variables are relevant in whether the AI will perform in a given clinical setting at the level it performed during development.

“The most accurate models employ narrow datasets, but these do not necessarily mimic what we see in practice,” she said.

In addition, even when an AI-based system is working for a given task, it must be monitored over time. Dr. Rotemberg warned about the potential for “data drift,” which describes the slow evolution in how diseases present, their prevalence by age, or other factors that might affect AI performance. She explained that repeated validation is needed to ensure that the AI-based models remain as accurate over time as they were when first used.

Many of these concepts were explored in a consensus statement from the International Skin Imaging Collaboration AI Working Group, published in JAMA Dermatology in December 2021. The statement, of which Dr. Rotemberg was a coauthor, provided recommendations for the principles of AI algorithm development specific to dermatologic considerations.

At the AAD symposium, Dr. Rotemberg asked the audience for suggestions about the needs they hoped AI might address for in office care or efficiency. Their responses included generating prior authorizations for prescriptions, triaging email for importance, and helping to improve efficiency for common front desk tasks. She liked all of these suggestions, but she warned that as powerful as it can be, AI is not likely to provide technology that will fit seamlessly into workflows without adjustment.

“Our current systems do not allow human integration of AI models,” Dr. Rotemberg said. Rather than counting on AI to adapt to current practices, she cautioned that “we may have to redesign our entire structure to actually be able to accommodate AI-based” systems. The risk for users is tasks that become more challenging before they become easier. 

AI Should Not Be a Black Box

AI is promising, but it is not magic, according to other investigators, including Tofunmi A. Omiye, PhD, a postdoctoral scholar in dermatology at Stanford University, California. First author of a recent review of AI in dermatology published in Frontiers in Medicine, Dr. Omiye agreed that clinicians who want to employ AI should be able to understand basic principles if they want the technology to perform as expected.

“I totally agree that physicians should at least have a basic understanding of the data sources for training AI models as we have found that to be important to the performance of these models in the clinical setting,” he told this news organization.

“Beyond understanding the data sources, I believe physicians can also try to have a comprehensive understanding of what AI means, its training process, and evaluation as this will help them to evaluate its utility in their practice,” he added. He also reinforced the relevance of data drift.

“Concepts like distribution shift — where models perform less well over time due to changes in the patient population — are also important to keep in mind,” Dr. Omiye said.

Dr. Wongvibulsin, Dr. Rotemberg, and Dr. Omiye reported no potential financial conflicts of interest relevant to this topic. 

A version of this article appeared on Medscape.com .

SAN DIEGO — Just a day before the annual meeting of the American Academy of Dermatology (AAD) began, a study was published online in JAMA Dermatology, cautioning that most downloadable mobile apps driven by artificial intelligence (AI) for use in monitoring dermatologic conditions lack validation.

Not least of the problems among the 41 apps evaluated, the majority offered no supporting evidence, no information about whether the app performance had been validated, and no information about how user privacy would be managed, reported Shannon Wongvibulsin, MD, PhD, a resident in the dermatology program at the University of California, Los Angeles, and her coauthors.

The findings from this report were also summarized in a poster at the AAD meeting, and the major themes were reiterated in several AAD symposia devoted to AI at the meeting. Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York City, was one of those who weighed in on the future of AI. Although she was the senior author of the report, she did not address the report or poster directly, but her presentation on the practical aspects of incorporating AI into dermatology practice revisited several of its themes. 

Of the different themes, perhaps the most important were the concept that the source of AI data matters and the point that practicing clinicians should be familiar with the data source.

To date, “there is not much transparency in what data AI models are using,” Dr. Rotemberg said at the meeting. Based on the expectation that dermatologists will be purchasing rather than developing their own AI-based systems, she reiterated more than once that “transparency of data is critical,” even if vendors are often reluctant to reveal how their proprietary systems have been developed.

Few Dermatology Apps Are Vetted for Accuracy

In the poster and in the more detailed JAMA Dermatology paper, Dr. Wongvibulsin and her coinvestigators evaluated direct-to-consumer downloadable apps that claim to help with the assessment and management of skin conditions. Very few provided any supporting evidence of accuracy or even information about how they functioned.

The 41 apps were drawn from more than 300 apps; the others were excluded for failing to meet such criteria as failing to employ AI, not being available in English, or not addressing clinical management of dermatologic diseases. Dr. Wongvibulsin pointed out that none of the apps had been granted regulatory approval even though only two provided a disclaimer to that effect.

In all, just 5 of the 41 provided supporting evidence from a peer-reviewed journal, and less than 40% were created with any input from a dermatologist, Dr. Wongvibulsin reported. The result is that the utility and accuracy of these apps were, for the most part, difficult to judge.

“At a minimum, app developers should provide details on what AI algorithms are used, what data sets were used for training, testing, and validation, whether there was any clinician input, whether there are any supporting publications, how user-submitted images are used, and if there are any measures used to ensure data privacy,” Dr. Wongvibulsin wrote in the poster.

For AI-based apps or systems designed for use by dermatologists, Dr. Rotemberg made similar assertions in her overview of what clinicians should be considering for proprietary AI systems, whether to help with diagnosis or improve office efficiency.
 

Only One Dermatology App Cleared By the FDA

Currently, the only FDA-cleared app for dermatologic use is the DermaSensor, an AI-driven device. It was cleared for use in January 2024 for the evaluation of skin lesions “suggestive” of melanoma, basal cell carcinoma, and/or squamous cell carcinoma in patients aged ≥ 40 years “to assist health care providers in determining whether to refer a patient to a dermatologist,” according to an FDA announcement.

Using elastic scattering spectroscopy to analyze light reflecting off the skin to detect malignancy, the manufacturer’s promotional material claims a 96% sensitivity and a 97% specificity. 

While Dr. Rotemberg did not comment on these claims, she cautioned that AI models differ with regards to how they were trained and the relative heterogeneity of the training dataset defined by types of patients, types of skin, and types of AI learning processes. All of these variables are relevant in whether the AI will perform in a given clinical setting at the level it performed during development.

“The most accurate models employ narrow datasets, but these do not necessarily mimic what we see in practice,” she said.

In addition, even when an AI-based system is working for a given task, it must be monitored over time. Dr. Rotemberg warned about the potential for “data drift,” which describes the slow evolution in how diseases present, their prevalence by age, or other factors that might affect AI performance. She explained that repeated validation is needed to ensure that the AI-based models remain as accurate over time as they were when first used.

Many of these concepts were explored in a consensus statement from the International Skin Imaging Collaboration AI Working Group, published in JAMA Dermatology in December 2021. The statement, of which Dr. Rotemberg was a coauthor, provided recommendations for the principles of AI algorithm development specific to dermatologic considerations.

At the AAD symposium, Dr. Rotemberg asked the audience for suggestions about the needs they hoped AI might address for in office care or efficiency. Their responses included generating prior authorizations for prescriptions, triaging email for importance, and helping to improve efficiency for common front desk tasks. She liked all of these suggestions, but she warned that as powerful as it can be, AI is not likely to provide technology that will fit seamlessly into workflows without adjustment.

“Our current systems do not allow human integration of AI models,” Dr. Rotemberg said. Rather than counting on AI to adapt to current practices, she cautioned that “we may have to redesign our entire structure to actually be able to accommodate AI-based” systems. The risk for users is tasks that become more challenging before they become easier. 

AI Should Not Be a Black Box

AI is promising, but it is not magic, according to other investigators, including Tofunmi A. Omiye, PhD, a postdoctoral scholar in dermatology at Stanford University, California. First author of a recent review of AI in dermatology published in Frontiers in Medicine, Dr. Omiye agreed that clinicians who want to employ AI should be able to understand basic principles if they want the technology to perform as expected.

“I totally agree that physicians should at least have a basic understanding of the data sources for training AI models as we have found that to be important to the performance of these models in the clinical setting,” he told this news organization.

“Beyond understanding the data sources, I believe physicians can also try to have a comprehensive understanding of what AI means, its training process, and evaluation as this will help them to evaluate its utility in their practice,” he added. He also reinforced the relevance of data drift.

“Concepts like distribution shift — where models perform less well over time due to changes in the patient population — are also important to keep in mind,” Dr. Omiye said.

Dr. Wongvibulsin, Dr. Rotemberg, and Dr. Omiye reported no potential financial conflicts of interest relevant to this topic. 

A version of this article appeared on Medscape.com .

SAN DIEGO — Just a day before the annual meeting of the American Academy of Dermatology (AAD) began, a study was published online in JAMA Dermatology, cautioning that most downloadable mobile apps driven by artificial intelligence (AI) for use in monitoring dermatologic conditions lack validation.

Not least of the problems among the 41 apps evaluated, the majority offered no supporting evidence, no information about whether the app performance had been validated, and no information about how user privacy would be managed, reported Shannon Wongvibulsin, MD, PhD, a resident in the dermatology program at the University of California, Los Angeles, and her coauthors.

The findings from this report were also summarized in a poster at the AAD meeting, and the major themes were reiterated in several AAD symposia devoted to AI at the meeting. Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York City, was one of those who weighed in on the future of AI. Although she was the senior author of the report, she did not address the report or poster directly, but her presentation on the practical aspects of incorporating AI into dermatology practice revisited several of its themes. 

Of the different themes, perhaps the most important were the concept that the source of AI data matters and the point that practicing clinicians should be familiar with the data source.

To date, “there is not much transparency in what data AI models are using,” Dr. Rotemberg said at the meeting. Based on the expectation that dermatologists will be purchasing rather than developing their own AI-based systems, she reiterated more than once that “transparency of data is critical,” even if vendors are often reluctant to reveal how their proprietary systems have been developed.

Few Dermatology Apps Are Vetted for Accuracy

In the poster and in the more detailed JAMA Dermatology paper, Dr. Wongvibulsin and her coinvestigators evaluated direct-to-consumer downloadable apps that claim to help with the assessment and management of skin conditions. Very few provided any supporting evidence of accuracy or even information about how they functioned.

The 41 apps were drawn from more than 300 apps; the others were excluded for failing to meet such criteria as failing to employ AI, not being available in English, or not addressing clinical management of dermatologic diseases. Dr. Wongvibulsin pointed out that none of the apps had been granted regulatory approval even though only two provided a disclaimer to that effect.

In all, just 5 of the 41 provided supporting evidence from a peer-reviewed journal, and less than 40% were created with any input from a dermatologist, Dr. Wongvibulsin reported. The result is that the utility and accuracy of these apps were, for the most part, difficult to judge.

“At a minimum, app developers should provide details on what AI algorithms are used, what data sets were used for training, testing, and validation, whether there was any clinician input, whether there are any supporting publications, how user-submitted images are used, and if there are any measures used to ensure data privacy,” Dr. Wongvibulsin wrote in the poster.

For AI-based apps or systems designed for use by dermatologists, Dr. Rotemberg made similar assertions in her overview of what clinicians should be considering for proprietary AI systems, whether to help with diagnosis or improve office efficiency.
 

Only One Dermatology App Cleared By the FDA

Currently, the only FDA-cleared app for dermatologic use is the DermaSensor, an AI-driven device. It was cleared for use in January 2024 for the evaluation of skin lesions “suggestive” of melanoma, basal cell carcinoma, and/or squamous cell carcinoma in patients aged ≥ 40 years “to assist health care providers in determining whether to refer a patient to a dermatologist,” according to an FDA announcement.

Using elastic scattering spectroscopy to analyze light reflecting off the skin to detect malignancy, the manufacturer’s promotional material claims a 96% sensitivity and a 97% specificity. 

While Dr. Rotemberg did not comment on these claims, she cautioned that AI models differ with regards to how they were trained and the relative heterogeneity of the training dataset defined by types of patients, types of skin, and types of AI learning processes. All of these variables are relevant in whether the AI will perform in a given clinical setting at the level it performed during development.

“The most accurate models employ narrow datasets, but these do not necessarily mimic what we see in practice,” she said.

In addition, even when an AI-based system is working for a given task, it must be monitored over time. Dr. Rotemberg warned about the potential for “data drift,” which describes the slow evolution in how diseases present, their prevalence by age, or other factors that might affect AI performance. She explained that repeated validation is needed to ensure that the AI-based models remain as accurate over time as they were when first used.

Many of these concepts were explored in a consensus statement from the International Skin Imaging Collaboration AI Working Group, published in JAMA Dermatology in December 2021. The statement, of which Dr. Rotemberg was a coauthor, provided recommendations for the principles of AI algorithm development specific to dermatologic considerations.

At the AAD symposium, Dr. Rotemberg asked the audience for suggestions about the needs they hoped AI might address for in office care or efficiency. Their responses included generating prior authorizations for prescriptions, triaging email for importance, and helping to improve efficiency for common front desk tasks. She liked all of these suggestions, but she warned that as powerful as it can be, AI is not likely to provide technology that will fit seamlessly into workflows without adjustment.

“Our current systems do not allow human integration of AI models,” Dr. Rotemberg said. Rather than counting on AI to adapt to current practices, she cautioned that “we may have to redesign our entire structure to actually be able to accommodate AI-based” systems. The risk for users is tasks that become more challenging before they become easier. 

AI Should Not Be a Black Box

AI is promising, but it is not magic, according to other investigators, including Tofunmi A. Omiye, PhD, a postdoctoral scholar in dermatology at Stanford University, California. First author of a recent review of AI in dermatology published in Frontiers in Medicine, Dr. Omiye agreed that clinicians who want to employ AI should be able to understand basic principles if they want the technology to perform as expected.

“I totally agree that physicians should at least have a basic understanding of the data sources for training AI models as we have found that to be important to the performance of these models in the clinical setting,” he told this news organization.

“Beyond understanding the data sources, I believe physicians can also try to have a comprehensive understanding of what AI means, its training process, and evaluation as this will help them to evaluate its utility in their practice,” he added. He also reinforced the relevance of data drift.

“Concepts like distribution shift — where models perform less well over time due to changes in the patient population — are also important to keep in mind,” Dr. Omiye said.

Dr. Wongvibulsin, Dr. Rotemberg, and Dr. Omiye reported no potential financial conflicts of interest relevant to this topic. 

A version of this article appeared on Medscape.com .

SAN DIEGO — Nemolizumab, the first-in-class inhibitor of interleukin-31 (IL-31), a neuroimmune cytokine linked to the promotion of pruritus and inflammation, continues to show good efficacy and safety for prurigo nodularis in an open-label follow-up pivotal trial following patients out to 52 weeks.

The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.

The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).

The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
 

New Prurigo Nodularis Therapies Needed

For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.

The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.

Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”

At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.

Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.

Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
 

No Serious AEs Over Extended Follow-Up

With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.

While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.

Itch Improves in Patients with AD

Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.

Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.

For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.

These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.

Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”

Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.

Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.

Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.

In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.

Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.

A version of this article appeared on Medscape.com.

SAN DIEGO — Nemolizumab, the first-in-class inhibitor of interleukin-31 (IL-31), a neuroimmune cytokine linked to the promotion of pruritus and inflammation, continues to show good efficacy and safety for prurigo nodularis in an open-label follow-up pivotal trial following patients out to 52 weeks.

The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.

The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).

The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
 

New Prurigo Nodularis Therapies Needed

For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.

The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.

Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”

At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.

Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.

Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
 

No Serious AEs Over Extended Follow-Up

With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.

While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.

Itch Improves in Patients with AD

Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.

Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.

For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.

These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.

Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”

Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.

Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.

Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.

In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.

Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.

A version of this article appeared on Medscape.com.

SAN DIEGO — Nemolizumab, the first-in-class inhibitor of interleukin-31 (IL-31), a neuroimmune cytokine linked to the promotion of pruritus and inflammation, continues to show good efficacy and safety for prurigo nodularis in an open-label follow-up pivotal trial following patients out to 52 weeks.

The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.

The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).

The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
 

New Prurigo Nodularis Therapies Needed

For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.

The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.

Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”

At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.

Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.

Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
 

No Serious AEs Over Extended Follow-Up

With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.

While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.

Itch Improves in Patients with AD

Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.

Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.

For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.

These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.

Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”

Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.

Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.

Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.

In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.

Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.

A version of this article appeared on Medscape.com.

Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed. 

“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.

“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added. 

The study was published online March 11, 2024, in JAMA. 
 

No Confirmatory Research

Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.

Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).

Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.

Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.

Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.

The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said. 

“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.

“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.

Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.

Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization. 

“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study. 

“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.” 

The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
 

A version of this article appeared on Medscape.com .

Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed. 

“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.

“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added. 

The study was published online March 11, 2024, in JAMA. 
 

No Confirmatory Research

Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.

Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).

Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.

Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.

Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.

The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said. 

“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.

“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.

Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.

Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization. 

“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study. 

“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.” 

The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
 

A version of this article appeared on Medscape.com .

Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed. 

“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.

“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added. 

The study was published online March 11, 2024, in JAMA. 
 

No Confirmatory Research

Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.

Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).

Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.

Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.

Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.

The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said. 

“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.

“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.

Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.

Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization. 

“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study. 

“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.” 

The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
 

A version of this article appeared on Medscape.com .